Patent Publication Number: US-2022218703-A1

Title: Fgfr inhibitors for the treatment of cancer

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims benefit of priority under 35 U.S.C. § 119(e) of U.S. Ser. No. 62/805,854, filed Feb. 14, 2019, the entire contents of which is incorporated herein by reference in its entirety. 
    
    
     INCORPORATION OF SEQUENCE LISTING 
     The material in the accompanying sequence listing is hereby incorporated by reference into this application. The accompanying sequence listing text file, name BRIDGE1100_1WO_Sequence_Listing.txt, was created on Feb. 13, 2020, and is 1084 kb. The file can be accessed using Microsoft Word on a computer that uses Windows OS. 
     FIELD 
     The present disclosure relates generally to novel fibroblast growth factor receptor (FGFR) inhibitors, and more specifically to the use of pyridinylpyrimidine-based FGFR4 specific inhibitors for the treatment of cancer. 
     BACKGROUND 
     The human family of fibroblast growth factor receptors (FGFRs) is composed of four receptor tyrosine kinases that bind 18 ligands called fibroblast growth factors (FGFs). The four members (FGFR1, FGFR2, FGFR3, and FGFR4) are highly conserved among each other and consist of extracellular ligand-binding domains, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Upon binding of ligands to the extracellular domains of FGFRs, the kinase domains are activated by autophosphorylation and then phosphorylate cytoplasmic substrates, triggering downstream signaling cascades that control cell growth and differentiation. 
     The FGFR signaling pathway is an important and validated target for cancer therapeutics since it plays a crucial role in tumor proliferation, angiogenesis, migration, and survival. Mutations and overexpression of FGFRs and their ligands have been reported in several cancers, such as breast, lung, bladder, prostate, and gastric. For instance, amplification of FGFR1 has been found in about 10% of breast cancers (predominantly in estrogen receptor positive diseases), in 10-20% of squamous non-small-cell lung cancer (NSCLC), ovarian cancer (˜5%), and bladder cancer (3%). FGFR2 amplification has been detected in gastric (5-10%) and breast cancers (4% of triple negative cases), and mutations in FGFR2 occur in 12% of endometrial carcinomas. FGFR3 mutations were identified in about 70% of non-muscle-invasive bladder cancers and 10-20% of invasive high-grade bladder cancers. Amplification and activating mutations in FGFR4 have been described in 8% of rhabdomyosarcoma patients. In addition, many preclinical studies have reported FGFR4 overexpression in prostate, colon, and liver cancers. 
     A number of FGFR small-molecule inhibitors have been developed and evaluated in clinical trials for the treatment of cancers, but most of them are pan-FGFR inhibitors with promiscuous kinome activity, such as BGJ398 and LY-2874455. It has been found, from sequence analysis, that FGFR4 contains a cysteine (Cys552) located near the ATP-binding site, in the hinge region of the receptor, which is unique within the FGFR family and rare among other kinases. In fact, the first selective FGFR4 inhibitor, BLU9931, was discovered recently targeting this unique cysteine and exhibited very good specificity and significant antitumor activity against hepatocellular carcinoma in vivo. However, the potency and bioavailability of BLU9931 is suboptimal for clinical applications. 
     SUMMARY 
     Embodiments of the present disclosure include novel pyridinylpyrimidine-based compounds that are potent FGFR4 specific inhibitors. The FGFR4 specific inhibitors can be used as targeted therapies to treat cancer. 
     In some embodiments, the present disclosure provides a compound of Formula (I) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate, or pharmaceutically acceptable salt thereof. 
     In some embodiments, each R 1 , R 2 , R 3 , R 4 , and R 5  can be independently H, F, Cl, Br, C 1-4  alkyl, cyclopropyl, N 3 , NH 2 , NO 2 , CF 3 , OCF 3 , OCHF 2 , or OC 1-4 alkyl. In some embodiments, R 6  can be (CH 2 ) 0-5 CH═CH 2 , (CH 2 ) 0-5 C≡CH, NHCO(CH 2 ) 0-5 CH═CH 2 , NH(CH 2 ) 0-5 CH═CH 2 , OCO(CH 2 ) 0-5 CH═CH 2 , O(CH 2 ) 0-5 CH═CH 2 , NHCO(CH 2 ) 0-5 C≡CH, or OCO(CH 2 ) 0-5 C≡CH. 
     In some embodiments, Linker can be selected from the group consisting of C 1-20 alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     phenyl, naphthyl, anthracene, 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , NO 2 , —NR 7 —(CH 2 ) n —R 8 , —CO NR 7 —(CH 2 ) n —R 8 , —CO—(CH 2 ) n —R 8 , —OCO—(CH 2 ) n —R 8 , and —O—(CH 2 ) n —R 8 . 
     In some embodiments, n can be an integer selected from 0 to 5. In some embodiments, R 7  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. 
     In some embodiments, R 8  can be selected from the group consisting of C 1-20  alkyl COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . 
     The present disclosure also provides a compound of Formula (II) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate, or pharmaceutically acceptable salt thereof. 
     In some embodiments, R 1  can be (CH 2 ) 0-5 CH═CH 2 , (CH 2 ) 0-5 C≡CH, NHCO(CH 2 ) 0-5 CH═CH 2 , NH(CH 2 ) 0-5 CH═CH 2 , OCO(CH 2 ) 0-5 CH═CH 2 , O(CH 2 ) 0-5 CH═CH 2 , NHCO(CH 2 ) 0-5 C≡CH, or OCO(CH 2 ) 0-5 C≡CH. 
     Linker can be selected from the group consisting of C 1-20 alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     phenyl, naphthyl, anthracene, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , NO 2 , —NR 2 —(CH 2 ) n —R 3 , —CO NR 2 —(CH 2 ) n —R 3 , —CO—(CH 2 ) n —R 3 , —OCO—(CH 2 ) n —R 3 , and —O—(CH 2 ) n —R 3 . 
     In some embodiments, R 2  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. n is an integer selected from 0 to 5. 
     In some embodiments, R 3  can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . 
     The present disclosure also provides a compound of Formula (III) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate, or pharmaceutically acceptable salt thereof. 
     In some embodiments, each R 1 , R 2 , R 3 , R 4 , and R 5  can be independently selected from the group consisting of H, F, Cl, Br, C 1-4  alkyl, cyclopropyl, N 3 , NH 2 , NO 2 , CF 3 , OCF 3 , OCHF 2 , and OC 1-4 alkyl. n can be an integer selected from 0 to 5. 
     In some embodiments, R 6  can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . R 7  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. 
     In some embodiments, the compound can selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     In some embodiments, the compound can be selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     The present disclosure also provides a pharmaceutical formulation including the compound according to Formula (I), Formula (II), Formula (III), or an optically pure stereoisomer or pharmaceutically acceptable salt thereof. The present disclosure further provides a method for treating cancer in a subject including administering a compound with the structure of Formula (I), Formula (II), Formula (III), or an optically pure stereoisomer or pharmaceutically acceptable salt thereof to the subject. In some embodiments, the compound targets amino acid residue 484 of SEQ ID NO: 52, amino acid residue 512 of SEQ ID NO: 56, or amino acid residue 552 of SEQ ID NO: 50 or 54. The present disclosure also provides a method of inhibiting a kinase activity including contacting a cell with a compound with the structure of Formula (I), Formula (II), Formula (III), or an optically pure stereoisomer or pharmaceutically acceptable salt thereof. In some embodiments, the kinase can be Anaplastic lymphoma kinase (ALK), Epidermal growth factor receptor (EGFR), Ephrin type-3 receptor 3 (EPH-B3), Focal adhesion kinase (FAK), Fibroblast growth factor receptor 1 (FGFR1), Fibroblast growth factor receptor 2 (FGFR2), Fibroblast growth factor receptor 3 (FGFR3), Fibroblast growth factor receptor 4 (FGFR4), Mast/stem cell growth factor receptor (SCFR or KIT), Mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), Hepatocyte growth factor receptor (HGFR or MET), Platelet-derived growth factor receptor alpha (PDGFRA), Platelet-derived growth factor receptor beta (PDGFRB), Proto-oncogene tyrosine kinase receptor (RET), Proto-oncogene tyrosine-protein kinase (ROS) or Tyrosine-protein kinase receptor (TYRO 3). The cell can be a cancer cell. The cancer cell can be a breast, lung, bladder, prostate, ovarian, endometrial, rhabdomyosarcoma, liver or gastric cancer cell. 
     Other features and advantages can become apparent from the following detailed drawings and description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In order to facilitate a full understanding of the present disclosure, reference is now made to the accompanying drawings, in which like elements are referenced with like numerals. These drawings should not be construed as limiting the present disclosure, but are intended to be illustrative only. The drawings are not necessarily to scale, or inclusive of all elements of a system, emphasis instead generally being placed upon illustrating the concepts, structures, and techniques sought to be protected herein. 
         FIG. 1  is a schematic representation of FGFR kinases. A. Schematic representation of the selective inhibition of FGFRs by electrophilic inhibitors by covalently targeting a thiol group (SH) in the cysteine residue. B. Partial sequence alignment of FGFR kinases within the subdomain V highliting the unique cysteine residue that FGFR4 contains near the ATP-binding site; 
         FIG. 2A  is the pharmacokinetic data of compound 1 administered by intraperitoneal injection (IP) into mice at 10 mg/kg, according to some embodiments of the present disclosure; 
         FIG. 2B  is the pharmacokinetic data of compound 1 administered by intravenous injection (IV) into mice at 1 mg/kg and per os (PO) at 5 mg/kg, according to some embodiments of the present disclosure; 
         FIG. 3A  is the mean plasma concentration time profile of compound 5 by IP administration in female CD-1 mice at 10 mg/kg, according to some embodiments of the present disclosure; and 
         FIG. 3B  is the pharmacokinetic data of compound 5 by IV administration at 5 mg/kg and PO administration at 100 mg/kg, according to some embodiments of the present disclosure. 
     
    
    
     DESCRIPTION 
     Disclosed herein is a class of chemical compounds as FGFR4-selective inhibitors. These small molecule inhibitors can be used as targeted therapies to treat cancer. 
     Fibroblast growth factor receptors (FGFRs) are highly conserved receptors consisting of extracellular ligand-binding domain, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. The human FRFR family includes four members, FGFR1, FGFR2, FGFR3, and FGFR4, which can be bound by 18 different ligands called fibroblast growth factors (FGFs). Each receptor is composed of an extracellular domain, consisting of three immunoglobulin-like domain (IgI IgII, and IgIII) and an acid box, the IgII and IgIII domains constituting the FGF ligand-binding site; a transmembrane domain; and a tyrosine kinase cytoplasmic domain. FGFRs also contain hinge region (subdomain V), located near the ATP-binding site (SEQ ID NOs 57-60). FGFRs encoding mRNA are subjected to alternative splicing, giving rise to several protein-coding splice variants or isoforms (SEQ ID NOs: 1; 3; 5; 7; 9; 11; 13; 15; 17; 19; 21; 23; 25; 27; 29; 31; 33; 35; 37; 39; 41; 43; 45; 47; 49; 51; 53; and 55). As shown in Table 3, the human FGFR1 gene encodes 9 protein coding splice variants (SEQ ID Nos: 2; 4; 6; 8; 10; 12; 14; 16; and 18), the human FGFR2 gene encodes 11 protein coding splice variants (SEQ ID Nos: 20; 22; 24; 26; 28; 30; 32; 34; 36; 38; and 40), the human FGFR3 gene encodes four protein coding splice variants (SEQ ID Nos: 42; 44; 46; and 48), and the human FGFR4 gene encodes four protein coding splice variants (SEQ ID Nos: 50; 52; 54; and 56). 
     There are 18 members in the FGF family of ligands (FGF1-FGF10 and FGF16-FGF23). The binding of a ligand to the extracellular domain of a FGFR leads to receptor dimerization resulting in the activation of the tyrosine-kinase domain by auto-phosphorylation. Subsequently, an activated FGFR phosphorylates cytoplasmic substrates, such as FGFR substrate 2 (FRS2) and phosphlypase Cγ (PLCγ) triggering downstream signaling cascades. Activated FRS2 promotes the RAS-mitogen-activated protein kinase (MAPK) or the phosphoinositide 3-kinase (PI3K)-AKT pathways that regulate cell proliferation, differentiation and survival. On the other hand, the activation of PLCγ lead to calcium release and regulates events that mediate cell motility. 
     Deregulation of FGFR signaling has been linked to oncogenesis through several mechanisms including activating mutations, gene amplification or changes in post-transcriptional processing, and translocation, leading to constitutive activation of the receptor. 
     Specifically, FGFR4 amplification and activating mutations have been described in patients with rhabdomyosarcoma, and FGFR4 overexpression have been linked to prostate, colon, breast and liver cancers. FGFR4 differs from the other FGFRs by the presence of a cysteine in the hinge region, which is unique within the FGFR family and rare among other kinases. Depending on the isoform, the cysteine is located at different positions: Cys484 of SEQ ID NO: 52, Cys512 of SEQ ID NO: 56, or Cys552 of SEQ ID NO: 50 or 54. This unique cysteine can be targeted for the design of FGFR4 specific inhibitors exhibiting very good specificity. 
     As used herein, the term “FGFR inhibitor” or “FGFRi” refers to any compound capable of inhibiting the enzymatic of FGFR, including its own auto-phosphorylation and the kinase activity. Such inhibitors efficiently inhibit FGFRs, and are said to “inhibit”, “decrease”, or “reduce” the biological activity of FGFRs. The FGFR inhibitors of the disclosure can be “pan-inhibitor” and present a broad efficiency at inhibiting one or more of FGFR1-FGFR4, or present a specific efficiency at inhibiting only one FGFR, FGFR4 for example. 
     The efficiency of a compound can be referred to by its IC50 value. The “IC50” is the half-maximal inhibitory concentration (IC50) of a compound. As used herein, the IC50 of a FGFRi refers to the concentration of inhibitor which is sufficient to induce the inhibition of the enzymatic activity of FGFR halfway between the baseline and maximum after a specified exposure time. The IC50 value of the present disclosure specifically refers to the concentration of FGFR inhibitor which is sufficient to induce the inhibition of one or more FGFRs, i.e. FGFR1, FGFR2, FGFR3 and/or FGFR4. 
     In some embodiments, the present disclosure provides a compound of Formula (I) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate, or pharmaceutically acceptable salt thereof. 
     In some embodiments, each R 1 , R 2 , R 3 , R 4 , and R 5  can be independently H, F, Cl, Br, C 1-4  alkyl, cyclopropyl, N 3 , NH 2 , NO 2 , CF 3 , OCF 3 , OCHF 2 , or OC 1-4 alkyl. In some embodiments, R 6  can be (CH 2 ) 0-5 CH═CH 2 , (CH 2 ) 0-5 C≡CH, NHCO(CH 2 ) 0-5 CH═CH 2 , NH(CH 2 ) 0-5 CH═CH 2 , OCO(CH 2 ) 0-5 CH═CH 2 , O(CH 2 ) 0-5 CH═CH 2 , NHCO(CH 2 ) 0-5 C≡CH, or OCO(CH 2 ) 0-5 C≡CH. 
     In some embodiments, Linker can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     phenyl, naphthyl, anthracene, 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF NO 2 , —NR 7 —(CH 2 ) n —R 8 , —CO NR 7 —(CH 2 ) n —R 8 , —CO—(CH 2 ) n —R 8 , —OCO—(CH 2 ) n —R 8 , and —O—(CH 2 ) n —R 8 . The number of the optional substituents can be an interger selected from 0 to 4. 
     In some embodiments, n can be an integer selected from 0 to 5. In some embodiments, R 7  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. 
     In some embodiments, R 8  can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . 
     In some embodiments, R 1  and R 5  are Cl, R 2  and R 4  are OMe, and R 3  is H. 
     The present disclosure also provides a compound of Formula (II) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate, or pharmaceutically acceptable salt thereof. 
     In some embodiments, R 1  can be (CH 2 ) 0-5 CH═CH 2 , (CH 2 ) 0-5 C≡CH, NHCO(CH 2 ) 0-5 CH═CH 2 , NH(CH 2 ) 0-5 CH═CH 2 , OCO(CH 2 ) 0-5 CH═CH 2 , O(CH 2 ) 0-5 CH═CH 2 , NHCO(CH 2 ) 0-5 C≡CH, or OCO(CH 2 ) 0-5 C≡CH. 
     Linker can be selected from the group consisting of C 1-20 alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     phenyl, naphthyl, anthracene, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , NO 2 , —NR 2 —(CH 2 ) n —R 3 , —CO NR 2 —(CH 2 ) n —R 3 , —CO—(CH 2 ) n —R 3 , —OCO—(CH 2 ) n —R 3 , and —O—(CH 2 ) n —R 3 . The number of the optional substituents can be an interger selected from 0 to 4. 
     In some embodiments, R 2  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. n is an integer selected from 0 to 5. 
     In some embodiments, R 3  can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . 
     The present disclosure also provides a compound of Formula (III) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate or pharmaceutically acceptable salt thereof. 
     In some embodiments, each R 1 , R 2 , R 3 , R 4 , and R 5  can be independently selected from the group consisting of H, F, Cl, Br, C 1-4  alkyl, cyclopropyl, N 3 , NH 2 , NO 2 , CF 3 , OCF 3 , OCHF 2 , and OC 1-4 alkyl. n can be an integer selected from 0 to 5. 
     In some embodiments, R 6  can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . R 7  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. The number of the optional substituents can be an interger selected from 0 to 4. 
     In some embodiments, R 1  and R 5  are Cl, R 2  and R 4  are OMe, and R 3  is H. 
     In some embodiments, the present disclosure provides a compound of Formula (IV) 
     
       
         
         
             
             
         
       
     
     or an optically pure stereoisomer, solvate, or pharmaceutically acceptable salt thereof. 
     In some embodiments, each R 1 , R 2 , R 3 , R 4 , and R 5  can be independently H, F, Cl, Br, C 1-4  alkyl, cyclopropyl, N 3 , NH 2 , NO 2 , CF 3 , OCF 3 , OCHF 2 , or OC 1-4 alkyl. In some embodiments, R 6  can be (CH 2 ) 0-5 CH═CH 2 , (CH 2 ) 0-5 C≡CH, NHCO(CH 2 ) 0-5 CH═CH 2 , NH(CH 2 ) 0-5 CH═CH 2 , OCO(CH 2 ) 0-5 CH═CH 2 , O(CH 2 ) 0-5 CH═CH 2 , NHCO(CH 2 ) 0-5 C≡CH, or OCO(CH 2 ) 0-5 C≡CH. 
     In some embodiments, each A and B can be independently NR 7 , CONR 7 , O, CO, or OCO. 
     In some embodiments, Core can be selected from the group consisting of 
     
       
         
         
             
             
         
       
     
     Each D can be independently N or CH. 
     In some embodiments, Linker can be selected from the group consisting of C 1-20  alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     phenyl, naphthyl, anthracene, 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , NO 2 , —NR 7 —(CH 2 ) n —R 8 , —CO NR 7 —(CH 2 ) n —R 8 , —CO—(CH 2 ) n —R 8 , —OCO—(CH 2 ) n —R 8 , and —O—(CH 2 ) n —R 8 . The number of the optional substituents can be an interger selected from 0 to 4. 
     In some embodiments, n can be an integer selected from 0 to 5. In some embodiments, R 7  can be selected from the group consisting of H, C 1-4  alkyl, and COC 1-4 alkyl. 
     In some embodiments, R 8  can be selected from the group consisting of C 1-20 alkyl, COC 1-20 alkyl, CO 2 C 1-20 alkyl, 
     
       
         
         
             
             
         
       
     
     optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, C 1-4  alkyl, CF 3 , CHF 2 , and NO 2 . 
     In some embodiments, the compound of the present disclosure is selected from the group consisting of compound 1-4 and 6-16 as shown in Table 1. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 The FGFR inhibitor compounds in the present disclosure. 
               
            
           
           
               
               
            
               
                 Compound Number 
                 Chemical Structure 
               
               
                   
               
               
                 compound 1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 compound 16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
         
       
     
     The present disclosure also provides a pharmaceutical formulation including the compound according to Formula (I), Formula (II), Formula (III), or an optically pure stereoisomer or pharmaceutically acceptable salt thereof. The present disclosure further provides a method for treating cancer in a subject including administering a compound with the structure of Formula (I), Formula (II), Formula (III), or an optically pure stereoisomer or pharmaceutically acceptable salt thereof to the subject. The present disclosure also provides a method of inhibiting a kinase activity including contacting a cell with a compound with the structure of Formula (I), Formula (II), Formula (III), or an optically pure stereoisomer or pharmaceutically acceptable salt thereof. In some embodiments, the kinase can be Anaplastic lymphoma kinase (ALK), Epidermal growth factor receptor (EGFR), Ephrin type-3 receptor 3 (EPH-B3), Focal adhesion kinase (FAK), Fibroblast growth factor receptor 1 (FGFR1), Fibroblast growth factor receptor 2 (FGFR2), Fibroblast growth factor receptor 3 (FGFR3), Fibroblast growth factor receptor 4 (FGFR4), Mast/stem cell growth factor receptor (SCFR or KIT), Mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), Hepatocyte growth factor receptor (HGFR or MET), Platelet-derived growth factor receptor alpha (PDGFRA), Platelet-derived growth factor receptor beta (PDGFRB), Proto-oncogene tyrosine kinase receptor (RET), Proto-oncogene tyrosine-protein kinase (ROS) or Tyrosine-protein kinase receptor (TYRO 3). The cell can be a cancer cell. The cancer cell can be a breast, lung, bladder, prostate, ovarian, endometrial, rhabdomyosarcoma, liver or gastric cancer cell. 
     The present disclosure specifically provides compounds with non-obvious property improvement compared to control structures such as compound 5 with the structure of 
     
       
         
         
             
             
         
       
     
     The IUPAC name of the compound is N-(2-((6-(2-((2,6-dichloro-3,5-dimethoxyphenyl)amino)pyridin-3-yl)pyrimidin-4-yl)amino)-3-methylphenyl)acrylamide. 
     The term “about” will be understood by persons of ordinary skill in the art. Whether the term “about” is used explicitly or not, every quantity given herein refers to the actual given value, and it is also meant to refer to the approximation to such given value that would be reasonably inferred based on the ordinary skill in the art. 
     Alkyl groups refer to univalent groups derived from alkanes by removal of a hydrogen atom from any carbon atom, which include straight chain and branched chain with from 1 to 12 carbon atoms, and typically from 1 to about 10 carbons or in some embodiments, from 1 to about 6 carbon atoms, or in other embodiments having 1, 2, 3 or 4 carbon atoms. Examples of straight chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl groups. Examples of branched chain alkyl groups include, but are not limited to isopropyl, isobutyl, sec-butyl and tert-butyl groups. Alkyl groups may be substituted or unsubstituted. Representative substituted alkyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di-, or tri-substituted. As used herein, the term alkyl, unless otherwise stated, refers to both cyclic and noncyclic groups. 
     The terms “cyclic alkyl” or “cycloalkyl” refer to univalent groups derived from cycloalkanes by removal of a hydrogen atom from a ring carbon atom. Cycloalkyl groups are saturated or partially saturated non-aromatic structures with a single ring or multiple rings including isolated, fused, bridged, and spiro ring systems, having 3 to 14 carbon atoms, or in some embodiments, from 3 to 12, or 3 to 10, or 3 to 8, or 3, 4, 5, 6 or 7 carbon atoms. Cycloalkyl groups may be substituted or unsubstituted. Representative substituted cycloalkyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di-, or tri-substituted. Examples of monocyclic cycloalkyl groups include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups. Examples of multi-cyclic ring systems include, but are not limited to, bicycle[4.4.0]decane, bicycle[2.2.1]heptane, spiro[2.2]pentane, and the like. 
     Alkenyl groups refer to straight and branched chain and cycloalkyl groups as defined above, with one or more double bonds between two carbon atoms. Alkenyl groups may have 2 to about 12 carbon atoms, or in some embodiment from 1 to about 10 carbons or in other embodiments, from 1 to about 6 carbon atoms, or 1, 2, 3 or 4 carbon atoms in other embodiments. Alkenyl groups may be substituted or unsubstituted. Representative substituted alkenyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di-, or tri-substituted. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, —CH═CH(CH 3 ), —CH═C(CH 3 ) 2 , —C(CH 3 )═CH 2 , cyclopentenyl, cyclohexenyl, butadienyl, pentadienyl, and hexadienyl, among others. 
     Alkynyl groups refer to straight and branched chain and cycloalkyl groups as defined above, with one or more triple bonds between two carbon atoms. Alkynyl groups may have 2 to about 12 carbon atoms, or in some embodiment from 1 to about 10 carbons or in other embodiments, from 1 to about 6 carbon atoms, or 1, 2, 3 or 4 carbon atoms in other embodiments. Alkynyl groups may be substituted or unsubstituted. Representative substituted alkynyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di-, or tri-substituted. Exemplary alkynyl groups include, but are not limited to, ethynyl, propargyl, and —C≡C(CH 3 ), among others. 
     Aryl groups are cyclic aromatic hydrocarbons that include single and multiple ring compounds, including multiple ring compounds that contain separate and/or fused aryl groups. Aryl groups may contain from 6 to about 18 ring carbons, or in some embodiments from 6 to 14 ring carbons or even 6 to 10 ring carbons in other embodiments. Aryl group also includes heteroaryl groups, which are aromatic ring compounds containing 5 or more ring members, one or more ring carbon atoms of which are replaced with heteroatom such as, but not limited to, N, O, and S. Aryl groups may be substituted or unsubstituted. Representative substituted aryl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di-, or tri-substituted. Aryl groups include, but are not limited to, phenyl, biphenylenyl, triphenylenyl, naphthyl, anthryl, and pyrenyl groups. 
     Suitable heterocyclyl groups include cyclic groups with atoms of at least two different elements as members of its rings, of which one or more is a heteroatom such as, but not limited to, N, O, or S. Heterocyclyl groups may include 3 to about 20 ring members, or 3 to 18 in some embodiments, or about 3 to 15, 3 to 12, 3 to 10, or 3 to 6 ring members. The ring systems in heterocyclyl groups may be unsaturated, partially saturated, and/or saturated. Heterocyclyl groups may be substituted or unsubstituted. Representative substituted heterocyclyl groups may be mono-substituted or substituted more than once, such as, but not limited to, mono-, di-, or tri-substituted. Exemplary heterocyclyl groups include, but are not limited to, pyrrolidinyl, tetrahydrofuryl, dihydrofuryl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, azetidinyl, aziridinyl, imidazolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydrofuranyl, dioxolyl, furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl, oxetanyl, thietanyl, homopiperidyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6-tetrahydropyridyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxolanyl, dioxanyl, purinyl, quinolizinyl, cinnolinyl, phthalazinyl, pteridinyl, and benzothiazolyl groups. 
     Polycyclic or polycyclyl groups refer to two or more rings in which two or more carbons are common to the two adjoining rings, wherein the rings are “fused rings”; if the rings are joined by one common carbon atom, these are “spiro” ring systems. Rings that are joined through non-adjacent atoms are “bridged” rings. Polycyclic groups may be substituted or unsubstituted. Representative polycyclic groups may be substituted one or more times. 
     Halogen groups include F, Cl, Br, and I; nitro group refers to —NO 2 ; cyano group refers to —CN; isocyano group refers to —N≡C; epoxy groups encompass structures in which an oxygen atom is directly attached to two adjacent or non-adjacent carbon atoms of a carbon chain or ring system, which is essentially a cyclic ether structure. An epoxide is a cyclic ether with a three-atom ring. 
     An alkoxy group is a substituted or unsubstituted alkyl group, as defined above, singular bonded to oxygen. Alkoxy groups may be substituted or unsubstituted. Representative substituted alkoxy groups may be substituted one or more times. Exemplary alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, isopropoxy, sec-butoxy, tert-butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, and cyclohexyloxy groups. 
     The terms “amine” and “amino” refer to derivatives of ammonia, wherein one of more hydrogen atoms have been replaced by a substituent which include, but are not limited to alkyl, alkenyl, aryl, and heterocyclyl groups. Carbamate groups refers to —O(C═O)NR 1 R 2 , where R 1  and R 2  are independently hydrogen, aliphatic groups, aryl groups, or heterocyclyl groups. 
     The term “optionally substituted” means the anteceding group may be substituted or unsubstituted. When substituted, the substituents of an “optionally substituted” group may include, without limitation, one or more substituents independently selected from the following groups or a particular designated set of groups, alone or in combination: lower alkyl, lower alkenyl, lower alkynyl, lower alkanoyl, lower heteroalkyl, lower heterocycloalkyl, lower haloalkyl, lower haloalkenyl, lower haloalkynyl, lower perhaloalkyl, lower perhaloalkoxy, lower cycloalkyl, phenyl, aryl, aryloxy, lower alkoxy, lower haloalkoxy, oxo, lower acyloxy, carbonyl, carboxyl, lower alkylcarbonyl, lower carboxyester, lower carboxamido, cyano, hydrogen, halogen, hydroxy, amino, lower alkylamino, arylamino, amido, nitro, thiol, lower alkylthio, lower haloalkylthio, lower perhaloalkylthio, arylthio, sulfonate, sulfonic acid, trisubstituted silyl, N 3 , SH, SCH 3 , C(O)CH 3 , CO 2 CH 3 , CO 2 H, pyridinyl, thiophene, furanyl, lower carbamate, and lower urea. Two substituents may be joined together to form a fused five-, six-, or seven-membered carbocyclic or heterocyclic ring consisting of zero to three heteroatoms, for example forming methylenedioxy or ethylenedioxy. An optionally substituted group may be unsubstituted (e.g., —CH 2 CH 3 ), fully substituted (e.g., —CF 2 CF 3 ), monosubstituted (e.g., —CH 2 CH 2 F) or substituted at a level anywhere in-between fully substituted and monosubstituted (e.g., —CH 2 CF 3 ). Where substituents are recited without qualification as to substitution, both substituted and unsubstituted forms are encompassed. Where a substituent is qualified as “substituted,” the substituted form is specifically intended. Additionally, different sets of optional substituents to a particular moiety may be defined as needed; in these cases, the optional substitution will be as defined, often immediately following the phrase, “optionally substituted with.” 
     Pharmaceutically acceptable salts of compounds described herein include conventional nontoxic salts or quaternary ammonium salts of a compound, e.g., from non-toxic organic or inorganic acids. For example, such conventional nontoxic salts include those derived from inorganic acids such as hydrochloride, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmitic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicyclic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isothionic, and the like. In other cases, described compounds may contain one or more acidic functional groups and, thus, are capable of forming pharmaceutically acceptable salts with pharmaceutically acceptable bases. These salts can likewise be prepared in situ in the administration vehicle or the dosage form manufacturing process, or by separately reacting the purified compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. 
     The term “treatment” is used interchangeably herein with the term “therapeutic method” and refers to both 1) therapeutic treatments or measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic conditions, disease or disorder, and 2) and prophylactic/preventative measures. Those in need of treatment may include individuals already having a particular medical disease or disorder as well as those who may ultimately acquire the disorder (i.e., those needing preventive measures). 
     The term “subject” as used herein refers to any individual or patient to which the subject methods are performed. Generally, the subject is human, although as will be appreciated by those in the art, the subject may be an animal. 
     The terms “therapeutically effective amount”, “effective dose”, “therapeutically effective dose”, “effective amount,” or the like refer to the amount of a subject compound that will elicit the biological or medical response in a tissue, system, animal or human that is being sought by administering said compound. Generally, the response is either amelioration of symptoms in a patient or a desired biological outcome. Such amount should be sufficient to inhibit FGFR enzymatic activity. 
     Also disclosed herein are pharmaceutical compositions including compounds with the structures of Formula (I), Formula (II), or Formula (III). The term “pharmaceutically acceptable carrier” refers to a non-toxic carrier that may be administered to a patient, together with a compound of this disclosure, and which does not destroy the pharmacological activity thereof. Pharmaceutically acceptable carriers that may be used in these compositions include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. 
     Pharmaceutically acceptable carriers that may be used in the pharmaceutical compositions of this disclosure include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, wool fat and self-emulsifying drug delivery systems (SEDDS) such as α-tocopherol, polyethyleneglycol 1000 succinate, or other similar polymeric delivery matrices. 
     In pharmaceutical composition comprising only the compounds described herein as the active component, methods for administering these compositions may additionally comprise the step of administering to the subject an additional agent or therapy. Such therapies include, but are not limited to, an anemia therapy, a diabetes therapy, a hypertension therapy, a cholesterol therapy, neuropharmacologic drugs, drugs modulating cardiovascular function, drugs modulating inflammation, immune function, production of blood cells; hormones and antagonists, drugs affecting gastrointestinal function, chemotherapeutics of microbial diseases, and/or chemotherapeutics of neoplastic disease. Other pharmacological therapies can include any other drug or biologic found in any drug class. For example, other drug classes can comprise allergy/cold/ENT therapies, analgesics, anesthetics, anti-inflammatories, antimicrobials, antivirals, asthma/pulmonary therapies, cardiovascular therapies, dermatology therapies, endocrine/metabolic therapies, gastrointestinal therapies, cancer therapies, immunology therapies, neurologic therapies, ophthalmic therapies, psychiatric therapies or rheumatologic therapies. Other examples of agents or therapies that can be administered with the compounds described herein include a matrix metalloprotease inhibitor, a lipoxygenase inhibitor, a cytokine antagonist, an immunosuppressant, a cytokine, a growth factor, an immunomodulator, a prostaglandin or an anti-vascular hyperproliferation compound. 
     The term “therapeutically effective amount” as used herein refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes one or more of the following: (1) Preventing the disease; for example, preventing a disease, condition or disorder in an individual that may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease, (2) Inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual that is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and/or symptomatology), and (3) Ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual that is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and/or symptomatology). 
     The compounds of this disclosure may be employed in a conventional manner for controlling the disease described herein, including, but not limited to, cancer. Such methods of treatment, their dosage levels and requirements may be selected by those of ordinary skill in the art from available methods and techniques. For example, the compounds of this disclosure may be combined with a pharmaceutically acceptable adjuvant for administration to a patient suffering from cancer in a pharmaceutically acceptable manner and in an amount effective to treat cancer. 
     Alternatively, the compounds of this disclosure may be used in compositions and methods for treating or protecting individuals against the diseases described herein, including but not limited to a cancer, over extended periods of time. The compounds may be employed in such compositions either alone or together with other compounds of this disclosure in a manner consistent with the conventional utilization of such compounds in pharmaceutical compositions. For example, a compound of this disclosure may be combined with pharmaceutically acceptable adjuvants conventionally employed in vaccines and administered in prophylactically effective amounts to protect individuals over an extended period of time against the diseases described herein, including, but not limited to, cancer. 
     As used herein, the terms “combination,” “combined,” and related terms refer to the simultaneous or sequential administration of therapeutic agents in accordance with this disclosure. For example, a described compound may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present disclosure provides a single unit dosage form comprising a described compound, an additional therapeutic agent, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. Two or more agents are typically considered to be administered “in combination” when a patient or individual is simultaneously exposed to both agents. In many embodiments, two or more agents are considered to be administered “in combination” when a patient or individual simultaneously shows therapeutically relevant levels of the agents in a particular target tissue or sample (e.g., in brain, in serum, etc.). 
     When the compounds of this disclosure are administered in combination therapies with other agents, they may be administered sequentially or concurrently to the patient. Alternatively, pharmaceutical or prophylactic compositions according to this disclosure comprise a combination of ivermectin, or any other compound described herein, and another therapeutic or prophylactic agent. Additional therapeutic agents that are normally administered to treat a particular disease or condition may be referred to as “agents appropriate for the disease, or condition, being treated.” 
     The compounds utilized in the compositions and methods of this disclosure may also be modified by appending appropriate functionalities to enhance selective biological properties. Such modifications are known in the art and include those, which increase biological penetration into a given biological system (e.g., blood, lymphatic system, or central nervous system), increase oral availability, increase solubility to allow administration by injection, alter metabolism and/or alter rate of excretion. 
     According to a preferred embodiment, the compositions of this disclosure are formulated for pharmaceutical administration to a subject or patient, e.g., a mammal, preferably a human being. Such pharmaceutical compositions are used to ameliorate, treat or prevent any of the diseases described herein including but not limited to cancer in a subject. 
     Agents of the disclosure are often administered as pharmaceutical compositions comprising an active therapeutic agent, i.e., and a variety of other pharmaceutically acceptable components. See Remington&#39;s Pharmaceutical Science (15th ed., Mack Publishing Company, Easton, Pa., 1980). The preferred form depends on the intended mode of administration and therapeutic application. The compositions can also include, depending on the formulation desired, pharmaceutically acceptable, non-toxic carriers or diluents, which are defined as vehicles commonly used to formulate pharmaceutical compositions for animal or human administration. The diluent is selected so as not to affect the biological activity of the combination. Examples of such diluents are distilled water, physiological phosphate-buffered saline, Ringer&#39;s solutions, dextrose solution, and Hank&#39;s solution. In addition, the pharmaceutical composition or formulation may also include other carriers, adjuvants, or nontoxic, nontherapeutic, nonimmunogenic stabilizers and the like. 
     In some embodiments, the present disclosure provides pharmaceutically acceptable compositions comprising a therapeutically effective amount of one or more of a described compound, formulated together with one or more pharmaceutically acceptable carriers (additives) and/or diluents for use in treating the diseases described herein, including, but not limited to cancer. While it is possible for a described compound to be administered alone, it is preferable to administer a described compound as a pharmaceutical formulation (composition) as described herein. Described compounds may be formulated for administration in any convenient way for use in human or veterinary medicine, by analogy with other pharmaceuticals. 
     As described in detail, pharmaceutical compositions of the present disclosure may be specially formulated for administration in solid or liquid form, including those adapted for the following: oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, e.g., those targeted for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; topical application, for example, as a cream, ointment, or a controlled-release patch or spray applied to the skin, lungs, or oral cavity; intravaginally or intrarectally, for example, as a pessary, cream or foam; sublingually; ocularly; transdermally; or nasally, pulmonary and to other mucosal surfaces. 
     Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions. 
     Examples of pharmaceutically acceptable antioxidants include: water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. 
     Formulations for use in accordance with the present disclosure include those suitable for oral, nasal, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient, which can be combined with a carrier material, to produce a single dosage form will vary depending upon the host being treated, and the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound, which produces a therapeutic effect. Generally, this amount will range from about 1% to about 99% of active ingredient. In some embodiments, this amount will range from about 5% to about 70%, from about 10% to about 50%, or from about 20% to about 40%. 
     In certain embodiments, a formulation as described herein comprises an excipient selected from the group consisting of cyclodextrins, liposomes, micelle forming agents, e.g., bile acids, and polymeric carriers, e.g., polyesters and polyanhydrides; and a compound of the present disclosure. In certain embodiments, an aforementioned formulation renders orally bioavailable a described compound of the present disclosure. 
     Methods of preparing formulations or compositions comprising described compounds include a step of bringing into association a compound of the present disclosure with the carrier and, optionally, one or more accessory ingredients. In general, formulations may be prepared by uniformly and intimately bringing into association a compound of the present disclosure with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product. 
     The pharmaceutical compositions may be in the form of a sterile injectable preparation, for example, as a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are mannitol, water, Ringer&#39;s solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or diglycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as those described in Pharmacopeia Helvetica, or a similar alcohol. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation. 
     In some cases, in order to prolong the effect of a drug, it may be desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. 
     Injectable depot forms are made by forming microencapsule matrices of the described compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions, which are compatible with body tissue. 
     The pharmaceutical compositions of this disclosure may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, and aqueous suspensions and solutions. In the case of tablets for oral use, carriers, which are commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions and solutions and propylene glycol are administered orally, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and/or flavoring and/or coloring agents may be added. 
     Formulations described herein suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the present disclosure as an active ingredient. Compounds described herein may also be administered as a bolus, electuary or paste. 
     In solid dosage forms for oral administration (capsules, tablets, pills, dragees, powders, granules and the like), an active ingredient is mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; humectants, such as glycerol; disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; solution retarding agents, such as paraffin; absorption accelerators, such as quaternary ammonium compounds; wetting agents, such as, for example, cetyl alcohol, glycerol monostearate, and non-ionic surfactants; absorbents, such as kaolin and bentonite clay; lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and coloring agents. In the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-shelled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. 
     Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface-active or dispersing agent. Molded tablets may be made in a suitable machine in which a mixture of the powdered compound is moistened with an inert liquid diluent. If a solid carrier is used, the preparation can be in tablet form, placed in a hard gelatin capsule in powder or pellet form, or in the form of a troche or lozenge. The amount of solid carrier will vary, e.g., from about 25 to 800 mg, preferably about 25 mg to 400 mg. When a liquid carrier is used, the preparation can be, e.g., in the form of a syrup, emulsion, soft gelatin capsule, sterile injectable liquid such as an ampule or nonaqueous liquid suspension. Where the composition is in the form of a capsule, any routine encapsulation is suitable, for example, using the aforementioned carriers in a hard gelatin capsule shell. 
     Tablets and other solid dosage forms, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may alternatively or additionally be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be formulated for rapid release, e.g., freeze-dried. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. 
     Liquid dosage forms for oral administration of compounds of the disclosure include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. 
     Besides inert diluents, oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents. 
     Suspensions, in addition to active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. 
     The pharmaceutical compositions of this disclosure may also be administered in the form of suppositories for rectal administration. These compositions can be prepared by mixing a compound of this disclosure with a suitable non-irritating excipient, which is solid at room temperature but liquid at the rectal temperature and therefore will melt in the rectum to release the active components. Such materials include, but are not limited to, cocoa butter, beeswax and polyethylene glycols. 
     Topical administration of the pharmaceutical compositions of this disclosure is especially useful when the desired treatment involves areas or organs readily accessible by topical application. For application topically to the skin, the pharmaceutical composition should be formulated with a suitable ointment containing the active components suspended or dissolved in a carrier. Carriers for topical administration of the compounds of this disclosure include, but are not limited to, mineral oil, liquid petroleum, white petroleum, propylene glycol, polyoxyethylene polyoxypropylene compound, emulsifying wax and water. Alternatively, the pharmaceutical composition can be formulated with a suitable lotion or cream containing the active compound suspended or dissolved in a carrier. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. The pharmaceutical compositions of this disclosure may also be topically applied to the lower intestinal tract by rectal suppository formulation or in a suitable enema formulation. Topically-administered transdermal patches are also included in this disclosure. 
     The pharmaceutical compositions of this disclosure may be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art. 
     For ophthalmic use, the pharmaceutical compositions may be formulated as micronized suspensions in isotonic, pH adjusted sterile saline, or, preferably, as solutions in isotonic, pH adjusted sterile saline, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutical compositions may be formulated in an ointment such as petrolatum. 
     Transdermal patches have the added advantage of providing controlled delivery of a compound of the present disclosure to the body. Dissolving or dispersing the compound in the proper medium can make such dosage forms. Absorption enhancers can also be used to increase the flux of the compound across the skin. Either providing a rate controlling membrane or dispersing the compound in a polymer matrix or gel can control the rate of such flux. 
     Examples of suitable aqueous and nonaqueous carriers, which may be employed in the pharmaceutical compositions of the disclosure, include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. 
     Such compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Inclusion of one or more antibacterial and/orantifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like, may be desirable in certain embodiments. It may alternatively or additionally be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents, which delay absorption such as aluminum monostearate and gelatin. 
     In certain embodiments, a described compound or pharmaceutical preparation is administered orally. In other embodiments, a described compound or pharmaceutical preparation is administered intravenously. Alternative routes of administration include sublingual, intramuscular, and transdermal administrations. 
     When compounds described herein are administered as pharmaceuticals, to humans and animals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1% to 99.5% (more preferably, 0.5% to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier. 
     Preparations described herein may be given orally, parenterally, topically, or rectally. They are of course given in forms suitable for the relevant administration route. For example, they are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administrations are preferred. 
     Such compounds may be administered to humans and other animals for therapy by any suitable route of administration, including orally, nasally, as by, for example, a spray, rectally, intravaginally, parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually. 
     Regardless of the route of administration selected, compounds described herein which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present disclosure, are formulated into pharmaceutically-acceptable dosage forms by conventional methods known to those of skill in the art. 
     Actual dosage levels of the active ingredients in the pharmaceutical compositions of the disclosure may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. 
     The terms “administration of” and or “administering” should be understood to mean providing a pharmaceutical composition in a therapeutically effective amount to the subject in need of treatment. Administration routes can be enteral, topical or parenteral. As such, administration routes include but are not limited to intracutaneous, subcutaneous, intravenous, intraperitoneal, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, transdermal, transtracheal, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrasternal, oral, sublingual buccal, rectal, vaginal, nasal ocular administrations, as well infusion, inhalation, and nebulization. 
     The term “cancer” refers to a group diseases characterized by abnormal and uncontrolled cell proliferation starting at one site (primary site) with the potential to invade and to spread to others sites (secondary sites, metastases) which differentiate cancer (malignant tumor) from benign tumor. Virtually all the organs can be affected, leading to more than 100 types of cancer that can affect humans. Cancers can result from many causes including genetic predisposition, viral infection, exposure to ionizing radiation, exposure environmental pollutant, tobacco and or alcohol use, obesity, poor diet, lack of physical activity or any combination thereof. 
     Exemplary cancers described by the national cancer institute include: Acute Lymphoblastic Leukemia, Adult; Acute Lymphoblastic Leukemia, Childhood; Acute Myeloid Leukemia, Adult; Adrenocortical Carcinoma; Adrenocortical Carcinoma, Childhood; AIDS-Related Lymphoma; AIDS-Related Malignancies; Anal Cancer; Astrocytoma, Childhood Cerebellar; Astrocytoma, Childhood Cerebral; Bile Duct Cancer, Extrahepatic; Bladder Cancer; Bladder Cancer, Childhood; Bone Cancer, Osteosarcoma/Malignant Fibrous Histiocytoma; Brain Stem Glioma, Childhood; Brain Tumor, Adult; Brain Tumor, Brain Stem Glioma, Childhood; Brain Tumor, Cerebellar Astrocytoma, Childhood; Brain Tumor, Cerebral Astrocytoma/Malignant Glioma, Childhood; Brain Tumor, Ependymoma, Childhood; Brain Tumor, Medulloblastoma, Childhood; Brain Tumor, Supratentorial Primitive Neuroectodermal Tumors, Childhood; Brain Tumor, Visual Pathway and Hypothalamic Glioma, Childhood; Brain Tumor, Childhood (Other); Breast Cancer; Breast Cancer and Pregnancy; Breast Cancer, Childhood; Breast Cancer, Male; Bronchial Adenomas/Carcinoids, Childhood: Carcinoid Tumor, Childhood; Carcinoid Tumor, Gastrointestinal; Carcinoma, Adrenocortical; Carcinoma, Islet Cell; Carcinoma of Unknown Primary; Central Nervous System Lymphoma, Primary; Cerebellar Astrocytoma, Childhood; Cerebral Astrocytoma/Malignant Glioma, Childhood; Cervical Cancer; Childhood Cancers; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Myeloproliferative Disorders; Clear Cell Sarcoma of Tendon Sheaths; Colon Cancer; Colorectal Cancer, Childhood; Cutaneous T-Cell Lymphoma; Endometrial Cancer; Ependymoma, Childhood; Epithelial Cancer, Ovarian; Esophageal Cancer; Esophageal Cancer, Childhood; Ewing&#39;s Family of Tumors; Extracranial Germ Cell Tumor, Childhood; Extragonadal Germ Cell Tumor; Extrahepatic Bile Duct Cancer; Eye Cancer, Intraocular Melanoma; Eye Cancer, Retinoblastoma; Gallbladder Cancer; Gastric (Stomach) Cancer; Gastric (Stomach) Cancer, Childhood; Gastrointestinal Carcinoid Tumor; Germ Cell Tumor, Extracranial, Childhood; Germ Cell Tumor, Extragonadal; Germ Cell Tumor, Ovarian; Gestational Trophoblastic Tumor; Glioma. Childhood Brain Stem; Glioma. Childhood Visual Pathway and Hypothalamic; Hairy Cell Leukemia; Head and Neck Cancer; Hepatocellular (Liver) Cancer, Adult (Primary); Hepatocellular (Liver) Cancer, Childhood (Primary); Hodgkin&#39;s Lymphoma, Adult; Hodgkin&#39;s Lymphoma, Childhood; Hodgkin&#39;s Lymphoma During Pregnancy; Hypopharyngeal Cancer; Hypothalamic and Visual Pathway Glioma, Childhood; Intraocular Melanoma; Islet Cell Carcinoma (Endocrine Pancreas); Kaposi&#39;s Sarcoma; Kidney Cancer; Laryngeal Cancer; Laryngeal Cancer, Childhood; Leukemia, Acute Lymphoblastic, Adult; Leukemia, Acute Lymphoblastic, Childhood; Leukemia, Acute Myeloid, Adult; Leukemia, Acute Myeloid, Childhood; Leukemia, Chronic Lymphocytic; Leukemia, Chronic Myelogenous; Leukemia, Hairy Cell; Lip and Oral Cavity Cancer; Liver Cancer, Adult (Primary); Liver Cancer, Childhood (Primary); Lung Cancer, Non-Small Cell; Lung Cancer, Small Cell; Lymphoblastic Leukemia, Adult Acute; Lymphoblastic Leukemia, Childhood Acute; Lymphocytic Leukemia, Chronic; Lymphoma, AIDS—Related; Lymphoma, Central Nervous System (Primary); Lymphoma, Cutaneous T-Cell; Lymphoma, Hodgkin&#39;s, Adult; Lymphoma, Hodgkin&#39;s; Childhood; Lymphoma, Hodgkin&#39;s During Pregnancy; Lymphoma, Non-Hodgkin&#39;s, Adult; Lymphoma, Non-Hodgkin&#39;s, Childhood; Lymphoma, Non-Hodgkin&#39;s During Pregnancy; Lymphoma, Primary Central Nervous System; Macroglobulinemia, Waldenstrom&#39;s; Male Breast Cancer; Malignant Mesothelioma, Adult; Malignant Mesothelioma, Childhood; Malignant Thymoma; Medulloblastoma, Childhood; Melanoma; Melanoma, Intraocular; Merkel Cell Carcinoma; Mesothelioma, Malignant; Metastatic Squamous Neck Cancer with Occult Primary; Multiple Endocrine Neoplasia Syndrome, Childhood; Multiple Myeloma/Plasma Cell Neoplasm; Mycosis Fungoides; Myelodysplasia Syndromes; Myelogenous Leukemia, Chronic; Myeloid Leukemia, Childhood Acute; Myeloma, Multiple; Myeloproliferative Disorders, Chronic; Nasal Cavity and Paranasal Sinus Cancer; Nasopharyngeal Cancer; Nasopharyngeal Cancer, Childhood; Neuroblastoma; Non-Hodgkin&#39;s Lymphoma, Adult; Non-Hodgkin&#39;s Lymphoma, Childhood; Non-Hodgkin&#39;s Lymphoma During Pregnancy; Non-Small Cell Lung Cancer; Oral Cancer, Childhood; Oral Cavity and Lip Cancer; Oropharyngeal Cancer; Osteosarcoma/Malignant Fibrous Histiocytoma of Bone; Ovarian Cancer, Childhood; Ovarian Epithelial Cancer; Ovarian Germ Cell Tumor; Ovarian Low Malignant Potential Tumor; Pancreatic Cancer; Pancreatic Cancer, Childhood′, Pancreatic Cancer, Islet Cell; Paranasal Sinus and Nasal Cavity Cancer; Parathyroid Cancer; Penile Cancer; Pheochromocytoma; Pineal and Supratentorial Primitive Neuroectodermal Tumors, Childhood; Pituitary Tumor; Plasma Cell Neoplasm/Multiple Myeloma; Pleuropulmonary Blastoma; Pregnancy and Breast Cancer; Pregnancy and Hodgkin&#39;s Lymphoma; Pregnancy and Non-Hodgkin&#39;s Lymphoma; Primary Central Nervous System Lymphoma; Primary Liver Cancer, Adult; Primary Liver Cancer, Childhood; Prostate Cancer; Rectal Cancer; Renal Cell (Kidney) Cancer; Renal Cell Cancer, Childhood; Renal Pelvis and Ureter, Transitional Cell Cancer; Retinoblastoma; Rhabdomyosarcoma, Childhood; Salivary Gland Cancer; Salivary Gland&#39;Cancer, Childhood; Sarcoma, Ewing&#39;s Family of Tumors; Sarcoma, Kaposi&#39;s; Sarcoma (OsteosarcomaVMalignant Fibrous Histiocytoma of Bone; Sarcoma, Rhabdomyosarcoma, Childhood; Sarcoma, Soft Tissue, Adult; Sarcoma, Soft Tissue, Childhood; Sezary Syndrome; Skin Cancer; Skin Cancer, Childhood; Skin Cancer (Melanoma); Skin Carcinoma, Merkel Cell; Small Cell Lung Cancer; Small Intestine Cancer; Soft Tissue Sarcoma, Adult; Soft Tissue Sarcoma, Childhood; Squamous Neck Cancer with Occult Primary, Metastatic; Stomach (Gastric) Cancer; Stomach (Gastric) Cancer, Childhood; Supratentorial Primitive Neuroectodermal Tumors, Childhood; T-Cell Lymphoma, Cutaneous; Testicular Cancer; Thymoma, Childhood; Thymoma, Malignant; Thyroid Cancer; Thyroid Cancer, Childhood; Transitional Cell Cancer of the Renal Pelvis and Ureter; Trophoblastic Tumor, Gestational; Unknown Primary Site, Cancer of, Childhood; Unusual Cancers of Childhood; Ureter and Renal Pelvis, Transitional Cell Cancer; Urethral Cancer; Uterine Sarcoma; Vaginal Cancer; Visual Pathway and Hypothalamic Glioma, Childhood; Vulvar Cancer; Waldenstrom&#39;s Macro globulinemia; and Wilms&#39; Tumor. 
     In certain aspects, cancer include Lung cancer, Breast cancer, Colorectal cancer, Prostate cancer, Stomach cancer, Liver cancer, cervical cancer, Esophageal cancer, Bladder cancer, Non-Hodgkin lymphoma, Leukemia, Pancreatic cancer, Kidney cancer, endometrial cancer, Head and neck cancer, Lip cancer, oral cancer, Thyroid cancer, Brain cancer, Ovary cancer, Melanoma, Gallbladder cancer, Laryngeal cancer, Multiple myeloma, Nasopharyngeal cancer, Hodgkin lymphoma, Testis cancer and Kaposi sarcoma. 
     In certain aspects, the method further includes administering a chemotherapeutic agent. The compounds of the disclosure can be administered in combination with one or more additional therapeutic agents. The phrases “combination therapy”, “combined with” and the like refer to the use of more than one medication or treatment simultaneously to increase the response. The FGFR inhibitor of the present disclosure might for example be used in combination with other drugs or treatment in use to treat cancer. In various aspect, the compound is administered prior to, simultaneously with or following the administration of the chemotherapeutic agent. 
     The term “anti-cancer therapy” refers to any therapy or treatment that can be used for the treatment of a cancer. Anti-cancer therapies include, but are not limited to, surgery, radiotherapy, chemotherapy, immune therapy and targeted therapies. 
     Examples of chemotherapeutic agents or anti-cancer agents include, but are not limited to, Actinomycin, Azacitidine, Azathioprine, Bleomycin, Bortezomib, Carboplatin, Capecitabine, Cisplatin, Chlorambucil, Cyclophosphamide, Cytarabine, Daunorubicin, Docetaxel, Doxifluridine, Doxorubicin, Epirubicin, Epothilone, Etoposide, Fiuorouracil, Gemcitabine, Hydroxyurea, Idarubicin, Imatinib, lrinotecan, Mechlorethamine, Mercaptopurine, Methotrexate, Mitoxantrone, Oxaliplatin, Paclitaxel, Pemetrexed, Teniposide, Tioguanine, Topotecan, Valrubicin, Vinblastine, Vincristine, Vindesine, Vinorelbine, panitumamab, Erbitux (cetuximab), matuzumab, IMC-IIF 8, TheraCIM hR3, denosumab, Avastin (bevacizumab), Humira (adalimumab), Herceptin (trastuzumab), Remicade (infliximab), rituximab, Synagis (palivizumab), Mylotarg (gemtuzumab oxogamicin), Raptiva (efalizumab), Tysabri (natalizumab), Zenapax (dacliximab), NeutroSpec (Technetium (99mTc) fanolesomab), tocilizumab, ProstaScint (Indium-Ill labeled Capromab Pendetide), Bexxar (tositumomab), Zevalin (ibritumomab tiuxetan (IDEC-Y2B8) conjugated to yttrium 90), Xolair (omalizumab), MabThera (Rituximab), ReoPro (abciximab), MabCampath (alemtuzumab), Simulect (basiliximab), LeukoScan (sulesomab), CEA-Scan (arcitumomab), Verluma (nofetumomab), Panorex (Edrecolomab), alemtuzumab, CDP 870, natalizumab Gilotrif (afatinib), Lynparza (olaparib), Perjeta (pertuzumab), Otdivo (nivolumab), Bosulif (bosutinib), Cabometyx (cabozantinib), Ogivri (trastuzumab-dkst), Sutent (sunitinib malate), Adcetris (brentuximab vedotin), Alecensa (alectinib), Calquence (acalabrutinib), Yescarta (ciloleucel), Verzenio (abemaciclib), Keytruda (pembrolizumab), Aliqopa (copanlisib), Nerlynx (neratinib), Imfinzi (durvalumab), Darzalex (daratumumab), Tecentriq (atezolizumab), and Tarceva (erlotinib). Examples of immunotherapeutic agent include, but are not limited to, interleukins (Il-2, Il-7, Il-12), cytokines (Interferons, G-CSF, imiquimod), chemokines (CCL3, CC126, CXCL7), immunomodulatory imide drugs (thalidomide and its analogues). 
     In a further embodiment, the disclosure provides a method of inhibiting a kinase activity including contacting a cell with a compound of Formula (I), Formula (II), or Formula (III). In one aspect, the kinase is selected from the group consisting of ALK, EGFR, EPH-B3, FAK, FGFR1, FGFR2, FGFR3, FGFR4, KIT, MEK1, MET, PDGFR-ALPHA, PDGFR-BETA, RET, ROS and TYRO 3. In certain aspects, the kinase is FGFR1, FGFR2, FGFR3 and/or FGFR4. In another aspect, the kinase is FGFR4. In various aspects, the cell is a cancer cell. In many aspects, the cancer cell is a breast, lung, bladder, prostate, ovarian, endometrial, rhabdomyosarcoma, liver or gastric cancer cell. 
     Referring to  FIG. 1 , the FGFR4 kinase contains a cysteine (Cys552) located near the ATP-binding site, in the hinge region of the receptor, which is unique within the FGFR family and rare among other kinases. Covalent inhibitors of FGFR4 kinase afford potent and selective inhibition of FGFRs by covalently targeting a thiol group (SH) in the cysteine residue. 
     The screening method employed in the current disclosure according to some embodiments is described as following. Screen probes against live cells or live animals can include the step of (1) treatment of live cells with an electrophilic probe leads to the covalent linkage between target proteins and the probe; (2) lyse cells; (3) add biotin-azide to conjugate biotin to probe-modified proteins via the Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) click reaction; (4) use streptavidin resin to pull down and enrich biotin-conjugated proteins; (5) digest resin-bound proteins with trypsin; (6) analyze resulting tryptic peptides with liquid chromatography-mass spectrometry (LC-MS) or MS; (7) obtain information on identity of target proteins as well as strength of probe-target interaction in cells. The target confirmation and selection can include the steps of (1) use orthogonal methods such as western blots to confirm that the identified proteins indeed bind to the probe; and (2) select the most disease-relevant target-lead pairs for further preclinical and clinical studies. 
     Presented below are examples discussing the design and evaluation of efficacy of new pyridinylpyrimidine-based FGFR inhibitors, contemplated for the discussed applications. The following examples are provided to further illustrate the embodiments of the present disclosure, but are not intended to limit the scope of the disclosure. While they are typical of those that might be used, other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used. 
     EXAMPLES 
     Example 1 
     Synthesis and Characterization of the Pyridinylpyrimidine-Based FGFR Inhibitors (Compounds 1-4) 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 1 was synthesized based on synthetic scheme 1. 
     
       
         
         
             
             
         
       
     
     Compound 2 was synthesized based on synthetic scheme 2. 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 3 was synthesized based on synthetic scheme 3. 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 4 was synthesized based on synthetic scheme 4. 
     Example 2 
     Synthesis of Compound 6 
     (N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(1-methylazetidin-3-yl)oxy-phenyl]prop-2-enamide) 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 6 was synthesized based on synthetic scheme 5. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 6: A solution of 4-amino-3-nitro-phenol (3 g, 19.46 mmol), tert-butyl 3-iodoazetidine-1-carboxylate (6.06 g, 21.41 mmol), Cs 2 CO 3  (9.51 g, 29.20 mmol) in DMF (60 mL) was stirred at 90° C. for 16 hours under N 2  atmosphere. The mixture was diluted with water (5 mL), extratced with EtOAc (10 mL×3), then the combined organic layers were washed with sat. aq. NaCl(5 mL×7), dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (PE/EtOAc=1/0 to 3/1) to afford tert-butyl 3-(4-amino-3-nitro-phenoxy)azetidine-1-carboxylate (5.4 g, 17.46 mmol, 90% yield) as a red solid.  1 H NMR (400 MHz, DMSO-d 6 ): δ=7.28 (d, J=4.0 Hz, 1H), 7.18-7.14 (m, 2H), 7.02 (d, J=9.2 Hz, 1H), 4.97-4.92 (m, 1H), 4.26-4.23 (m, 2H), 3.79-3.76 (m, 2H), 1.38 (s, 9H). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 6: To a solution of N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (800 mg, 1.76 mmol), tert-butyl 3-(4-amino-3-nitro-phenoxy)azetidine-1-carboxylate (652 mg, 2.11 mmol) in DMAc (15 mL) was added t-BuOK (595 mg, 5.31 mmol). The mixture was stirred at 45° C. for 2 hours. The mixture was diluted with water (20 mL), extracted with EtOAc (30 mL×3), then the combined organic layers were washed with sat. aq. NaCl (20 mL×7), dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (PE/EtOAc=1/0 to 3/1) to afford tert-butyl 3-[4-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-3-nitro-phenoxy]azetidine-1-carboxylate (648 mg, 0.947 mmol, 54% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 6: To a solution of tert-butyl 3-[4-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-3-nitro-phenoxy]azetidine-1-carboxylate (648 mg, 0.947 mmol) in dioxane (10 mL) was added HCl/dioxane (4 M, 2.37 mL). The mixture was stirred at 25° C. for 2 hours. The mixture was concentrated to afford N-[4-(azetidin-3-yloxy)-2-nitro-phenyl]-6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-amine (550 mg, 0.886 mmol, 93% yield, HCl salt) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 6: To a solution of N-[4-(azetidin-3-yloxy)-2-nitro-phenyl]-6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-amine (550 mg, 0.886 mmol, HCl salt) in MeOH (15 mL) was added aqueous HCHO (2.88 g, 35.43 mmol, 2.64 mL, 37% purity), NaBH(OAc) 3  (376 mg, 1.77 mmol), CH 3 COOH (213 mg, 3.54 mmol). The mixture was stirred at 25° C. for 4 hours. The mixture was concentrated and the residue was purified by silica gel chromatography (DCM/MeOH=1/0 to 10/1) to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-(1-methylazetidin-3-yl)oxy-2-nitro-phenyl]pyrimidin-4-amine (450 mg, 0.752 mmol, 85% yield) as a red solid. 
     
       
         
         
             
             
         
       
     
     Step 5 to synthesize compound 6: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-(1-methylazetidin-3-yl)oxy-2-nitro-phenyl]pyrimidin-4-amine (450 mg, 0.752 mmol) in THE (15 mL) and H 2 O (15 mL) was added NH 4 C 1  (201 mg, 3.76 mmol), Fe (210 mg, 3.76 mmol). The mixture was stirred at 65° C. for 4 hours. The mixture was filtered and the filtrate was concentrated to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(1-methylazetidin-3-yl)oxy-benzene-1,2-diamine (400 mg, 0.704 mmol, 93% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 6 to synthesize compound 6: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(1-methylazetidin-3-yl)oxy-benzene-1,2-diamine (200 mg, 0.352 mmol) in DCM (10 mL) was added Et 3 N (36 mg, 0.352 mmol) and prop-2-enoyl chloride (32 mg, 0.352 mmol). The mixture was stirred at 25° C. for 0.5 hour. The mixture was diluted with water (10 mL), extracted with DCM (10 mL×3), then the combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by preparative HPLC (water(0.225% FA)-ACN) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(1-methylazetidin-3-yl)oxy-phenyl]prop-2-enamide (8.5 mg, 4% yield, 96% purity) as a white solid. LCMS: t R =2.928 min in 0-60CD_4 min_Pos_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=622.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=10.93 (s, 1H), 9.68 (s, 1H), 9.02 (s, 1H), 8.61 (s, 1H), 8.39 (s, 1H), 8.06-7.95 (m, 2H), 7.41-7.31 (m, 2H), 6.86-6.83 (m, 2H), 6.69-6.66 (m, 2H), 6.25 (d, J=2.0 Hz, 1H), 5.73-5.70 (m, 1H), 4.76-4.70 (m, 1H), 3.93 (s, 6H), 3.76-3.72 (m, 2H), 3.01-2.98 (m, 2H), 2.30 (s, 3H). 
     Example 3 
     Synthesis of Compound 7 
     N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-[(1-methylazetidin-3-yl)methoxy]phenyl]prop-2-enamide 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 7 was synthesized based on synthetic scheme 6. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 7: To a solution of tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (2 g, 10.68 mmol) in DCM (5 mL) was added DABCO (2.40 g, 21.36 mmol) and TsCl(2.44 g, 12.82 mmol). The mixture was stirred at 0° C. for 0.5 hr. The mixture was filtered and the filtrate was diluted with H 2 O (50 mL) and extracted with DCM (50 mL×3). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to afford tert-butyl 3-(p-tolylsulfonyloxymethyl)azetidine-1-carboxylate (3 g, 8.79 mmol, 82% yield) as a colorless oil, which was used directly in the next step. 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 7: To a solution of tert-butyl 3-(p-tolylsulfonyloxymethyl)azetidine-1-carboxylate (2 g, 5.86 mmol) in DMF (20 mL) was added Cs 2 CO 3  (3.82 g, 11.72 mmol) and 4-amino-3-nitro-phenol (1.35 g, 8.79 mmol). The mixture was stirred at 80° C. for 12 hr. The mixture was quenched by addition of H 2 O (50 mL) at 25° C., and then diluted with H 2 O (50 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. After that the residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜50% Ethyl acetate/Petroleum ether gradient @ 40 mL/min) to afford tert-butyl 3-[(4-amino-3-nitro-phenoxy)methyl]azetidine-1-carboxylate (1.4 g, 4.33 mmol, 74% yield) as a brown solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 7: To a solution of tert-butyl 3-[(4-amino-3-nitro-phenoxy)methyl]azetidine-1-carboxylate (1.4 g, 4.33 mmol) in DMF (5 mL) was added t-BuOK (583 mg, 5.20 mmol) and N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (1.97 g, 4.33 mmol). The mixture was stirred at 40° C. for 2 hr. The mixture was quenched by addition of H 2 O (50 mL) at 25° C., and then diluted with H 2 O (50 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. After that the residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜ 70 % Ethyl acetate/Petroleum ether gradient @ 40 mL/min) to afford tert-butyl 3-[[4-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-3-nitro-phenoxy]methyl]azetidine-1-carboxylate (1 g, 1.29 mmol, 30% yield, 90% purity) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 7: A solution of tert-butyl 3-[[4-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-3-nitro-phenoxy]methyl]azetidine-1-carboxylate (0.95 g, 1.36 mmol) in HCl/dioxane (4 M, 10 mL) was stirred at 25° C. for 0.5 hr. The mixture was concentrated under reduced pressure to afford N-[4-(azetidin-3-ylmethoxy)-2-nitro-phenyl]-6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-amine (1.17 g, 1.35 mmol, 99% yield, 69% purity) as a yellow solid, which was used directly in the next step. 
     
       
         
         
             
             
         
       
     
     Step 5 to synthesize compound 7: To a solution of N-[4-(azetidin-3-ylmethoxy)-2-nitro-phenyl]-6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-amine (1 g, 1.22 mmol) in MeOH (10 mL) was added aqueous HCHO (3.96 g, 48.79 mmol, 3.63 mL, 37% purity), CH 3 COOH (293 mg, 4.88 mmol) and NaBH(OAc) 3  (517 mg, 2.44 mmol). The mixture was stirred at 25° C. for 4 hr. The mixture was concentrated under reduced pressure to give a residue. After that the residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜80% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-[(1-methylazetidin-3-yl)methoxy]-2-nitro-phenyl]pyrimidin-4-amine (0.5 g, 0.735 mmol, 60% yield, 90% purity) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 6 to synthesize compound 7: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-[(1-methylazetidin-3-yl)methoxy]-2-nitro-phenyl]pyrimidin-4-amine (0.5 g, 0.816 mmol) in THE (1 mL) and H 2 O (1 mL) was added Fe (228 mg, 4.08 mmol) and NH 4 C 1  (218 mg, 4.08 mmol). The mixture was stirred at 60° C. for 5 hr. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. After that the mixture was quenched by addition of H 2 O (50 mL) at 25° C., and then diluted with H 2 O (50 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-[(1-methylazetidin-3-yl)methoxy]benzene-1,2-diamine (350 mg, 0.60 mmol, 74% yield) as a brown solid. 
     
       
         
         
             
             
         
       
     
     Step 7 to synthesize compound 7: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-[(1-methylazetidin-3-yl)methoxy]benzene-1,2-diamine (0.2 g, 0.343 mmol) in DCM (5 mL) was added DIEA (133 mg, 1.03 mmol) and prop-2-enoyl chloride (34 mg, 0.378 mmol). The mixture was stirred at 0° C. for 0.5 hr. The mixture was quenched by addition of H 2 O (50 mL) at 25° C., and then diluted with H 2 O (50 mL) and extracted with DCM (50 mL×3). The combined organic layers were washed with brine (50 mL), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. After that the residue was purified by preparative HPLC (water(0.225% FA)-ACN) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-[(1-methylazetidin-3-yl)methoxy]phenyl]prop-2-enamide (4.8 mg, 2% yield, 92.8% purity) as a white solid. LCMS: t R =1.425 min in 10-80AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=636.3 [M+H] + .  1 H NMR (400 MHz, Methanol): δ=8.62 (s, 1H), 8.50 (s, 1H), 8.00-7.98 (m, 2H), 7.58-7.44 (m, 2H), 7.02-6.78 (m, 4H), 6.45-6.33 (m, 2H), 5.76 (d, J=9.6 Hz, 1H), 4.35-4.14 (m, 6H), 3.96 (s, 6H), 3.24, 2.98 (s, 3H), 2.61-2.57 (m, 1H). 
     Example 4 
     Synthesis of Compound 8 
     N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-[(1-methyl-4-piperidyl)oxy]phenyl]prop-2-enamide 
     
       
         
         
             
             
         
       
     
     Compound 8 was synthesized based on synthetic scheme 7. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 8: To a solution of 1-methylpiperidin-4-ol (1.3 g, 11.29 mmol) in THF (10 mL) was added KOH (2.53 g, 45.15 mmol) and TsCl(3.23 g, 16.93 mmol) at 0° C. The mixture was stirred at 25° C. for 16 hr. The mixture was poured into water (30 ml) and filtered; the filter cake was collected, dried to afford (1-methyl-4-piperidyl) 4-methylbenzenesulfonate (1.8 g, 6.68 mmol, 59% yield) as a yellow oil. 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 8: To a solution of 4-amino-3-nitro-phenol (400 mg, 2.60 mmol) and (1-methyl-4-piperidyl) 4-methylbenzenesulfonate (1.05 g, 3.89 mmol) in DMF (20 mL) was added Cs 2 CO 3  (1.69 g, 5.19 mmol). The mixture was stirred at 80° C. for 8 hr. The residue was diluted with EtOAc (20 mL) and extracted with H 2 O (60 mL). The combined organic layers were washed with H 2 O (30 mL×2), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0-10% methanol/dichloromethane @ 40 mL/min) to afford 5-[(1-methyl-4-piperidyl)oxy]-2-nitro-aniline (230 mg, 0.915 mmol, 35% yield) as a brown solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 8: To a solution of 4-[(1-methyl-4-piperidyl)oxy]-2-nitro-aniline (138 mg, 0.549 mmol) and N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (300 mg, 0.659 mmol) in DMAc (10 mL) was added tBuOK (123 mg, 1.10 mmol). The mixture was stirred at 50° C. for 2 hr. The residue was diluted with H 2 O (20 mL) and extracted with EtOAc (20 mL×3). The combined organic layers were washed with H 2 O (30 mL×2), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜10% methanol/dichloromethane @ 40 mL/min) to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-[(1-methyl-4-piperidyl)oxy]-2-nitro-phenyl]pyrimidin-4-amine (200 mg, 0.16 mmol, 29% yield) as a brown solid. 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 8: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-[(1-methyl-4-piperidyl)oxy]-2-nitro-phenyl]pyrimidin-4-amine (200 mg, 0.16 mmol) in THF (10 mL) and H 2 O (10 mL) was added NH 4 C 1  (43 mg, 0.8 mmol) and Fe (45 mg, 0.8 mmol). The mixture was stirred at 65° C. for 3 hr. The mixture was filtered with diatomite, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜10% Methanol/Dichloromethane @ 40 mL/min) to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-[(1-methyl-4-piperidyl)oxy]benzene-1,2-diamine (38 mg, 0.064 mmol, 40% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 5 to synthesize compound 8: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-[(1-methyl-4-piperidyl)oxy]benzene-1,2-diamine (38 mg, 0.064 mmmol) in DCM (10 mL) and DIEA (16 mg, 0.127 mmol) was added prop-2-enoyl chloride (7 mg, 0.076 mmol). The mixture was stirred at 0° C. for 0.5 hr. The mixture was concentrated under reduced pressure to give the residue. The residue was purified by preparative HPLC (water(0.225% FA)-ACN) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-[(1-methyl-4-piperidyl)oxy]phenyl]prop-2-enamide (11.1 mg, 0.017 mmol, 27% yield, 99.30% purity) as a yellow solid. 
     Example 5 
     Synthesis of Compound 9 
     N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(1-methylpyrrolidin-3-yl)oxy-phenyl]prop-2-enamide 
     
       
         
         
             
             
         
       
     
     Compound 9 was synthesized based on synthetic scheme 8. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 9: To a solution of 1-methylpyrrolidin-3-ol (1.0 g, 9.89 mmol) and KOH (2.22 g, 39.55 mmol) in THE (30 mL) was added TsCl(2.83 g, 14.83 mmol) at 0° C. The mixture was stirred at 25° C. for 16 hours. The mixture was filtered and the filtrate was concentrated to afford (1-methylpyrrolidin-3-yl) 4-methylbenzenesulfonate (1.1 g, 4.31 mmol, 44% yield) as yellow oil. 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 9: To a solution of 4-amino-3-nitro-phenol (600 mg, 3.89 mmol) in DMF (20 mL) was added Cs 2 CO 3  (2.54 g, 7.79 mmol). The mixture was stirred at 25° C. for 0.5 hour, then (1-methylpyrrolidin-3-yl) 4-methylbenzenesulfonate (1.09 g, 4.28 mmol) was added thereto. The mixture was stirred at 80° C. for 6 hours. The mixture was diluted with water (20 mL), extracted with EtOAc (50 mL×3), then the combined organic layers were washed with sat. aq. NaCl (20 mL×7), dried over Na 2 SO 4 , filtered and concentrated. The residue was purified y silica gel chromatography (DCM/MeOH=1/0 to 10/1) to afford 4-(1-methylpyrrolidin-3-yl)oxy-2-nitro-aniline (600 mg, 2.53 mmol, 65% yield) as a red solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 9: To a solution of 4-(1-methylpyrrolidin-3-yl)oxy-2-nitro-aniline (200 mg, 0.843 mmol), N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (422 mg, 0.927 mmol) in DMAC (10 mL) was added t-BuOK (286 mg, 2.55 mmol). The mixture was stirred at 40° C. for 2 hours. The mixture was diluted with water (20 mL), extracted with EtOAc (50 mL×3), then the combined organic layers were dried over Na 2 SO 4 , filtered and concentrated to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-(1-methylpyrrolidin-3-yl)oxy-2-nitro-phenyl]pyrimidin-4-amine (500 mg, crude) as yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 9: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[4-(1-methylpyrrolidin-3-yl)oxy-2-nitro-phenyl]pyrimidin-4-amine (300 mg, 0.49 mmol) in THF (10 mL) and H 2 O (10 mL) was added Fe (137 mg, 2.45 mmol) and NH 4 C 1  (131 mg, 2.45 mmol). The mixture was stirred at 65° C. for 4 hours. The mixture was filtered and the filtrate was extracted with EtOAc (30 mL×3), then the combined organic layers were dried over Na 2 SO 4 , filtered and concentrated to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(1-methylpyrrolidin-3-yl)oxy-benzene-1,2-diamine (150 mg, 0.258 mmol, 52% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 5 to synthesize compound 9: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(1-methylpyrrolidin-3-yl)oxy-benzene-1,2-diamine (120 mg, 0.206 mmol) in DCM (10 mL) was added prop-2-enoyl chloride (19 mg, 0.206 mmol) and DIEA (27 mg, 0.206 mmol). The mixture was stirred at 25° C. for 1 hour. The mixture was diluted with water (5 mL), extracted with DCM (10 mL×3), then the combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by preparative HPLC (water(0.225% FA)-ACN) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(1-methylpyrrolidin-3-yl)oxy-phenyl]prop-2-enamide (50 mg, 0.0778 mmol, 38% yield, 99% purity) as yellow solid. LCMS: t R =1.129 min in 10-80AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=636.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=10.88 (s, 1H), 10.15 (s, 1H), 9.65 (s, 1H), 9.10 (s, 1H), 8.64 (s, 1H), 8.06 (d, J=4.4 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.54 (s, 1H), 7.46 (d, J=8.4 Hz, 1H), 7.01-6.98 (m, 1H), 6.88-6.83 (m, 3H), 6.52-6.49 (m, 1H), 6.26-6.21 (m, 1H), 5.74-5.71 (m, 1H), 5.17-5.12 (m, 1H), 3.93 (s, 6H), 3.81-3.61 (m, 1H), 3.41-2.89 (m, 6H), 2.61-2.54 (m, 1H), 2.30-2.10 (m, 1H). 
     Example 6 
     Synthesis of Compound 10 
     N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-tetrahydrofuran-3-yloxy-phenyl]prop-2-enamide 
     
       
         
         
             
             
         
       
     
     Compound 10 was synthesized based on synthetic scheme 9. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 10: To a solution of 4-amino-3-nitro-phenol (4 g, 25.95 mmol), tetrahydrofuran-3-ol (2.29 g, 25.95 mmol) and PPh 3  (8.17 g, 31.14 mmol) in THE (25 mL) was added a solution of DTBAD (8.96 g, 38.93 mmol) in THE (25 mL) dropwise at 0° C. under N 2 . The mixture was stirred at 0° C. for 0.5 h then warmed to 25° C. for 15.5 h. The mixture was concentrated. The residue was purified by column chromatography (SiO 2 , Petroleum ether/Ethyl acetate=5/1 to 3/1) and the residue was recrystalized from CH 3 CN to afford 2-nitro-4-tetrahydrofuran-3-yloxy-aniline (1.1 g, 4.78 mmol, 18% yield, 97.5% purity) as a red solid. LCMS: t R =0.824 min in 0-30AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=225.2 [M+H] + .  1 H NMR (400 MHz, CDCl 3 ): δ=7.44 (s, 1H), 7.00-6.95 (m, 1H), 6.72-6.66 (m, 1H), 5.84 (s, 2H), 4.84-4.80 (m, 1H), 3.93-3.83 (m, 4H), 2.19-2.03 (m, 2H). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 10: To a solution of N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (300 mg, 0.66 mmol) and 2-nitro-4-tetrahydrofuran-3-yloxy-aniline (296 mg, 1.32 mmol) in DMAc (30 mL) was added tBuOK (148 mg, 1.32 mmol). The mixture was stirred at 40° C. for 2 hr. The mixture was poured into water (60 mL) and filtered, the filter cake was collected in vacuo to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-(2-nitro-4-tetrahydrofuran-3-yloxy-phenyl)pyrimidin-4-amine (240 mg, 0.40 mmol, 61% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 10: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-(2-nitro-4-tetrahydrofuran-3-yloxy-phenyl)pyrimidin-4-amine (240 mg, 0.40 mmol) in THF (10 mL) and H 2 O (10 mL) was added Fe (112 mg, 2.00 mmol) and NH 4 C 1  (107 mg, 2.00 mmol). The mixture was stirred at 65° C. for 3 hr. The mixture was filtered with diatomite, and the filtrate was concentrated under reduced pressure to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-tetrahydrofuran-3-yloxy-benzene-1,2-diamine (300 mg, 0.368 mmol, 92% yield, 90% purity) as a red solid. LCMS: t R =0.922 min in 0-60AB_2 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=569.1 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 10: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-tetrahydrofuran-3-yloxy-benzene-1,2-diamine (220 mg, 0.386 mmol) in DCM (10 mL) and DIEA (100 mg, 0.772 mmol) and prop-2-enoyl chloride (31 mg, 0.348 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 hr. The mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (water(0.225% FA)-ACN) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-tetrahydrofuran-3-yloxy-phenyl]prop-2-enamide (100 mg, 0.159 mmol, 41% yield, 99.2% purity) as a yellow solid. LCMS: t R =2.148 min in 0-60AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=623.1 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=9.66 (s, 1H), 8.67 (s, 1H), 8.07-7.93 (m, 2H), 7.44-7.39 (m, 2H), 6.92 (s, 1H), 6.88-6.77 (m, 3H), 6.53-6.49 (m, 1H), 6.26-6.21 (m, 1H), 5.71 (dd, J=10.0 and 2.0 Hz, 1H), 5.00 (t, J=5.6 Hz, 1H), 3.94 (s, 6H), 3.89-3.76 (m, 4H), 2.26-2.21 (m, 1H), 2.04-1.98 (m, 1H). 
     Example 7 
     Synthesis of Compound 11 
     N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(oxetan-3-yloxy)phenyl]prop-2-enamide 
     
       
         
         
             
             
         
       
     
     Compound 11 was synthesized based on synthetic scheme 10. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 11: To a solution of 4-amino-3-nitro-phenol (200 mg, 1.30 mmol) in DMF (5 mL) was added Cs 2 CO 3  (846 mg, 2.60 mmol). The mixture was stirred at 25° C. for 0.5 hour, then oxetan-3-yl 4-methylbenzenesulfonate (444 mg, 1.95 mmol) was added. The mixture was heated to 80° C. for 6 hours. The mixture was diluted with water (10 mL), extracted with EtOAc (20 mL×3), then the combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (PE/EtOAc=1/0 to 3/1) to afford 2-nitro-4-(oxetan-3-yloxy)aniline (100 mg, 0.476 mmol, 37% yield) as red solid.  1 H NMR (400 MHz, DMSO-d 6 ): δ=7.30 (s, 2H), 7.16-7.09 (m, 2H), 7.20 (d, J=9.2 Hz, 1H), 5.27-5.22 (m, 1H), 4.91-4.87 (m, 2H), 4.54-4.51 (m, 2H). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 11: To a solution of N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (300 mg, 0.659 mmol), 2-nitro-4-(oxetan-3-yloxy)aniline (138 mg, 0.659 mmol) in DMAc (10 mL) was added t-BuOK (223 mg, 1.99 mmol) at 0° C. The mixture was then heated to 40° C. a for 2 hours. The mixture was diluted with water (10 mL), extracted with EtOAc (20 mL×3). Then the combined organic layers were washed with sat. aq. NaCl (10 mL×7), dried over Na 2 SO 4 , filtered and concentrated. The residue was triturated with CH 3 CN (5 mL) at 25° C. for 5 min. The precipitation was filtered, dried to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[2-nitro-4-(oxetan-3-yloxy)phenyl]pyrimidin-4-amine (300 mg, 0.512 mmol, 78% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 11: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[2-nitro-4-(oxetan-3-yloxy)phenyl]pyrimidin-4-amine (200 mg, 0.34 mmol) in THE (10 mL) and H 2 O (10 mL) was added Fe (95 mg, 1.71 mmol) and NH 4 C 1  (91 mg, 1.71 mmol). The mixture was stirred at 65° C. for 4 hours. The mixture was cooled to room temperature, filtered, and the filtrated was concentrated to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(oxetan-3-yloxy)benzene-1,2-diamine (180 mg, crude) as yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 11: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(oxetan-3-yloxy)benzene-1,2-diamine (150 mg, 0.27 mmol) in DCM (15 mL) was added prop-2-enoyl chloride (19 mg, 0.216 mmol) at 0° C. The mixture was stirred at 25° C. for 0.5 hour. The mixture was quenched by water (10 mL), then extracted with DCM (50 mL×3), dried over Na 2 SO 4 , filtered and concentrated. The residue was purified preparative HPLC (Colum: Xtimate C18 100*30 mm*3 um, water (0.04% NH 3 .H 2 O+10 mM NH 4 HCO 3 )-ACN; B % from 63 to 83; Gradient Time: 30 min; Flow rate: 25 mL/min) then further purified by chiral SFC (Instrument: CAS-QD-ANA-SFC-SD(Agilent 1260 with DAD detector), Column: Chiralcel OJ-3 100×4.6 mm I.D., 3 um. Mobile phase: A: CO 2  B: ethanol (0.05% DEA), Gradient: from 5% to 40% of B in 4.5 min and hold 40% for 2.5 min, then 5% of B for 1 min Flow rate: 2.8 mL/min, Column temperature: 40° C.) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(oxetan-3-yloxy)phenyl]prop-2-enamide (30 mg, 0.049 mmol, 18% yield, 100% purity) as yellow solid. LCMS: t R =2.023 min in:10-80CD_4 min_Pos_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=609.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=10.93 (s, 1H), 9.66 (s, 1H), 8.98 (s, 1H), 8.61 (s, 1H), 8.07-7.96 (m, 2H), 7.42-7.34 (m, 2H), 6.92 (s, 1H), 6.86-6.84 (m, 2H), 6.66-6.55 (m, 2H), 6.26-6.21 (m, 1H), 5.74-5.71 (m, 1H), 5.29-5.26 (m, 1H), 4.94-4.91 (m, 2H), 4.59-4.56 (m, 2H), 3.37 (s, 6H). 
     Example 8 
     Synthesis of Compound 12 
     N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(2-pyrrolidin-1-ylethoxy)phenyl]prop-2-enamide 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 12 was synthesized based on synthetic scheme 11. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 12: 4-amino-3-nitro-phenol (1.5 g, 9.73 mmol), Boc 2 O (3.19 g, 14.60 mmol) and Et 3 N (984 mg, 9.73 mmol) dissolved in DCM (10 mL). Then a solution of DMAP (118 mg, 0.973 mmol) in DCM (10 mL) was slowly added dropwise to the above solution. Then the mixture was stirred at 25° C. for 2 hours. The mixture was concentrated under reduced pressure to remove DCM. The residue was purified by silica gel chromatography. (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0-30% Ethyl acetate/Petroleum ether gradient @ 40 mL/min) to afford tert-butyl N-(4-hydroxy-2-nitro-phenyl)carbamate (2.35 g, 95% yield) as a yellow solid. LCMS: t R =1.169 min in 10-80AB_2 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=255.1 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 12: A solution of 1-(2-chloroethyl)pyrrolidine (2.25 g, 13.22 mmol, HCl salt), tert-butyl N-(4-hydroxy-2-nitro-phenyl)carbamate (2.8 g, 11.01 mmol), Cs 2 CO 3  (7.18 g, 22.03 mmol,) in DMF (100 mL) was stirred at 50° C. for 8 hours. The mixture was extracted with EtOAc (200 mL×5). The combined organic layers were washed with H 2 O (50 mL×6), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0-35% Ethyl acetate/Petroleum ether gradient @ 40 mL/min) to afford tert-butyl N-[2-nitro-4-(2-pyrrolidin-1-ylethoxy)phenyl]carbamate (1.2 g, 31% yield) as a black solid. LCMS: t R =0.980 min in 10-80 AB_2 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=352.1 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 12: A mixture of tert-butyl N-[2-nitro-4-(2-pyrrolidin-1-ylethoxy)phenyl]carbamate (1.2 g, 3.41 mmol), HCl/dioxane (4 M, 0.85 mL) in MeOH (20 mL) was stirred at 25° C. for 1 hr. The mixture was adjusted to pH=8 by addition of sat. aq. NaHCO 3  and the resulting mixture was concentrated to afford 2-nitro-4-(2-pyrrolidin-1-ylethoxy)aniline (1.0 g, crude) as a yellow solid. LCMS: t R =0.882 min in 0-60 AB_2 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=252.1 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 12: To a solution of N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (352 mg, 0.659 mmol), 2-nitro-4-(2-pyrrolidin-1-ylethoxy)aniline (500 mg, 1.99 mmol) in DMF (30 mL) was added t-BuOK (223 mg, 1.99 mmol) at 0° C. Then the mixture was stirred at 40° C. for 2 hours under N 2  atmosphere. The mixture was extracted with EtOAc (150 mL×5). The combined organic layers were washed with H 2 O (30 mL×6), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0-15% MeOH/DCM gradient @ 20 mL/min) to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[2-nitro-4-(2-pyrrolidin-1-ylethoxy)phenyl]pyrimidin-4-amine (539 mg, 69% yield, 53% purity) as a yellow solid. LCMS: t R =1.004 min in 10-80 AB_2 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=626.1 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 5 to synthesize compound 12: A mixture of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-[2-nitro-4-(2-pyrrolidin-1-ylethoxy)phenyl]pyrimidin-4-amine (400 mg, 0.638 mmol,) and Pd/C (500 mg, 10% purity) in MeOH (30 mL) was stirred at 25° C. for 2 hours under H 2  atmosphere. The mixture was filtered and concentrated under reduced pressure to give a residue. The mixture was concentrated to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(2-pyrrolidin-1-ylethoxy)benzene-1,2-diamine (200 mg, crude) as a black solid. LCMS: t R =1.218 min in 10-80 AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=596.3 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 6 to synthesize compound 12: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-4-(2-pyrrolidin-1-ylethoxy)benzene-1,2-diamine (150 mg, 0.251 mmol) in DCM (4 mL) and Et 3 N (28 mg, 0.277 mmol) was added a solution of prop-2-enoyl chloride (25 mg, 0.277 mmol) in DCM (3 mL) dropwise at 0° C. The mixture was stirred at 25° C. for 0.5 hour. The mixture was concentrated under reduced pressure to remove DCM. The residue was purified by preparative HPLC (Colum: Xtimate C18 100*30 mm*3 um water (0.04% NH 3 .H 2 O+10 mM NH 4 HCO 3 )-ACN; B % from 63 to 83; Gradient Time: 30 min; Flow rate: 25 mL/min) to afford N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-5-(2-pyrrolidin-1-ylethoxy)phenyl]prop-2-enamide (9.1 mg, 5% yield, 98% purity) as a white solid. LCMS: t R =1.550 min in 10-80CD_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=650.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=10.95 (s, 1H), 9.64 (s, 1H), 8.94 (s, 1H), 8.61 (s, 1H), 8.05-7.95 (m, 2H), 7.45-7.38 (m, 2H), 6.94-6.81 (m, 4H), 6.55-6.48 (m, 1H), 6.25-6.21 (m, 1H), 5.72 (d, J=11.2 Hz, 1H), 4.07 (t, J=5.6 Hz, 2H), 3.92 (s, 6H), 2.89-2.73 (m, 6H), 1.69 (s, 4H). 
     Example 9 
     Synthesis of Compound 13 
     N-[5-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-1-methyl-imidazol-4-yl]prop-2-enamide 
     
       
         
         
             
             
         
       
     
     Compound 13 was synthesized based on synthetic scheme 12. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 13: A mixture of 5-chloro-1-methyl-4-nitro-imidazole (2 g, 12.38 mmol) in NH 3 /MeOH (10 mL, 7 M) was stirred at 100° C. for 16 hr in an autoclave. The mixture was cooled down to room temperature, and the precipitation was filtered, washed with MeOH (10 mL×2), dried to afford 3-methyl-5-nitro-imidazol-4-amine (1.6 g, 11.26 mmol, 91% yield) as a yellow solid.  1 H NMR (400 MHz, DMSO-d 6 ): δ=7.55 (s, 2H), 7.25 (s, 1H), 3.47 (s, 3H). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 13: To a solution of N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (500 mg, 1.10 mmol) and 3-methyl-5-nitro-imidazol-4-amine (312 mg, 2.20 mmol) in DMF (20 mL) was added tBuOK (246 mg, 2.20 mmol). The mixture was stirred at 40° C. for 12 hr under N 2  atmosphere. The mixture was diluted with H 2 O (20 mL) and extracted with EtOAc (10 mL×2). The combined organic layers were washed with H 2 O (10 mL×3), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜10% Ethyl acetate/Petroleum ether gradient @ 50 mL/min) to afford 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-(3-methyl-5-nitro-imidazol-4-yl)pyrimidin-4-amine (320 mg, 0.619 mmol, 56% yield) as a yellow solid. 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 13: To a solution of 6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]-N-(3-methyl-5-nitro-imidazol-4-yl)pyrimidin-4-amine (300 mg, 0.58 mmol) in MeOH (5 mL) was added Pd/C (5 mg, 10% purity) under N 2  atmosphere. The suspension was degassed and purged with H 2  for 3 times. The mixture was stirred under H 2  (15 psi) at 25° C. for 2 hr. The liquid was filtered with diatomite, and the filtrate was concentrated under reduced pressure to afford N 5 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-1-methyl-imidazole-4,5-diamine (200 mg, 0.41 mmol, 71% yield) as a brown solid. 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 13: To a solution of N 5 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]-1-methyl-imidazole-4,5-diamine (100 mg, 0.205 mmol) in DCM (10 mL) and DIEA (53 mg, 0.41 mmol) was added prop-2-enoyl chloride (15 mg, 0.164 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 hr. The mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (Column: Phenomenex Luna C18 100*40 mm*3 um; water (0.225% FA) -ACN; B % from 20 to 40; Gradient time: 9 min; Flow rate: 25 mL/min) to afford N-[5-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]-1-methyl-imidazol-4-yl]prop-2-enamide (13.6 mg, 0.024 mmol, 12% yield, 95.34% purity) as a yellow solid. LCMS: t R =0.968 min in 10-80AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=541.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=10.99 (s, 1H), 10.45 (s, 1H), 9.26 (s, 1H), 8.72 (s, 1H), 8.13-8.09 (m, 2H), 7.21-6.86 (m, 3H), 6.43-6.23 (m, 2H), 5.79-5.76 (m, 1H), 4.04 (s, 6H), 3.55 (s, 3H). 
     Example 10 
     Synthesis of Compound 14 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 14 was synthesized based on synthetic scheme 13. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 14: To the mixture of compound 14-2 (30.0 g, 194.8 mmol, 1.0 eq) in ethyl acetate (600 mL) was added compound 14-1 (19 g, 214 mmol, 1.1 eq) and triphenylphosphine (56.0 g, 214.1 mmol, 1.1 eq). Then diethyl azodicarboxylate (33.5 mL, 214.1 mmol, 1.1 eq) was added dropwise. The mixture was stirred at room temperature overnight. The reaction was monitored by TLC. Then the mixture was filtered through a pad of Celite and sintered funnel. The result mixture was extracted with ethyl acetate (3×600 mL) and added 1N HCl and water. The aqueous phase was extracted with ethyl acetate and ammonium hydroxide. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 100:1-50:1-30:1) to give compound 14-3 (4.6 g, 11%). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 14: To the mixture of compound 14-3 (10.0 g, 44.4 mmol, 1.1 eq) and compound 14-4 (18.4 g, 40.4 mmol, 1.0 eq) in dimethylformamide (60 mL) was added potassium tert-butoxide (13.6 g, 121.2 mmol, 3.0 eq) under nitrogen atmosphere. Then the mixture was stirred at 40° C. for 2 h. TLC analysis of the reaction mixture showed partial conversion to the desired product. The mixture was cooled to room temperature and extracted with ethyl acetate and water. The combined organics were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 100:1-50:1) to afford compound 14-5 (5 g, 21%). 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 14: To the mixture of compound 14-5 (5.0 g, 8.3 mmol, 1.0 eq) in ethanol/water (100 mL/20 mL) was added Fe (2.33 g, 41.7 mmol, 5.0 eq) and ammonium chloride (4.46 g, 83.4 mmol, 10.0 eq). Then the mixture was stirred at 85° C. for 2 h. TLC analysis of the reaction mixture showed partial conversion to the desired product. The mixture was filtered and extracted with ethyl acetate (120 mL×3). The combined organics were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 10:1) to afford compound 14-6 (4 g, 85%). 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 14: To the mixture of compound 14-6 (4.0 g, 7.03 mmol, 1.0 eq) in dichloromethane (40 mL) was added compound 14-7 (632.6 mg, 7.03 mmol, 1.0 eq) at 0° C. The mixture was stirred at room temperature for 2 h. TLC analysis of the reaction mixture showed full conversion to the desired product. Then the mixture was quenched with water (200 mL) and extracted with dichloromethane (40 mL×2). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 10:1) to afford the crude product (purity: 90%). The crude product was dissolved in dichloromethane (50 mL). Then the mixture was added 20% sodium hydroxide solution (10 mL). The mixture was stirred at room temperature for 30 min. Then the mixture was extracted with dichloromethane and washed with brine. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give compound 14 (2.0 g, 46%) as yellow solid. LCMS: [M+1] +   624 .  1 H NMR (400 MHz, DMSO): δ 10.94 (s, 1H), 8.58 (s, 1H), 8.02-8.01 (m, 1H), 7.92 (m, 1H), 7.43 (m, 1H), 7.39-7.37 (m, 1H), 6.96 (m, 1H), 6.80-6.78 (m, 3H), 6.76 (m, 1H), 6.46 (m, 1H), 6.17 (m, 1H), 5.73 (s, 1H), 5.69-5.66 (m, 1H), 4.03-4.00 (m, 3H), 3.90 (s, 8H), 2.61-2.59 (m, 3H) and 2.19 (s, 8H). 
     Example 11 
     Synthesis of Compound 15 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 15 was synthesized based on synthetic scheme 14. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 15: To the mixture of compound 15-2 (30.0 g, 194.6 mmol, 1.0 eq) in ethyl acetate (600 mL) was added compound 15-1 (25.1 g, 214 mmol, 1.1 eq) and triphenylphosphine (56.0 g, 214.1 mmol, 1.1 eq). Then diethyl azodicarboxylate (33.5 mL, 214.1 mmol, 1.1 eq) was added dropwise. The mixture was stirred at room temperature overnight. The reaction was monitored by TLC. Then the mixture was filtered through a pad of celite and sintered funnel. The result mixture was extracted with ethyl acetate (3×600 mL) and added 1N HCl and water. The aqueous phase was extracted with ethyl acetate and ammonium hydroxide. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 100:1˜50:1˜30:1) to give compound 15-3 (17.5 g, 36%). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 15: To the mixture of compound 15-3 (2.2 g, 8.8 mmol, 2.0 eq) and compound 15-4 (2.0 g, 4.4 mmol, 1.0 eq) in dimethylformamide (30 mL) was added potassium tert-butoxide (1.48 g, 13.2 mmol, 3.0 eq) under nitrogen atmosphere. Then the mixture was stirred at 40° C. for 2 h. TLC analysis of the reaction mixture showed partial conversion to the desired product. The mixture was cooled to room temperature and extracted with ethyl acetate and water. The combined organics were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 100:1-50:1) to afford compound 15-5 (550 mg, 20%). 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 15: To the mixture of compound 15-5 (1.0 g, 1.6 mmol, 1.0 eq) in ethanol/water (20 mL/4 mL) was added Fe (446 mg, 8.0 mmol, 5.0 eq) and ammonium chloride (880 mg, 16 mmol, 10.0 eq). Then the mixture was stirred at 80° C. for 2 h. TLC analysis of the reaction mixture showed partial conversion to the desired product. The mixture was filtered and extracted with ethyl acetate (20 mL×3). The combined organics were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 10:1) to afford compound 15-6 (280 mg, 29%). 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 15: To the mixture of compound 15-6 (280 mg, 0.47 mmol, 1.0 eq) in dichloromethane (5 mL) was added compound 15-7 (42.5 mg, 0.47 mmol, 1.0 eq) at 0° C. The mixture was stirred at room temperature for 2 h. TLC analysis of the reaction mixture showed full conversion to the desired product. Then the mixture was quenched with water (20 mL) and extracted with dichloromethane (5 mL×2). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel (dichloromethane: methanol, 10:1) to afford compound 15 (81 mg, 29%) as yellow solid. LCMS: [M+1] + 652.  1 H NMR (400 MHz, CDCl 3 ): δ 11.12 (s, 1H), 9.30 (s, 1H), 8.62 (s, 1H), 8.40 (m, 1H), 8.12 (m, 1H), 7.85 (m, 1H), 7.38 (m, 1H), 7.25 (m, 1H), 7.00 (s, 1H), 6.66 (m, 1H), 6.45 (m, 2H), 6.38-6.35 (m, 4H), 5.71-5.69 (m, 1H), 3.34 (s, 2H), 3.89 (s, 8H), 3.46 (s, 1H), 3.34 (m, 2H), 3.17 (m, 5H) and 1.38-1.35 (m, 8H). 
     Example 12 
     Synthesis of Compound 16 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Compound 16 was synthesized based on synthetic scheme 15. The synthetic process for each of the step is described as below. 
     
       
         
         
             
             
         
       
     
     Step 1 to synthesize compound 16: To a solution of 6-oxabicyclo[3.1.0]hexane (7 g, 83.22 mmol) in i-PrOH (40 mL) was added NH 3 .H 2 O (35.00 g, 249.65 mmol 25% purity). The mixture was stirred at 60° C. for 16 hr in a sealed tube. The mixture was concentrated under reduced pressure to afford trans-2-aminocyclopentanol (26 g, crude) as a brown oil.  1 H NMR (400 MHz, DMSO-d 6 ): δ=3.68-3.53 (m, 1H), 2.88-2.77 (m, 1H), 1.82-1.77 (m, 2H), 1.58-1.53 (m, 2H), 1.44-1.40 (m, 1H), 1.22-1.16 (m, 1H). 
     
       
         
         
             
             
         
       
     
     Step 2 to synthesize compound 16: To a solution of trans-2-aminocyclopentanol(22 g, 217.51 mmol) in THE (220 mL) was added TEA (26.41 g, 261.01 mmol) and Boc 2 O (52.22 g, 239.26 mmol, 54.97 mL, 1.1 eq). The mixture was stirred at 15° C. for 16 hr. The mixture was concentrated under reduced pressure to remove THF. The residue was diluted with EtOAc (20 mL) and extracted with H 2 O (20 mL×3), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜30% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) to afford tert-butyl N-[trans-2-hydroxycyclopentyl]carbamate (14 g, 69.56 mmol, 32% yield) as a white solid.  1 H NMR (400 MHz, DMSO-d 6 ): δ=6.72 (d, J=6.4 Hz, 1H), 4.60 (s, 1H), 3.80-3.75 (m, 1H), 3.49 (br, 1H), 1.86-1.54 (m, 4H), 1.38 (s, 9H), 1.32-1.29 (m, 2H). 
     
       
         
         
             
             
         
       
     
     Step 3 to synthesize compound 16: A mixture of tert-butyl N-[trans-2-hydroxycyclopentyl]carbamate (14 g, 69.56 mmol), isoindoline-1,3-dione (11.26 g, 76.52 mmol), PPh 3  (20.07 g, 76.52 mmol) and DIAD (16.18 g, 80.00 mmol) in THE (150 mL) was degassed and purged with N 2  for 3 times, and then the mixture was stirred at 0° C. for 1 hr. The mixture was concentrated under reduced pressure to remove THF. The residue was diluted with H 2 O (150 mL), and extracted with EtOAc (150 mL×3), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜30% Ethyl acetate/Petroleum ether gradient @ 80 mL/min). The crude product was further re-crystallization from EtOH(100 mL) at 80° C., then the precipitation was filtered, dried to afford tert-butyl N-[cis-2-(1,3-dioxoisoindolin-2-yl)cyclopentyl]carbamate (15 g, 45.40 mmol, 65% yield) as a white solid.  1 H NMR (400 MHz, DMSO-d 6 ): δ=7.83-7.8 (m, 5H), 6.67 (d, J=7.6 Hz, 1H), 4.49-4.45 (m, 1H), 1.92-1.41 (m, 6H), 1.01 (s, 9H). 
     
       
         
         
             
             
         
       
     
     Step 4 to synthesize compound 16: To a solution of tert-butyl N-[cis-2-(1,3-dioxoisoindolin-2-yl)cyclopentyl]carbamate (5 g, 15.13 mmol) in MeOH (50 mL) was added NH 2 NH 2  (709 mg, 16.65 mmol, 80% purity). The mixture was stirred at 50° C. for 1.5 hr. The mixture was concentrated under reduced pressure to remove MeOH. The residue was diluted with H 2 O (50 mL), then extracted with EtOAc (50 mL×3), dried over Na 2 SO 4 , filtered and concentrated to afford tert-butyl N-[cis-2-aminocyclopentyl]carbamate (1.1 g, 5.49 mmol, 36% yield) as a yellow oil. 
     
       
         
         
             
             
         
       
     
     Step 5 to synthesize compound 16: To a solution of N-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(6-methylsulfonylpyrimidin-4-yl)pyridin-2-amine (758 mg, 1.66 mmol) and tert-butyl N-[cis-2-aminocyclopentyl]carbamate (1 g, 4.99 mmol) in DMAc (10 mL) was added DIEA (430 mg, 3.33 mmol). The mixture was stirred at 130° C. for 12 hr. The mixture was diluted with H 2 O (20 mL) and extracted with EtOAc (20 mL×3), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0-30% Ethyl acetate/Petroleum ether gradient @ 40 mL/min) to afford tert-butyl N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]cyclopentyl]carbamate (cis mixture, 500 mg, 0.869 mmol, 52% yield) as a yellow solid. LCMS: t R =1.412 min in 10-80AB_2 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=575.2 [M+H] + . 
     
       
         
         
             
             
         
       
     
     Step 6 to synthesize compound 16: A solution of tert-butyl N-[2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]cyclopentyl]carbamate (500 mg, 0.868 mmol, cis mixture) in HCl/dioxane (4 M, 10 mL) was stirred at 25° C. for 0.5 hr. The mixture was concentrated to afford N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]cyclopentane-1,2-diamine (800 mg, crude) as a white solid. 
     
       
         
         
             
             
         
       
     
     Step 7 to synthesize compound 16: To a solution of N 1 -[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]cyclopentane-1,2-diamine (700 mg, 1.47 mmol, cis mixture) in DCM (10 mL) was added DIEA (190 mg, 1.47 mmol) and prop-2-enoyl chloride (67 mg, 0.736 mmol). The mixture was stirred at 0° C. for 0.5 hr. The residue was diluted with H 2 O (20 mL) and extracted with EtOAc (20 mL×3), dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜10% dichloromethane/Petroleum ether gradient @ 40 mL/min) to give desired product (170 mg, 94% purity) as a white solid, which was further separated by SFC (column: DAICEL CHIRALPAK AD(250 mm*30 mm, 10 um); mobile phase: [0.1% NH 3 .H 2 O ETOH]; B %: 35%-35%, 30 min) to afford (+) N-[cis-2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]cyclopentyl]prop-2-enamide (43.7 mg, 0.081 mmol, 98.85% purity, single cis isomer) and (−) N-[cis-2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]cyclopentyl]prop-2-enamide (46.5 mg, 0.087 mmol, 99.10% purity, single cis isomer) as a white solid. 
     (+)N-[cis-2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]cyclopentyl]prop-2-enamide (the first peak in chiral SFC). LCMS: t R =1.476 min in 10-80AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=529.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=11.09 (s, 1H), 8.48 (s, 1H), 8.04-8.02 (m, 3H), 7.27 (d, J=8.0 Hz, 1H), 6.97 (s, 1H), 6.87-6.83 (m, 2H), 6.17 (s, 1H), 6.05-5.95 (m, 1H), 5.48 (s, 1H), 4.41-4.25 (m, 2H), 3.93 (s, 6H), 2.02-1.57 (m, 6H). Chiral SFC: t R =5.118 min (Instrument column: Chiralpak AD-3 100×4.6 mm I.D., 3 um, Mobile phase: A: CO 2  B:ethanol (0.05% DEA), Gradient: from 5% to 40% of B in 4.5 min and hold 40% for 2.5 min, then 5% of B for 1 min; Flow rate: 2.8 mL/min Column temperature: 40° C.; UV detection: 220 nm), ee %=99%. [α]D 20 =+13 (c=0.10, MeOH). 
     (−)N-[cis-2-[[6-[2-(2,6-dichloro-3,5-dimethoxy-anilino)-3-pyridyl]pyrimidin-4-yl]amino]cyclopentyl]prop-2-enamide (the second peak in chiral SFC). LCMS: t R =1.481 min in 10-80AB_4 min_220&amp;254_Shimadzu.lcm, MS (ESI) m/z=529.2 [M+H] + .  1 H NMR (400 MHz, DMSO-d 6 ): δ=11.09 (s, 1H), 8.48 (s, 1H), 8.04-8.02 (m, 3H), 7.27 (d, J=8.0 Hz, 1H), 6.97 (s, 1H), 6.87-6.83 (m, 2H), 6.16 (s, 1H), 6.05-5.95 (m, 1H), 5.48 (s, 1H), 4.41-4.25 (m, 2H), 3.93 (s, 6H), 2.02-1.57 (m, 6H). Chiral SFC: t R =6.002 min (Instrument column: Chiralpak AD-3 100×4.6 mm I.D., 3 um, Mobile phase: A: CO 2  B:ethanol (0.05% DEA), Gradient: from 5% to 40% of B in 4.5 min and hold 40% for 2.5 min, then 5% of B for 1 min; Flow rate: 2.8 mL/min Column temperature: 40° C.; UV detection: 220 nm), ee %=99.1%. [α]D 20 =−13 (c=0.10, MeOH). 
     Example 13 
     Evalation of the In Vitro Efficacy of FGFR Inhibitors 
     
       
         
         
             
             
         
       
     
     Table 2 below compares the properties of inventive compound 1 and control compound 5, which indicates that compound 1 exhibits superior properties in solubility, permeability, mouse plasma stability, mouse liver microsome stability, in vivo exposure, and bioavailability than control compound 5. The inventive compound 1 improves the FGFR4-selective inhibitory effect. More importantly, the plasma stability of the inventive compound is significantly improved. Also, control compound 5 has poor solubility in the solution of 5% DMSO and 95% of (20% HPBC in PBS). The inventive compound 1, on the other hand, exhibits a much-improved solubility which facilitates its administration. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Comparison of the properties between inventive 
               
               
                 compound 1 and control compound 5. 
               
            
           
           
               
               
               
            
               
                 Compound 
                 Compound 1 
                 Compound 5 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Molecular weight 
                 530.12 
                 550.13 
               
               
                 s + LogP 
                 3.13 
                 5.08 
               
               
                 s + LogD 7.4 
                 3.12 
                 5.08 
               
               
                 MDCK Permeability Papp,  
                 25.8 
                 11.4 
               
               
                 A-B (1X10 −6  cm/s) 
                   
                   
               
               
                 Protein binding (%) 
                 92 
                 — 
               
               
                 T_PSA Å 2   
                 119.52 
                 110.29 
               
               
                 IC 50  towards FGFR1 (nM) 
                 1280 
                 &gt;30000 
               
               
                 IC 50  towards FGFR2 (nM) 
                 1870 
                 &gt;30000 
               
               
                 IC 50  towards FGFR3 (nM) 
                 4440 
                 &gt;30000 
               
               
                 IC 50  towards FGFR4 (nM) 
                 20 
                 4.1 
               
               
                 Hepatocyte Clin Ms 
                 43.63 ± 1.30 
                 41.70 ± 1.73 
               
               
                 (mL/min/10 6  cells) (SE) 
                   
                   
               
               
                 Ms Plasma Stability 
                 1147.5 ± 347.0 
                 221.2 ± 55.7 
               
               
                 t 1/2  (min)(SE) 
                   
                   
               
               
                 CL (L/h/kg)|Vss (L/kg)| 
                 1.6|0.88l0.52l20.9 
                 0.84l1.53l15(?)l8.0 
               
               
                 t 1/2  (h)|% F 
               
               
                   
               
            
           
         
       
     
     Referring to  FIGS. 2 and 3 , the inventive compound 5 also exhibits an non-obvious improvement of pharmacokinetic data when administered into mice. Table 3 below summarizes the critical pharmacokinetic data from these experiments. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Pharmacokinetic data of inventive compound 1 and 
               
               
                 control compound 5. 
               
            
           
           
               
               
            
               
                   
                 Compound 
               
            
           
           
               
               
               
            
               
                   
                 Compound 1 
                 Compound 5 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Route 
                 IP 
                 IV 
                 PO 
                 IP 
                 IV 
                 PO 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Dose 
                 10 
                 1 
                 5 
                 10 
                 5 
                 100 
               
               
                 (mg/kg) 
                   
                   
                   
                   
                   
                   
               
               
                 FIGS. 
                 FIG.  
                 FIG.  
                 FIG.  
                 FIG.  
                 FIG.  
                 FIG.  
               
               
                   
                 2A 
                 2B 
                 2B 
                 3A 
                 3B 
                 3B 
               
               
                 T max  (hr) 
                 0.25 
                 0.083 
                 3.17 
                 0.25 
                 0.083 
                 6.67 
               
               
                 C max   
                 14867 
                 849 
                 119 
                 865 
                 470 
                 180 
               
               
                 (ng/mL) 
                   
                   
                   
                   
                   
                   
               
               
                 T 1/2  (hr) 
                 2.81 
                 0.522 
                 2.73 
                 1.23 
                 15.1 
                 — 
               
               
                 MRT last   
                 0.67 
                 0.515 
                 3.42 
                 1.57 
                 7.71 
                 6.1 
               
               
                 (hr) 
                   
                   
                   
                   
                   
                   
               
               
                 MRT inf  (hr) 
                 0.67 
                 0.537 
                 4.02 
                 1.66 
                 18.5 
                 — 
               
               
                 AUC last   
                 9608 
                 618 
                 465 
                 1270 
                 896 
                 1450 
               
               
                 (hr*ng/mL) 
                   
                   
                   
                   
                   
                   
               
               
                 AUC inf   
                 9609 
                 621 
                 648 
                 1280 
                 1240 
                 — 
               
               
                 (hr*ng/mL) 
                   
                   
                   
                   
                   
                   
               
               
                 Cl 
                 — 
                 1632 
                 — 
                 — 
                 837 
                 8.09 
               
               
                 (mL/hr/kg) 
                   
                   
                   
                   
                   
                   
               
               
                 Vss 
                 — 
                 876 
                 — 
                 — 
                 15300 
                 — 
               
               
                 (mL/kg) 
                   
                   
                   
                   
                   
                   
               
               
                 F (%) 
                 — 
                 — 
                 20.9 
                 — 
                 — 
                 8.09 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 FGFR inhibition data of the disclosed compounds. 
               
            
           
           
               
               
               
               
               
               
            
               
                 Compound 
                   
                 FGFR1 
                 FGFR2 
                 FGFR3 
                 FGFR4 
               
               
                 No. 
                 Molecular Structure 
                 Inhibition 
                 Inhibition 
                 Inhibition 
                 inhibition 
               
               
                   
               
               
                 Compound 1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 — 
                 — 
                 ++ 
               
               
                   
               
               
                 Compound 2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ++ 
                 + 
                 + 
                 +++ 
               
               
                   
               
               
                 Compound 3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ND 
                 ND 
                 ND 
                 + 
               
               
                   
               
               
                 Compound 4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ND 
                 ND 
                 ND 
                 ++ 
               
               
                   
               
               
                 Compound 5 (Control) 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 — 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 + 
                 + 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 + 
                 + 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 + 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 + 
                 + 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 10  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 — 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 — 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 + 
                 + 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ND 
                 ND 
                 ND 
                 — 
               
               
                   
               
               
                 Compound 14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 — 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 — 
                 — 
                 — 
                 +++ 
               
               
                   
               
               
                 Compound 16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ND 
                 ND 
                 ND 
                 + 
               
               
                   
               
               
                 The evaluation standards of IC 50  values against the kinases in the table are shown below. 
               
               
                 +++ below or equal to 10 nM 
               
               
                 ++ between 10 and 100 nM 
               
               
                 + between 100 and 1000 nM 
               
               
                 — above or equal 1000 nM 
               
               
                 ND Not determined 
               
            
           
         
       
     
     The FGFR inhibition data of the disclosed compounds are shown in Table 4. Compound 5 is used as a control. 
     
       
         
           
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 FGFR sequences. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 SEQ ID 
                 FGFR1 
                 AGATGCAGGGGCGCAAACGCCAAAGGAGACCAGGCTGTAGGAAGAGAAGGGCAGAGC 
               
               
                 NO: 1 
                 isoform 1 
                 GCCGGACAGCTCGGCCCGCTCCCCGTCCTTTGGGGCCGCGGCTGGGGAACTACAAGG 
               
               
                   
                 Nucleic acid 
                 CCCAGCAGGCAGCTGCAGGGGGCGGAGGCGGAGGAGGGACCAGCGCGGGTGGGAGTG 
               
               
                   
                 sequence 
                 AGAGAGCGAGCCCTCGCGCCCCGCCGGCGCATAGCGCTCGGAGCGCTCTTGCGGCCA 
               
               
                   
                   
                 CAGGCGCGGCGTCCTCGGCGGCGGGCGGCAGCTAGCGGGAGCCGGGACGCCGGTGCA 
               
               
                   
                   
                 GCCGCAGCGCGCGGAGGAACCCGGGTGTGCCGGGAGCTGGGCGGCCACGTCCGGACG 
               
               
                   
                   
                 GGACCGAGACCCCTCGTAGCGCATTGCGGCGACCTCGCCTTCCCCGGCCGCGAGCGC 
               
               
                   
                   
                 GCCGCTGCTTGAAAAGCCGCGGAACCCAAGGACTTTTCTCCGGTCCGAGCTCGGGGC 
               
               
                   
                   
                 GCCCCGCAGGGCGCACGGTACCCGTGCTGCAGTCGGGCACGCCGCGGCGCCGGGGCC 
               
               
                   
                   
                 TCCGCAGGGCGATGGAGCCCGGTCTGCAAGGAAAGTGAGGCGCCGCCGCTGCGTTCT 
               
               
                   
                   
                 GGAGGAGGGGGGCACAAGGTCTGGAGACCCCGGGTGGCGGACGGGAGCCCTCCCCCC 
               
               
                   
                   
                 GCCCCGCCTCCGGGGCACCAGCTCCGGCTCCATTGTTCCCGCCCGGGCTGGAGGCGC 
               
               
                   
                   
                 CGAGCACCGAGCGCCGCCGGGAGTCGAGCGCCGGCCGCGGAGCTCTTGCGACCCCGC 
               
               
                   
                   
                 CAGGACCCGAACAGAGCCCGGGGGCGGCGGGCCGGAGCCGGGGACGCGGGCACACGC 
               
               
                   
                   
                 CCGCTCGCACAAGCCACGGCGGACTCTCCCGAGGCGGAACCTCCACGCCGAGCGAGG 
               
               
                   
                   
                 GTCAGTTTGAAAAGGAGGATCGAGCTCACTGTGGAGTATCCATGGAGATGTGGAGCC 
               
               
                   
                   
                 TTGTCACCAACCTCTAACTGCAGAACTGGGATGTGGAGCTGGAAGTGCCTCCTCTTC 
               
               
                   
                   
                 TGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCCGTCCCCGACCTTGCCT 
               
               
                   
                   
                 GAACAAGCCCAGCCCTGGGGAGCCCCTGTGGAAGTGGAGTCCTTCCTGGTCCACCCC 
               
               
                   
                   
                 GGTGACCTGCTGCAGCTTCGCTGTCGGCTGCGGGACGATGTGCAGAGCATCAACTGG 
               
               
                   
                   
                 CTGCGGGACGGGGTGCAGCTGGCGGAAAGCAACCGCACCCGCATCACAGGGGAGGAG 
               
               
                   
                   
                 GTGGAGGTGCAGGACTCCGTGCCCGCAGACTCCGGCCTCTATGCTTGCGTAACCAGC 
               
               
                   
                   
                 AGCCCCTCGGGCAGTGACACCACCTACTTCTCCGTCAATGTTTCAGATGCTCTCCCC 
               
               
                   
                   
                 TCCTCGGAGGATGATGATGATGATGATGACTCCTCTTCAGAGGAGAAAGAAACAGAT 
               
               
                   
                   
                 AACACCAAACCAAACCGTATGCCCGTAGCTCCATATTGGACATCCCCAGAAAAGATG 
               
               
                   
                   
                 GAAAAGAAATTGCATGCAGTGCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCC 
               
               
                   
                   
                 AGTGGGACCCCAAACCCCACACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAACCT 
               
               
                   
                   
                 GACCACAGAATTGGAGGCTACAAGGTCCGTTATGCCACCTGGAGCATCATAATGGAC 
               
               
                   
                   
                 TCTGTGGTGCCCTCTGACAAGGGCAACTACACCTGCATTGTGGAGAATGAGTACGGC 
               
               
                   
                   
                 AGCATCAACCACACATACCAGCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATC 
               
               
                   
                   
                 CTGCAAGCAGGGTTGCCCGCCAACAAAACAGTGGCCCTGGGTAGCAACGTGGAGTTC 
               
               
                   
                   
                 ATGTGTAAGGTGTACAGTGACCCGCAGCCGCACATCCAGTGGCTAAAGCACATCGAG 
               
               
                   
                   
                 GTGAATGGGAGCAAGATTGGCCCAGACAACCTGCCTTATGTCCAGATCTTGAAGACT 
               
               
                   
                   
                 GCTGGAGTTAATACCACCGACAAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCC 
               
               
                   
                   
                 TTTGAGGACGCAGGGGAGTATACGTGCTTGGCGGGTAACTCTATCGGACTCTCCCAT 
               
               
                   
                   
                 CACTCTGCATGGTTGACCGTTCTGGAAGCCCTGGAAGAGAGGCCGGCAGTGATGACC 
               
               
                   
                   
                 TCGCCCCTGTACCTGGAGATCATCATCTATTGCACAGGGGCCTTCCTCATCTCCTGC 
               
               
                   
                   
                 ATGGTGGGGTCGGTCATCGTCTACAAGATGAAGAGTGGTACCAAGAAGAGTGACTTC 
               
               
                   
                   
                 CACAGCCAGATGGCTGTGCACAAGCTGGCCAAGAGCATCCCTCTGCGCAGACAGGTA 
               
               
                   
                   
                 ACAGTGTCTGCTGACTCCAGTGCATCCATGAACTCTGGGGTTCTTCTGGTTCGGCCA 
               
               
                   
                   
                 TCACGGCTCTCCTCCAGTGGGACTCCCATGCTAGCAGGGGTCTCTGAGTATGAGCTT 
               
               
                   
                   
                 CCCGAAGACCCTCGCTGGGAGCTGCCTCGGGACAGACTGGTCTTAGGCAAACCCCTG 
               
               
                   
                   
                 GGAGAGGGCTGCTTTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAGGAC 
               
               
                   
                   
                 AAACCCAACCGTGTGACCAAAGTGGCTGTGAAGATGTTGAAGTCGGACGCAACAGAG 
               
               
                   
                   
                 AAAGACTTGTCAGACCTGATCTCAGAAATGGAGATGATGAAGATGATCGGGAAGCAT 
               
               
                   
                   
                 AAGAATATCATCAACCTGCTGGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATC 
               
               
                   
                   
                 GTGGAGTATGCCTCCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCCCCA 
               
               
                   
                   
                 GGGCTGGAATACTGCTACAACCCCAGCCACAACCCAGAGGAGCAGCTCTCCTCCAAG 
               
               
                   
                   
                 GACCTGGTGTCCTGCGCCTACCAGGTGGCCCGAGGCATGGAGTATCTGGCCTCCAAG 
               
               
                   
                   
                 AAGTGCATACACCGAGACCTGGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTG 
               
               
                   
                   
                 ATGAAGATAGCAGACTTTGGCCTCGCACGGGACATTCACCACATCGACTACTATAAA 
               
               
                   
                   
                 AAGACAACCAACGGCCGACTGCCTGTGAAGTGGATGGCACCCGAGGCATTATTTGAC 
               
               
                   
                   
                 CGGATCTACACCCACCAGAGTGATGTGTGGTCTTTCGGGGTGCTCCTGTGGGAGATC 
               
               
                   
                   
                 TTCACTCTGGGCGGCTCCCCATACCCCGGTGTGCCTGTGGAGGAACTTTTCAAGCTG 
               
               
                   
                   
                 CTGAAGGAGGGTCACCGCATGGACAAGCCCAGTAACTGCACCAACGAGCTGTACATG 
               
               
                   
                   
                 ATGATGCGGGACTGCTGGCATGCAGTGCCCTCACAGAGACCCACCTTCAAGCAGCTG 
               
               
                   
                   
                 GTGGAAGACCTGGACCGCATCGTGGCCTTGACCTCCAACCAGGAGTACCTGGACCTG 
               
               
                   
                   
                 TCCATGCCCCTGGACCAGTACTCCCCCAGCTTTCCCGACACCCGGAGCTCTACGTGC 
               
               
                   
                   
                 TCCTCAGGGGAGGATTCCGTCTTCTCTCATGAGCCGCTGCCCGAGGAGCCCTGCCTG 
               
               
                   
                   
                 CCCCGACACCCAGCCCAGCTTGCCAATGGCGGACTCAAACGCCGCTGACTGCCACCC 
               
               
                   
                   
                 ACACGCCCTCCCCAGACTCCACCGTCAGCTGTAACCCTCACCCACAGCCCCTGCTGG 
               
               
                   
                   
                 GCCCACCACCTGTCCGTCCCTGTCCCCTTTCCTGCTGGCAGGAGCCGGCTGCCTACC 
               
               
                   
                   
                 AGGGGCCTTCCTGTGTGGCCTGCCTTCACCCCACTCAGCTCACCTCTCCCTCCACCT 
               
               
                   
                   
                 CCTCTCCACCTGCTGGTGAGAGGTGCAAAGAGGCAGATCTTTGCTGCCAGCCACTTC 
               
               
                   
                   
                 ATCCCCTCCCAGATGTTGGACCAACACCCCTCCCTGCCACCAGGCACTGCCTGGAGG 
               
               
                   
                   
                 GCAGGGAGTGGGAGCCAATGAACAGGCATGCAAGTGAGAGCTTCCTGAGCTTTCTCC 
               
               
                   
                   
                 TGTCGGTTTGGTCTGTTTTGCCTTCACCCATAAGCCCCTCGCACTCTGGTGGCAGGT 
               
               
                   
                   
                 GCCTTGTCCTCAGGGCTACAGCAGTAGGGAGGTCAGTGCTTCGTGCCTCGATTGAAG 
               
               
                   
                   
                 GTGACCTCTGCCCCAGATAGGTGGTGCCAGTGGCTTATTAATTCCGATACTAGTTTG 
               
               
                   
                   
                 CTTTGCTGACCAAATGCCTGGTACCAGAGGATGGTGAGGCGAAGGCCAGGTTGGGGG 
               
               
                   
                   
                 CAGTGTTGTGGCCCTGGGGCCCAGCCCCAAACTGGGGGCTCTGTATATAGCTATGAA 
               
               
                   
                   
                 GAAAACACAAAGTGTATAAATCTGAGTATATATTTACATGTCTTTTTAAAAGGGTCG 
               
               
                   
                   
                 TTACCAGAGATTTACCCATCGGGTAAGATGCTCCTGGTGGCTGGGAGGCATCAGTTG 
               
               
                   
                   
                 CTATATATTAAAAACAAAAAAGAAAAAAAAGGAAAATGTTTTTAAAAAGGTCATATA 
               
               
                   
                   
                 TTTTTTGCTACTTTTGCTGTTTTATTTTTTTAAATTATGTTCTAAACCTATTTTCAG 
               
               
                   
                   
                 TTTAGGTCCCTCAATAAAAATTGCTGCTGCTTCATTTATCTATGGGCTGTATGAAAA 
               
               
                   
                   
                 GGGTGGGAATGTCCACTGGAAAGAAGGGACACCCACGGGCCCTGGGGCTAGGTCTGT 
               
               
                   
                   
                 CCCGAGGGCACCGCATGCTCCCGGCGCAGGTTCCTTGTAACCTCTTCTTCCTAGGTC 
               
               
                   
                   
                 CTGCACCCAGACCTCACGACGCACCTCCTGCCTCTCCGCTGCTTTTGGAAAGTCAGA 
               
               
                   
                   
                 AAAAGAAGATGTCTGCTTCGAGGGCAGGAACCCCATCCATGCAGTAGAGGCGCTGGG 
               
               
                   
                   
                 CAGAGAGTCAAGGCCCAGCAGCCATCGACCATGGATGGTTTCCTCCAAGGAAACCGG 
               
               
                   
                   
                 TGGGGTTGGGCTGGGGAGGGGGCACCTACCTAGGAATAGCCACGGGGTAGAGCTACA 
               
               
                   
                   
                 GTGATTAAGAGGAAAGCAAGGGCGCGGTTGCTCACGCCTGTAATCCCAGCACTTTGG 
               
               
                   
                   
                 GACACCGAGGTGGGCAGATCACTTCAGGTCAGGAGTTTGAGACCAGCCTGGCCAACT 
               
               
                   
                   
                 TAGTGAAACCCCATCTCTACTAAAAATGCAAAAATTATCCAGGCATGGTGGCACACG 
               
               
                   
                   
                 CCTGTAATCCCAGCTCCACAGGAGGCTGAGGCAGAATCCCTTGAAGCTGGGAGGCGG 
               
               
                   
                   
                 AGGTTGCAGTGAGCCGAGATTGCGCCATTGCACTCCAGCCTGGGCAACAGAGAAAAC 
               
               
                   
                   
                 AAAAAGGAAAACAAATGATGAAGGTCTGCAGAAACTGAAACCCAGACATGTGTCTGC 
               
               
                   
                   
                 CCCCTCTATGTGGGCATGGTTTTGCCAGTGCTTCTAAGTGCAGGAGAACATGTCACC 
               
               
                   
                   
                 TGAGGCTAGTTTTGCATTCAGGTCCCTGGCTTCGTTTCTTGTTGGTATGCCTCCCCA 
               
               
                   
                   
                 GATCGTCCTTCCTGTATCCATGTGACCAGACTGTATTTGTTGGGACTGTCGCAGATC 
               
               
                   
                   
                 TTGGCTTCTTACAGTTCTTCCTGTCCAAACTCCATCCTGTCCCTCAGGAACGGGGGG 
               
               
                   
                   
                 AAAATTCTCCGAATGTTTTTGGTTTTTTGGCTGCTTGGAATTTACTTCTGCCACCTG 
               
               
                   
                   
                 CTGGTCATCACTGTCCTCACTAAGTGGATTCTGGCTCCCCCGTACCTCATGGCTCAA 
               
               
                   
                   
                 ACTACCACTCCTCAGTCGCTATATTAAAGCTTATATTTTGCTGGATTACTGCTAAAT 
               
               
                   
                   
                 ACAAAAGAAAGTTCAATATGTTTTCATTTCTGTAGGGAAAATGGGATTGCTGCTTTA 
               
               
                   
                   
                 AATTTCTGAGCTAGGGATTTTTTGGCAGCTGCAGTGTTGGCGACTATTGTAAAATTC 
               
               
                   
                   
                 TCTTTGTTTCTCTCTGTAAATAGCACCTGCTAACATTACAATTTGTATTTATGTTTA 
               
               
                   
                   
                 AAGAAGGCATCATTTGGTGAACAGAACTAGGAAATGAATTTTTAGCTCTTAAAAGCA 
               
               
                   
                   
                 TTTGCTTTGAGACCGCACAGGAGTGTCTTTCCTTGTAAAACAGTGATGATAATTTCT 
               
               
                   
                   
                 GCCTTGGCCCTACCTTGAAGCAATGTTGTGTGAAGGGATGAAGAATCTAAAAGTCTT 
               
               
                   
                   
                 CATAAGTCCTTGGGAGAGGTGCTAGAAAAATATAAGGCACTATCATAATTACAGTGA 
               
               
                   
                   
                 TGTCCTTGCTGTTACTACTCAAATCACCCACAAATTTCCCCAAAGACTGCGCTAGCT 
               
               
                   
                   
                 GTCAAATAAAAGACAGTGAAATTGACCTG 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRL 
               
               
                 NO: 2 
                 isoform 1 
                 RDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYF 
               
               
                   
                 Amino acid 
                 SVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAA 
               
               
                   
                 sequence 
                 KTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNY 
               
               
                   
                   
                 TCIVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQP 
               
               
                   
                   
                 HIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCL 
               
               
                   
                   
                 AGNSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKM 
               
               
                   
                   
                 KSGTKKSDFHSQMAVHKLAKSIPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPM 
               
               
                   
                   
                 LAGVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAV 
               
               
                   
                   
                 KMLKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR   
               
               
                   
                   
                 EYLQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAAR 
               
               
                   
                   
                 NVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVW 
               
               
                   
                   
                 SFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVP 
               
               
                   
                   
                 SQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSH 
               
               
                   
                   
                 EPLPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 GCCGGCGCATAGCGCTCGGAGCGCTCTTGCGGCCACAGGCGCGGCGTCCTCGGCGGC 
               
               
                 NO: 3 
                 isoform 2 
                 GGGCGGCAGCTAGCGGGAGCCGGGACGCCGGTGCAGCCGCAGCGCGCGGAGGAACCC 
               
               
                   
                 Nucleic acid 
                 GGGTGTGCCGGGAGCTGGGCGGCCACGTCCGGACGGGACCGAGACCCCTCGTAGCGC 
               
               
                   
                 sequence 
                 ATTGCGGCGACCTCGCCTTCCCCGGCCGCGAGCGCGCCGCTGCTTGAAAAGCCGCGG 
               
               
                   
                   
                 AACCCAAGGACTTTTCTCCGGTCCGAGCTCGGGGCGCCCCGCAGGGCGCACGGTACC 
               
               
                   
                   
                 CGTGCTGCAGTCGGGCACGCCGCGGCGCCGGGGCCTCCGCAGGGCGATGGAGCCCGG 
               
               
                   
                   
                 TCTGCAAGGAAAGTGAGGCGCCGCCGCTGCGTTCTGGAGGAGGGGGGCACAAGGTCT 
               
               
                   
                   
                 GGAGACCCCGGGTGGCGGACGGGAGCCCTCCCCCCGCCCCGCCTCCGGGGCACCAGC 
               
               
                   
                   
                 TCCGGCTCCATTGTTCCCGCCCGGGCTGGAGGCGCCGAGCACCGAGCGCCGCCGGGA 
               
               
                   
                   
                 GTCGAGCGCCGGCCGCGGAGCTCTTGCGACCCCGCCAGGACCCGAACAGAGCCCGGG 
               
               
                   
                   
                 GGCGGCGGGCCGGAGCCGGGGACGCGGGCACACGCCCGCTCGCACAAGCCACGGCGG 
               
               
                   
                   
                 ACTCTCCCGAGGCGGAACCTCCACGCCGAGCGAGGGTCAGTTTGAAAAGGAGGATCG 
               
               
                   
                   
                 AGCTCACTGTGGAGTATCCATGGAGATGTGGAGCCTTGTCACCAACCTCTAACTGCA 
               
               
                   
                   
                 GAACTGGGATGTGGAGCTGGAAGTGCCTCCTCTTCTGGGCTGTGCTGGTCACAGCCA 
               
               
                   
                   
                 CACTCTGCACCGCTAGGCCGTCCCCGACCTTGCCTGAACAAGCCCAGCCCTGGGGAG 
               
               
                   
                   
                 CCCCTGTGGAAGTGGAGTCCTTCCTGGTCCACCCCGGTGACCTGCTGCAGCTTCGCT 
               
               
                   
                   
                 GTCGGCTGCGGGACGATGTGCAGAGCATCAACTGGCTGCGGGACGGGGTGCAGCTGG 
               
               
                   
                   
                 CGGAAAGCAACCGCACCCGCATCACAGGGGAGGAGGTGGAGGTGCAGGACTCCGTGC 
               
               
                   
                   
                 CCGCAGACTCCGGCCTCTATGCTTGCGTAACCAGCAGCCCCTCGGGCAGTGACACCA 
               
               
                   
                   
                 CCTACTTCTCCGTCAATGTTTCAGATGCTCTCCCCTCCTCGGAGGATGATGATGATG 
               
               
                   
                   
                 ATGATGACTCCTCTTCAGAGGAGAAAGAAACAGATAACACCAAACCAAACCCCGTAG 
               
               
                   
                   
                 CTCCATATTGGACATCCCCAGAAAAGATGGAAAAGAAATTGCATGCAGTGCCGGCTG 
               
               
                   
                   
                 CCAAGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACCCCAAACCCCACACTGCGCT 
               
               
                   
                   
                 GGTTGAAAAATGGCAAAGAATTCAAACCTGACCACAGAATTGGAGGCTACAAGGTCC 
               
               
                   
                   
                 GTTATGCCACCTGGAGCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACT 
               
               
                   
                   
                 ACACCTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCAGCTGGATG 
               
               
                   
                   
                 TCGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGCCAACAAAA 
               
               
                   
                   
                 CAGTGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGACCCGCAGC 
               
               
                   
                   
                 CGCACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACA 
               
               
                   
                   
                 ACCTGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGACAAAGAGA 
               
               
                   
                   
                 TGGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACGTGCT 
               
               
                   
                   
                 TGGCGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAAG 
               
               
                   
                   
                 CCCTGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCT 
               
               
                   
                   
                 ATTGCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGA 
               
               
                   
                   
                 TGAAGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGG 
               
               
                   
                   
                 CCAAGAGCATCCCTCTGCGCAGACAGGTAACAGTGTCTGCTGACTCCAGTGCATCCA 
               
               
                   
                   
                 TGAACTCTGGGGTTCTTCTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCA 
               
               
                   
                   
                 TGCTAGCAGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTC 
               
               
                   
                   
                 GGGACAGACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGT 
               
               
                   
                   
                 TGGCAGAGGCTATCGGGCTGGACAAGGACAAACCCAACCGTGTGACCAAAGTGGCTG 
               
               
                   
                   
                 TGAAGATGTTGAAGTCGGACGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAA 
               
               
                   
                   
                 TGGAGATGATGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCTGGGGGCCT 
               
               
                   
                   
                 GCACGCAGGATGGTCCCTTGTATGTCATCGTGGAGTATGCCTCCAAGGGCAACCTGC 
               
               
                   
                   
                 GGGAGTACCTGCAGGCCCGGAGGCCCCCAGGGCTGGAATACTGCTACAACCCCAGCC 
               
               
                   
                   
                 ACAACCCAGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGG 
               
               
                   
                   
                 CCCGAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACCTGGCAGCCA 
               
               
                   
                   
                 GGAATGTCCTGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTTGGCCTCGCAC 
               
               
                   
                   
                 GGGACATTCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGA 
               
               
                   
                   
                 AGTGGATGGCACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGATGTGT 
               
               
                   
                   
                 GGTCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCCG 
               
               
                   
                   
                 GTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGC 
               
               
                   
                   
                 CCAGTAACTGCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGC 
               
               
                   
                   
                 CCTCACAGAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCT 
               
               
                   
                   
                 TGACCTCCAACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCA 
               
               
                   
                   
                 GCTTTCCCGACACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTC 
               
               
                   
                   
                 ATGAGCCGCTGCCCGAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATG 
               
               
                   
                   
                 GCGGACTCAAACGCCGCTGACTGCCACCCACACGCCCTCCCCAGACTCCACCGTCAG 
               
               
                   
                   
                 CTGTAACCCTCACCCACAGCCCCTGCTGGGCCCACCACCTGTCCGTCCCTGTCCCCT 
               
               
                   
                   
                 TTCCTGCTGGCAGGAGCCGGCTGCCTACCAGGGGCCTTCCTGTGTGGCCTGCCTTCA 
               
               
                   
                   
                 CCCCACTCAGCTCACCTCTCCCTCCACCTCCTCTCCACCTGCTGGTGAGAGGTGCAA 
               
               
                   
                   
                 AGAGGCAGATCTTTGCTGCCAGCCACTTCATCCCCTCCCAGATGTTGGACCAACACC 
               
               
                   
                   
                 CCTCCCTGCCACCAGGCACTGCCTGGAGGGCAGGGAGTGGGAGCCAATGAACAGGCA 
               
               
                   
                   
                 TGCAAGTGAGAGCTTCCTGAGCTTTCTCCTGTCGGTTTGGTCTGTTTTGCCTTCACC 
               
               
                   
                   
                 CATAAGCCCCTCGCACTCTGGTGGCAGGTGCCTTGTCCTCAGGGCTACAGCAGTAGG 
               
               
                   
                   
                 GAGGTCAGTGCTTCGTGCCTCGATTGAAGGTGACCTCTGCCCCAGATAGGTGGTGCC 
               
               
                   
                   
                 AGTGGCTTATTAATTCCGATACTAGTTTGCTTTGCTGACCAAATGCCTGGTACCAGA 
               
               
                   
                   
                 GGATGGTGAGGCGAAGGCCAGGTTGGGGGCAGTGTTGTGGCCCTGGGGCCCAGCCCC 
               
               
                   
                   
                 AAACTGGGGGCTCTGTATATAGCTATGAAGAAAACACAAAGTGTATAAATCTGAGTA 
               
               
                   
                   
                 TATATTTACATGTCTTTTTAAAAGGGTCGTTACCAGAGATTTACCCATCGGGTAAGA 
               
               
                   
                   
                 TGCTCCTGGTGGCTGGGAGGCATCAGTTGCTATATATTAAAAACAAAAAAGAAAAAA 
               
               
                   
                   
                 AAGGAAAATGTTTTTAAAAAGGTCATATATTTTTTGCTACTTTTGCTGTTTTATTTT 
               
               
                   
                   
                 TTTAAATTATGTTCTAAACCTATTTTCAGTTTAGGTCCCTCAATAAAAATTGCTGCT 
               
               
                   
                   
                 GCTTCATTTATCTATGGGCTGTATGAAAAGGGTGGGAATGTCCACTGGAAAGAAGGG 
               
               
                   
                   
                 ACACCCACGGGCCCTGGGGCTAGGTCTGTCCCGAGGGCACCGCATGCTCCCGGCGCA 
               
               
                   
                   
                 GGTTCCTTGTAACCTCTTCTTCCTAGGTCCTGCACCCAGACCTCACGACGCACCTCC 
               
               
                   
                   
                 TGCCTCTCCGCTGCTTTTGGAAAGTCAGAAAAAGAAGATGTCTGCTTCGAGGGCAGG 
               
               
                   
                   
                 AACCCCATCCATGCAGTAGAGGCGCTGGGCAGAGAGTCAAGGCCCAGCAGCCATCGA 
               
               
                   
                   
                 CCATGGATGGTTTCCTCCAAGGAAACCGGTGGGGTTGGGCTGGGGAGGGGGCACCTA 
               
               
                   
                   
                 CCTAGGAATAGCCACGGGGTAGAGCTACAGTGATTAAGAGGAAAGCAAGGGCGCGGT 
               
               
                   
                   
                 TGCTCACGCCTGTAATCCCAGCACTTTGGGACACCGAGGTGGGCAGATCACTTCAGG 
               
               
                   
                   
                 TCAGGAGTTTGAGACCAGCCTGGCCAACTTAGTGAAACCCCATCTCTACTAAAAATG 
               
               
                   
                   
                 CAAAAATTATCCAGGCATGGTGGCACACGCCTGTAATCCCAGCTCCACAGGAGGCTG 
               
               
                   
                   
                 AGGCAGAATCCCTTGAAGCTGGGAGGCGGAGGTTGCAGTGAGCCGAGATTGCGCCAT 
               
               
                   
                   
                 TGCACTCCAGCCTGGGCAACAGAGAAAACAAAAAGGAAAACAAATGATGAAGGTCTG 
               
               
                   
                   
                 CAGAAACTGAAACCCAGACATGTGTCTGCCCCCTCTATGTGGGCATGGTTTTGCCAG 
               
               
                   
                   
                 TGCTTCTAAGTGCAGGAGAACATGTCACCTGAGGCTAGTTTTGCATTCAGGTCCCTG 
               
               
                   
                   
                 GCTTCGTTTCTTGTTGGTATGCCTCCCCAGATCGTCCTTCCTGTATCCATGTGACCA 
               
               
                   
                   
                 GACTGTATTTGTTGGGACTGTCGCAGATCTTGGCTTCTTACAGTTCTTCCTGTCCAA 
               
               
                   
                   
                 ACTCCATCCTGTCCCTCAGGAACGGGGGGAAAATTCTCCGAATGTTTTTGGTTTTTT 
               
               
                   
                   
                 GGCTGCTTGGAATTTACTTCTGCCACCTGCTGGTCATCACTGTCCTCACTAAGTGGA 
               
               
                   
                   
                 TTCTGGCTCCCCCGTACCTCATGGCTCAAACTACCACTCCTCAGTCGCTATATTAAA 
               
               
                   
                   
                 GCTTATATTTTGCTGGATTACTGCTAAATACAAAAGAAAGTTCAATATGTTTTCATT 
               
               
                   
                   
                 TCTGTAGGGAAAATGGGATTGCTGCTTTAAATTTCTGAGCTAGGGATTTTTTGGCAG 
               
               
                   
                   
                 CTGCAGTGTTGGCGACTATTGTAAAATTCTCTTTGTTTCTCTCTGTAAATAGCACCT 
               
               
                   
                   
                 GCTAACATTACAATTTGTATTTATGTTTAAAGAAGGCATCATTTGGTGAACAGAACT 
               
               
                   
                   
                 AGGAAATGAATTTTTAGCTCTTAAAAGCATTTGCTTTGAGACCGCACAGGAGTGTCT 
               
               
                   
                   
                 TTCCTTGTAAAACAGTGATGATAATTTCTGCCTTGGCCCTACCTTGAAGCAATGTTG 
               
               
                   
                   
                 TGTGAAGGGATGAAGAATCTAAAAGTCTTCATAAGTCCTTGGGAGAGGTGCTAGAAA 
               
               
                   
                   
                 AATATAAGGCACTATCATAATTACAGTGATGTCCTTGCTGTTACTACTCAAATCACC 
               
               
                   
                   
                 CACAAATTTCCCCAAAGACTGCGCTAGCTGTCAAATAAAAGACAGTGAAATTGACCT 
               
               
                   
                   
                 GA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRL 
               
               
                 NO: 4 
                 isoform 2 
                 RDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYF 
               
               
                   
                 Amino acid 
                 SVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNPVAPYWTSPEKMEKKLHAVPAAKT 
               
               
                   
                 sequence 
                 VKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTC 
               
               
                   
                   
                 IVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHI 
               
               
                   
                   
                 QWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAG 
               
               
                   
                   
                 NSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKS 
               
               
                   
                   
                 GTKKSDFHSQMAVHKLAKSIPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLA 
               
               
                   
                   
                 GVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKM 
               
               
                   
                   
                 LKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR EY 
               
               
                   
                   
                 LQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNV 
               
               
                   
                   
                 LVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSF 
               
               
                   
                   
                 GVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQ 
               
               
                   
                   
                 RPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEP 
               
               
                   
                   
                 LPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 AGCGCTCTTGCGGCCACAGGCGCGGCGTCCTCGGCGGCGGGCGGCAGCTAGCGGGAG 
               
               
                 NO: 5 
                 isoform 3 
                 CCGGGACGCCGGTGCAGCCGCAGCGCGCGGAGGAACCCGGGTGTGCCGGGAGCTGGG 
               
               
                   
                 Nucleic acid 
                 CGGCCACGTCCGGACGGGACCGAGACCCCTCGTAGCGCATTGCGGCGACCTCGCCTT 
               
               
                   
                 sequence 
                 CCCCGGCCGCGAGCGCGCCGCTGCTTGAAAAGCCGCGGAACCCAAGGACTTTTCTCC 
               
               
                   
                   
                 GGTCCGAGCTCGGGGCGCCCCGCAGGGCGCACGGTACCCGTGCTGCAGTCGGGCACG 
               
               
                   
                   
                 CCGCGGCGCCGGGGCCTCCGCAGGGCGATGGAGCCCGGTCTGCAAGGAAAGTGAGGC 
               
               
                   
                   
                 GCCGCCGCTGCGTTCTGGAGGAGGGGGGCACAAGGTCTGGAGACCCCGGGTGGCGGA 
               
               
                   
                   
                 CGGGAGCCCTCCCCCCGCCCCGCCTCCGGGGCACCAGCTCCGGCTCCATTGTTCCCG 
               
               
                   
                   
                 CCCGGGCTGGAGGCGCCGAGCACCGAGCGCCGCCGGGAGTCGAGCGCCGGCCGCGGA 
               
               
                   
                   
                 GCTCTTGCGACCCCGCCAGGACCCGAACAGAGCCCGGGGGCGGCGGGCCGGAGCCGG 
               
               
                   
                   
                 GGACGCGGGCACACGCCCGCTCGCACAAGCCACGGCGGACTCTCCCGAGGCGGAACC 
               
               
                   
                   
                 TCCACGCCGAGCGAGGGTCAGTTTGAAAAGGAGGATCGAGCTCACTGTGGAGTATCC 
               
               
                   
                   
                 ATGGAGATGTGGAGCCTTGTCACCAACCTCTAACTGCAGAACTGGGATGTGGAGCTG 
               
               
                   
                   
                 GAAGTGCCTCCTCTTCTGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCC 
               
               
                   
                   
                 GTCCCCGACCTTGCCTGAACAAGCCCAGCCCTGGGGAGCCCCTGTGGAAGTGGAGTC 
               
               
                   
                   
                 CTTCCTGGTCCACCCCGGTGACCTGCTGCAGCTTCGCTGTCGGCTGCGGGACGATGT 
               
               
                   
                   
                 GCAGAGCATCAACTGGCTGCGGGACGGGGTGCAGCTGGCGGAAAGCAACCGCACCCG 
               
               
                   
                   
                 CATCACAGGGGAGGAGGTGGAGGTGCAGGACTCCGTGCCCGCAGACTCCGGCCTCTA 
               
               
                   
                   
                 TGCTTGCGTAACCAGCAGCCCCTCGGGCAGTGACACCACCTACTTCTCCGTCAATGT 
               
               
                   
                   
                 TTCAGATGCTCTCCCCTCCTCGGAGGATGATGATGATGATGATGACTCCTCTTCAGA 
               
               
                   
                   
                 GGAGAAAGAAACAGATAACACCAAACCAAACCGTATGCCCGTAGCTCCATATTGGAC 
               
               
                   
                   
                 ATCCCCAGAAAAGATGGAAAAGAAATTGCATGCAGTGCCGGCTGCCAAGACAGTGAA 
               
               
                   
                   
                 GTTCAAATGCCCTTCCAGTGGGACCCCAAACCCCACACTGCGCTGGTTGAAAAATGG 
               
               
                   
                   
                 CAAAGAATTCAAACCTGACCACAGAATTGGAGGCTACAAGGTCCGTTATGCCACCTG 
               
               
                   
                   
                 GAGCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACTACACCTGCATTGT 
               
               
                   
                   
                 GGAGAATGAGTACGGCAGCATCAACCACACATACCAGCTGGATGTCGTGGAGCGGTC 
               
               
                   
                   
                 CCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGCCAACAAAACAGTGGCCCTGGG 
               
               
                   
                   
                 TAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGACCCGCAGCCGCACATCCAGTG 
               
               
                   
                   
                 GCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACAACCTGCCTTATGT 
               
               
                   
                   
                 CCAGATCTTGAAGACTGCTGGAGTTAATACCACCGACAAAGAGATGGAGGTGCTTCA 
               
               
                   
                   
                 CTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACGTGCTTGGCGGGTAACTC 
               
               
                   
                   
                 TATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAAGCCCTGGAAGAGAG 
               
               
                   
                   
                 GCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTATTGCACAGGGGC 
               
               
                   
                   
                 CTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGATGAAGAGTGGTAC 
               
               
                   
                   
                 CAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGGCCAAGAGCATCCC 
               
               
                   
                   
                 TCTGCGCAGACAGGTGTCTGCTGACTCCAGTGCATCCATGAACTCTGGGGTTCTTCT 
               
               
                   
                   
                 GGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCATGCTAGCAGGGGTCTCTGA 
               
               
                   
                   
                 GTATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTCGGGACAGACTGGTCTTAGG 
               
               
                   
                   
                 CAAACCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCT 
               
               
                   
                   
                 GGACAAGGACAAACCCAACCGTGTGACCAAAGTGGCTGTGAAGATGTTGAAGTCGGA 
               
               
                   
                   
                 CGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAATGGAGATGATGAAGATGAT 
               
               
                   
                   
                 CGGGAAGCATAAGAATATCATCAACCTGCTGGGGGCCTGCACGCAGGATGGTCCCTT 
               
               
                   
                   
                 GTATGTCATCGTGGAGTATGCCTCCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCG 
               
               
                   
                   
                 GAGGCCCCCAGGGCTGGAATACTGCTACAACCCCAGCCACAACCCAGAGGAGCAGCT 
               
               
                   
                   
                 CTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGGCCCGAGGCATGGAGTATCT 
               
               
                   
                   
                 GGCCTCCAAGAAGTGCATACACCGAGACCTGGCAGCCAGGAATGTCCTGGTGACAGA 
               
               
                   
                   
                 GGACAATGTGATGAAGATAGCAGACTTTGGCCTCGCACGGGACATTCACCACATCGA 
               
               
                   
                   
                 CTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGAAGTGGATGGCACCCGAGGC 
               
               
                   
                   
                 ATTATTTGACCGGATCTACACCCACCAGAGTGATGTGTGGTCTTTCGGGGTGCTCCT 
               
               
                   
                   
                 GTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCCGGTGTGCCTGTGGAGGAACT 
               
               
                   
                   
                 TTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGCCCAGTAACTGCACCAACGA 
               
               
                   
                   
                 GCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGCCCTCACAGAGACCCACCTT 
               
               
                   
                   
                 CAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTTGACCTCCAACCAGGAGTA 
               
               
                   
                   
                 CCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCAGCTTTCCCGACACCCGGAG 
               
               
                   
                   
                 CTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTCATGAGCCGCTGCCCGAGGA 
               
               
                   
                   
                 GCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATGGCGGACTCAAACGCCGCTG 
               
               
                   
                   
                 ACTGCCACCCACACGCCCTCCCCAGACTCCACCGTCAGCTGTAACCCTCACCCACAG 
               
               
                   
                   
                 CCCCTGCTGGGCCCACCACCTGTCCGTCCCTGTCCCCTTTCCTGCTGGCAGGAGCCG 
               
               
                   
                   
                 GCTGCCTACCAGGGGCCTTCCTGTGTGGCCTGCCTTCACCCCACTCAGCTCACCTCT 
               
               
                   
                   
                 CCCTCCACCTCCTCTCCACCTGCTGGTGAGAGGTGCAAAGAGGCAGATCTTTGCTGC 
               
               
                   
                   
                 CAGCCACTTCATCCCCTCCCAGATGTTGGACCAACACCCCTCCCTGCCACCAGGCAC 
               
               
                   
                   
                 TGCCTGGAGGGCAGGGAGTGGGAGCCAATGAACAGGCATGCAAGTGAGAGCTTCCTG 
               
               
                   
                   
                 AGCTTTCTCCTGTCGGTTTGGTCTGTTTTGCCTTCACCCATAAGCCCCTCGCACTCT 
               
               
                   
                   
                 GGTGGCAGGTGCCTTGTCCTCAGGGCTACAGCAGTAGGGAGGTCAGTGCTTCGTGCC 
               
               
                   
                   
                 TCGATTGAAGGTGACCTCTGCCCCAGATAGGTGGTGCCAGTGGCTTATTAATTCCGA 
               
               
                   
                   
                 TACTAGTTTGCTTTGCTGACCAAATGCCTGGTACCAGAGGATGGTGAGGCGAAGGCC 
               
               
                   
                   
                 AGGTTGGGGGCAGTGTTGTGGCCCTGGGGCCCAGCCCCAAACTGGGGGCTCTGTATA 
               
               
                   
                   
                 TAGCTATGAAGAAAACACAAAGTGTATAAATCTGAGTATATATTTACATGTCTTTTT 
               
               
                   
                   
                 AAAAGGGTCGTTACCAGAGATTTACCCATCGGGTAAGATGCTCCTGGTGGCTGGGAG 
               
               
                   
                   
                 GCATCAGTTGCTATATATTAAAAACAAAAAAGAAAAAAAAGGAAAATGTTTTTAAAA 
               
               
                   
                   
                 AGGTCATATATTTTTTGCTACTTTTGCTGTTTTATTTTTTTAAATTATGTTCTAAAC 
               
               
                   
                   
                 CTATTTTCAGTTTAGGTCCCTCAATAAAAATTGCTGCTGCTTCATTTATCTATGGGC 
               
               
                   
                   
                 TGTATGAAAAGGGTGGGAATGTCCACTGGAAAGAAGGGACACCCACGGGCCCTGGGG 
               
               
                   
                   
                 CTAGGTCTGTCCCGAGGGCACCGCATGCTCCCGGCGCAGGTTCCTTGTAACCTCTTC 
               
               
                   
                   
                 TTCCTAGGTCCTGCACCCAGACCTCACGACGCACCTCCTGCCTCTCCGCTGCTTTTG 
               
               
                   
                   
                 GAAAGTCAGAAAAAGAAGATGTCTGCTTCGAGGGCAGGAACCCCATCCATGCAGTAG 
               
               
                   
                   
                 AGGCGCTGGGCAGAGAGTCAAGGCCCAGCAGCCATCGACCATGGATGGTTTCCTCCA 
               
               
                   
                   
                 AGGAAACCGGTGGGGTTGGGCTGGGGAGGGGGCACCTACCTAGGAATAGCCACGGGG 
               
               
                   
                   
                 TAGAGCTACAGTGATTAAGAGGAAAGCAAGGGCGCGGTTGCTCACGCCTGTAATCCC 
               
               
                   
                   
                 AGCACTTTGGGACACCGAGGTGGGCAGATCACTTCAGGTCAGGAGTTTGAGACCAGC 
               
               
                   
                   
                 CTGGCCAACTTAGTGAAACCCCATCTCTACTAAAAATGCAAAAATTATCCAGGCATG 
               
               
                   
                   
                 GTGGCACACGCCTGTAATCCCAGCTCCACAGGAGGCTGAGGCAGAATCCCTTGAAGC 
               
               
                   
                   
                 TGGGAGGCGGAGGTTGCAGTGAGCCGAGATTGCGCCATTGCACTCCAGCCTGGGCAA 
               
               
                   
                   
                 CAGAGAAAACAAAAAGGAAAACAAATGATGAAGGTCTGCAGAAACTGAAACCCAGAC 
               
               
                   
                   
                 ATGTGTCTGCCCCCTCTATGTGGGCATGGTTTTGCCAGTGCTTCTAAGTGCAGGAGA 
               
               
                   
                   
                 ACATGTCACCTGAGGCTAGTTTTGCATTCAGGTCCCTGGCTTCGTTTCTTGTTGGTA 
               
               
                   
                   
                 TGCCTCCCCAGATCGTCCTTCCTGTATCCATGTGACCAGACTGTATTTGTTGGGACT 
               
               
                   
                   
                 GTCGCAGATCTTGGCTTCTTACAGTTCTTCCTGTCCAAACTCCATCCTGTCCCTCAG 
               
               
                   
                   
                 GAACGGGGGGAAAATTCTCCGAATGTTTTTGGTTTTTTGGCTGCTTGGAATTTACTT 
               
               
                   
                   
                 CTGCCACCTGCTGGTCATCACTGTCCTCACTAAGTGGATTCTGGCTCCCCCGTACCT 
               
               
                   
                   
                 CATGGCTCAAACTACCACTCCTCAGTCGCTATATTAAAGCTTATATTTTGCTGGATT 
               
               
                   
                   
                 ACTGCTAAATACAAAAGAAAGTTCAATATGTTTTCATTTCTGTAGGGAAAATGGGAT 
               
               
                   
                   
                 TGCTGCTTTAAATTTCTGAGCTAGGGATTTTTTGGCAGCTGCAGTGTTGGCGACTAT 
               
               
                   
                   
                 TGTAAAATTCTCTTTGTTTCTCTCTGTAAATAGCACCTGCTAACATTACAATTTGTA 
               
               
                   
                   
                 TTTATGTTTAAAGAAGGCATCATTTGGTGAACAGAACTAGGAAATGAATTTTTAGCT 
               
               
                   
                   
                 CTTAAAAGCATTTGCTTTGAGACCGCACAGGAGTGTCTTTCCTTGTAAAACAGTGAT 
               
               
                   
                   
                 GATAATTTCTGCCTTGGCCCTACCTTGAAGCAATGTTGTGTGAAGGGATGAAGAATC 
               
               
                   
                   
                 TAAAAGTCTTCATAAGTCCTTGGGAGAGGTGCTAGAAAAATATAAGGCACTATCATA 
               
               
                   
                   
                 ATTA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRL 
               
               
                 NO: 6 
                 isoform 3 
                 RDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYF 
               
               
                   
                 Amino acid 
                 SVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAA 
               
               
                   
                 sequence 
                 KTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNY 
               
               
                   
                   
                 TCIVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQP 
               
               
                   
                   
                 HIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCL 
               
               
                   
                   
                 AGNSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKM 
               
               
                   
                   
                 KSGTKKSDFHSQMAVHKLAKSIPLRRQVSADSSASMNSGVLLVRPSRLSSSGTPMLA 
               
               
                   
                   
                 GVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKM 
               
               
                   
                   
                 LKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR EY 
               
               
                   
                   
                 LQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNV 
               
               
                   
                   
                 LVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSF 
               
               
                   
                   
                 GVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQ 
               
               
                   
                   
                 RPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEP 
               
               
                   
                   
                 LPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 CCCTTTCACCTCCTGGCTCCCTCCCGGGCGATCCGCGCCCCTTGGGTCTCCCCTCCC 
               
               
                 NO: 7 
                 isoform 4 
                 TTCCCTCCGTCCGCGTCTCCTGCGCCCCCTCCCTGCGCTCGTCCCGCCGCTCTTCCC 
               
               
                   
                 Nucleic acid 
                 GCCGCCCAACTTTTCCTCCAACTCGCGCTCGGGAGCTGGCGAGGCGGCGGCGGCTCC 
               
               
                   
                 sequence 
                 TCAAAGTGGGAGAGCTTCAAGGTCACGTGGTCCGTCCAGCCCCTGCTATCTCACCAG 
               
               
                   
                   
                 ACACTGTCCACCCTGTATGTTGGATCAGTACTCCAGTGAGAAGACAGCAGGCACTTT 
               
               
                   
                   
                 CACCCATGCAGCCCATTCAGTCTTCATAACCACCTGTGATGGAGGCAAGGGTCAGTT 
               
               
                   
                   
                 TGAAAAGGAGGATCGAGCTCACTGTGGAGTATCCATGGAGATGTGGAGCCTTGTCAC 
               
               
                   
                   
                 CAACCTCTAACTGCAGAACTGGGATGTGGAGCTGGAAGTGCCTCCTCTTCTGGGCTG 
               
               
                   
                   
                 TGCTGGTCACAGCCACACTCTGCACCGCTAGGCCGTCCCCGACCTTGCCTGAACAAG 
               
               
                   
                   
                 CCCAGCCCTGGGGAGCCCCTGTGGAAGTGGAGTCCTTCCTGGTCCACCCCGGTGACC 
               
               
                   
                   
                 TGCTGCAGCTTCGCTGTCGGCTGCGGGACGATGTGCAGAGCATCAACTGGCTGCGGG 
               
               
                   
                   
                 ACGGGGTGCAGCTGGCGGAAAGCAACCGCACCCGCATCACAGGGGAGGAGGTGGAGG 
               
               
                   
                   
                 TGCAGGACTCCGTGCCCGCAGACTCCGGCCTCTATGCTTGCGTAACCAGCAGCCCCT 
               
               
                   
                   
                 CGGGCAGTGACACCACCTACTTCTCCGTCAATGTTTCAGATGCTCTCCCCTCCTCGG 
               
               
                   
                   
                 AGGATGATGATGATGATGATGACTCCTCTTCAGAGGAGAAAGAAACAGATAACACCA 
               
               
                   
                   
                 AACCAAACCCCGTAGCTCCATATTGGACATCCCCAGAAAAGATGGAAAAGAAATTGC 
               
               
                   
                   
                 ATGCAGTGCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACCCCAA 
               
               
                   
                   
                 ACCCCACACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAACCTGACCACAGAATTG 
               
               
                   
                   
                 GAGGCTACAAGGTCCGTTATGCCACCTGGAGCATCATAATGGACTCTGTGGTGCCCT 
               
               
                   
                   
                 CTGACAAGGGCAACTACACCTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACA 
               
               
                   
                   
                 CATACCAGCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGT 
               
               
                   
                   
                 TGCCCGCCAACAAAACAGTGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGT 
               
               
                   
                   
                 ACAGTGACCCGCAGCCGCACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCA 
               
               
                   
                   
                 AGATTGGCCCAGACAACCTGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATA 
               
               
                   
                   
                 CCACCGACAAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAG 
               
               
                   
                   
                 GGGAGTATACGTGCTTGGCGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGT 
               
               
                   
                   
                 TGACCGTTCTGGAAGCCCTGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACC 
               
               
                   
                   
                 TGGAGATCATCATCTATTGCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGG 
               
               
                   
                   
                 TCATCGTCTACAAGATGAAGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGG 
               
               
                   
                   
                 CTGTGCACAAGCTGGCCAAGAGCATCCCTCTGCGCAGACAGGTAACAGTGTCTGCTG 
               
               
                   
                   
                 ACTCCAGTGCATCCATGAACTCTGGGGTTCTTCTGGTTCGGCCATCACGGCTCTCCT 
               
               
                   
                   
                 CCAGTGGGACTCCCATGCTAGCAGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTC 
               
               
                   
                   
                 GCTGGGAGCTGCCTCGGGACAGACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCT 
               
               
                   
                   
                 TTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAGGACAAACCCAACCGTG 
               
               
                   
                   
                 TGACCAAAGTGGCTGTGAAGATGTTGAAGTCGGACGCAACAGAGAAAGACTTGTCAG 
               
               
                   
                   
                 ACCTGATCTCAGAAATGGAGATGATGAAGATGATCGGGAAGCATAAGAATATCATCA 
               
               
                   
                   
                 ACCTGCTGGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATCGTGGAGTATGCCT 
               
               
                   
                   
                 CCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCCCCAGGGCTGGAATACT 
               
               
                   
                   
                 GCTACAACCCCAGCCACAACCCAGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCT 
               
               
                   
                   
                 GCGCCTACCAGGTGGCCCGAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACC 
               
               
                   
                   
                 GAGACCTGGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTGATGAAGATAGCAG 
               
               
                   
                   
                 ACTTTGGCCTCGCACGGGACATTCACCACATCGACTACTATAAAAAGACAACCAACG 
               
               
                   
                   
                 GCCGACTGCCTGTGAAGTGGATGGCACCCGAGGCATTATTTGACCGGATCTACACCC 
               
               
                   
                   
                 ACCAGAGTGATGTGTGGTCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCG 
               
               
                   
                   
                 GCTCCCCATACCCCGGTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTC 
               
               
                   
                   
                 ACCGCATGGACAAGCCCAGTAACTGCACCAACGAGCTGTACATGATGATGCGGGACT 
               
               
                   
                   
                 GCTGGCATGCAGTGCCCTCACAGAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGG 
               
               
                   
                   
                 ACCGCATCGTGGCCTTGACCTCCAACCAGGAGTACCTGGACCTGTCCATGCCCCTGG 
               
               
                   
                   
                 ACCAGTACTCCCCCAGCTTTCCCGACACCCGGAGCTCTACGTGCTCCTCAGGGGAGG 
               
               
                   
                   
                 ATTCCGTCTTCTCTCATGAGCCGCTGCCCGAGGAGCCCTGCCTGCCCCGACACCCAG 
               
               
                   
                   
                 CCCAGCTTGCCAATGGCGGACTCAAACGCCGCTGACTGCCACCCACACGCCCTCCCC 
               
               
                   
                   
                 AGACTCCACCGTCAGCTGTAACCCTCACCCACAGCCCCTGCTGGGCCCACCACCTGT 
               
               
                   
                   
                 CCGTCCCTGTCCCCTTTCCTGCTGGCAGGAGCCGGCTGCCTACCAGGGGCCTTCCTG 
               
               
                   
                   
                 TGTGGCCTGCCTTCACCCCACTCAGCTCACCTCTCCCTCCACCTCCTCTCCACCTGC 
               
               
                   
                   
                 TGGTGAGAGGTGCAAAGAGGCAGATCTTTGCTGCCAGCCACTTCATCCCCTCCCAGA 
               
               
                   
                   
                 TGTTGGACCAACACCCCTCCCTGCCACCAGGCACTGCCTGGAGGGCAGGGAGTGGGA 
               
               
                   
                   
                 GCCAATGAACAGGCATGCAAGTGAGAGCTTCCTGAGCTTTCTCCTGTCGGTTTGGTC 
               
               
                   
                   
                 TGTTTTGCCTTCACCCATAAGCCCCTCGCACTCTGGTGGCAGGTGCCTTGTCCTCAG 
               
               
                   
                   
                 GGCTACAGCAGTAGGGAGGTCAGTGCTTCGTGCCTCGATTGAAGGTGACCTCTGCCC 
               
               
                   
                   
                 CAGATAGGTGGTGCCAGTGGCTTATTAATTCCGATACTAGTTTGCTTTGCTGACCAA 
               
               
                   
                   
                 ATGCCTGGTACCAGAGGATGGTGAGGCGAAGGCCAGGTTGGGGGCAGTGTTGTGGCC 
               
               
                   
                   
                 CTGGGGCCCAGCCCCAAACTGGGGGCTCTGTATATAGCTATGAAGAAAACACAAAGT 
               
               
                   
                   
                 GTATAAATCTGAGTATATATTTACATGTCTTTTTAAAAGGGTCGTTACCAGAGATTT 
               
               
                   
                   
                 ACCCATCGGGTAAGATGCTCCTGGTGGCTGGGAGGCATCAGTTGCTATATATTAAAA 
               
               
                   
                   
                 ACAAAAAAGAAAAAAAAGGAAAATGTTTTTAAAAAGGTCATATATTTTTTGCTACTT 
               
               
                   
                   
                 TTGCTGTTTTATTTTTTTAAATTATGTTCTAAACCTATTTTCAGTTTAGGTCCCTCA 
               
               
                   
                   
                 ATAAAAATTGCTGCTGCTTCATTTATCTATGGGCTGTATGAAAAGGGTGGGAATGTC 
               
               
                   
                   
                 CACTGGAAAGAAGGGACACCCACGGGCCCTGGGGCTAGGTCTGTCCCGAGGGCACCG 
               
               
                   
                   
                 CATGCTCCCGGCGCAGGTTCCTTGTAACCTCTTCTTCCTAGGTCCTGCACCCAGACC 
               
               
                   
                   
                 TCACGACGCACCTCCTGCCTCTCCGCTGCTTTTGGAAAGTCAGAAAAAGAAGATGTC 
               
               
                   
                   
                 TGCTTCGAGGGCAGGAACCCCATCCATGCAGTAGAGGCGCTGGGCAGAGAGTCAAGG 
               
               
                   
                   
                 CCCAGCAGCCATCGACCATGGATGGTTTCCTCCAAGGAAACCGGTGGGGTTGGGCTG 
               
               
                   
                   
                 GGGAGGGGGCACCTACCTAGGAATAGCCACGGGGTAGAGCTACAGTGATTAAGAGGA 
               
               
                   
                   
                 AAGCAAGGGCGCGGTTGCTCACGCCTGTAATCCCAGCACTTTGGGACACCGAGGTGG 
               
               
                   
                   
                 GCAGATCACTTCAGGTCAGGAGTTTGAGACCAGCCTGGCCAACTTAGTGAAACCCCA 
               
               
                   
                   
                 TCTCTACTAAAAATGCAAAAATTATCCAGGCATGGTGGCACACGCCTGTAATCCCAG 
               
               
                   
                   
                 CTCCACAGGAGGCTGAGGCAGAATCCCTTGAAGCTGGGAGGCGGAGGTTGCAGTGAG 
               
               
                   
                   
                 CCGAGATTGCGCCATTGCACTCCAGCCTGGGCAACAGAGAAAACAAAAAGGAAAACA 
               
               
                   
                   
                 AATGATGAAGGTCTGCAGAAACTGAAACCCAGACATGTGTCTGCCCCCTCTATGTGG 
               
               
                   
                   
                 GCATGGTTTTGCCAGTGCTTCTAAGTGCAGGAGAACATGTCACCTGAGGCTAGTTTT 
               
               
                   
                   
                 GCATTCAGGTCCCTGGCTTCGTTTCTTGTTGGTATGCCTCCCCAGATCGTCCTTCCT 
               
               
                   
                   
                 GTATCCATGTGACCAGACTGTATTTGTTGGGACTGTCGCAGATCTTGGCTTCTTACA 
               
               
                   
                   
                 GTTCTTCCTGTCCAAACTCCATCCTGTCCCTCAGGAACGGGGGGAAAATTCTCCGAA 
               
               
                   
                   
                 TGTTTTTGGTTTTTTGGCTGCTTGGAATTTACTTCTGCCACCTGCTGGTCATCACTG 
               
               
                   
                   
                 TCCTCACTAAGTGGATTCTGGCTCCCCCGTACCTCATGGCTCAAACTACCACTCCTC 
               
               
                   
                   
                 AGTCGCTATATTAAAGCTTATATTTTGCTGGATTACTGCTAAATACAAAAGAAAGTT 
               
               
                   
                   
                 CAATATGTTTTCATTTCTGTAGGGAAAATGGGATTGCTGCTTTAAATTTCTGAGCTA 
               
               
                   
                   
                 GGGATTTTTTGGCAGCTGCAGTGTTGGCGACTATTGTAAAATTCTCTTTGTTTCTCT 
               
               
                   
                   
                 CTGTAAATAGCACCTGCTAACATTACAATTTGTATTTATGTTTAAAGAAGGCATCAT 
               
               
                   
                   
                 TTGGTGAACAGAACTAGGAAATGAATTTTTAGCTCTTAAAAGCATTTGCTTTGAGAC 
               
               
                   
                   
                 CGCACAGGAGTGTCTTTCCTTGTAAAACAGTGATGATAATTTCTGCCTTGGCCCTAC 
               
               
                   
                   
                 CTTGAAGCAATGTTGTGTGAAGGGATGAAGAATCTAAAAGTCTTCATAAGTCCTTGG 
               
               
                   
                   
                 GAGAGGTGCTAGAAAAATATAAGGCACTATCATAATTACAGTGATGTCCTTGCTGTT 
               
               
                   
                   
                 ACTACTCAAATCACCCACAAATTTCCCCAAAGACTGCGCTAGCTGTCAAATAAAAGA 
               
               
                   
                   
                 CAGTGAAATTGACCTGA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MEARVSLKRRIELTVEYPWRCGALSPTSNCRTGMWSWKCLLFWAVLVTATLCTARPS 
               
               
                 NO: 8 
                 isoform 4 
                 PTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSINWLRDGVQLAESNRTRI 
               
               
                   
                 Amino acid 
                 TGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDALPSSEDDDDDDDSSSEE 
               
               
                   
                 sequence 
                 KETDNTKPNPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLRWLKNGKEF 
               
               
                   
                   
                 KPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSINHTYQLDVVERSPHR 
               
               
                   
                   
                 PILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKIGPDNLPYVQIL 
               
               
                   
                   
                 KTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAV 
               
               
                   
                   
                 MTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKSIPLRR 
               
               
                   
                   
                 QVTVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVLGK 
               
               
                   
                   
                 PLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIG 
               
               
                   
                   
                 KHKNIINLLGACTQDGPLYV IVEYASKGNLR EYLQARRPPGLEYCYNPSHNPEEQLS 
               
               
                   
                   
                 SKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDY 
               
               
                   
                   
                 YKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELF 
               
               
                   
                   
                 KLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYL 
               
               
                   
                   
                 DLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 GCGCTCTTGCGGCCACAGGCGCGGCGTCCTCGGCGGCGGGCGGCAGCTAGCGGGAGC 
               
               
                 NO: 9 
                 isoform 5 
                 CGGGACGCCGGTGCAGCCGCAGCGCGCGGAGGAACCCGGGTGTGCCGGGAGCTGGGC 
               
               
                   
                 Nucleic acid 
                 GGCCACGTCCGGACGGGACCGAGACCCCTCGTAGCGCATTGCGGCGACCTCGCCTTC 
               
               
                   
                 sequence 
                 CCCGGCCGCGAGCGCGCCGCTGCTTGAAAAGCCGCGGAACCCAAGGACTTTTCTCCG 
               
               
                   
                   
                 GTCCGAGCTCGGGGCGCCCCGCAGGGCGCACGGTACCCGTGCTGCAGTCGGGCACGC 
               
               
                   
                   
                 CGCGGCGCCGGGGCCTCCGCAGGGCGATGGAGCCCGGTCTGCAAGGAAAGTGAGGCG 
               
               
                   
                   
                 CCGCCGCTGCGTTCTGGAGGAGGGGGGCACAAGGTCTGGAGACCCCGGGTGGCGGAC 
               
               
                   
                   
                 GGGAGCCCTCCCCCCGCCCCGCCTCCGGGGCACCAGCTCCGGCTCCATTGTTCCCGC 
               
               
                   
                   
                 CCGGGCTGGAGGCGCCGAGCACCGAGCGCCGCCGGGAGTCGAGCGCCGGCCGCGGAG 
               
               
                   
                   
                 CTCTTGCGACCCCGCCAGGACCCGAACAGAGCCCGGGGGCGGCGGGCCGGAGCCGGG 
               
               
                   
                   
                 GACGCGGGCACACGCCCGCTCGCACAAGCCACGGCGGACTCTCCCGAGGCGGAACCT 
               
               
                   
                   
                 CCACGCCGAGCGAGGGTCAGTTTGAAAAGGAGGATCGAGCTCACTGTGGAGTATCCA 
               
               
                   
                   
                 TGGAGATGTGGAGCCTTGTCACCAACCTCTAACTGCAGAACTGGGATGTGGAGCTGG 
               
               
                   
                   
                 AAGTGCCTCCTCTTCTGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCCG 
               
               
                   
                   
                 TCCCCGACCTTGCCTGAACAAGGATGGCAGCTGTGACCCGGGATTTCGGTGAGATGC 
               
               
                   
                   
                 TTCTGCACTCTGGCCGGGTCCTGCCAGCCGAAGCCCAGCCCTGGGGAGCCCCTGTGG 
               
               
                   
                   
                 AAGTGGAGTCCTTCCTGGTCCACCCCGGTGACCTGCTGCAGCTTCGCTGTCGGCTGC 
               
               
                   
                   
                 GGGACGATGTGCAGAGCATCAACTGGCTGCGGGACGGGGTGCAGCTGGCGGAAAGCA 
               
               
                   
                   
                 ACCGCACCCGCATCACAGGGGAGGAGGTGGAGGTGCAGGACTCCGTGCCCGCAGACT 
               
               
                   
                   
                 CCGGCCTCTATGCTTGCGTAACCAGCAGCCCCTCGGGCAGTGACACCACCTACTTCT 
               
               
                   
                   
                 CCGTCAATGTTTCAGATGCTCTCCCCTCCTCGGAGGATGATGATGATGATGATGACT 
               
               
                   
                   
                 CCTCTTCAGAGGAGAAAGAAACAGATAACACCAAACCAAACCGTATGCCCGTAGCTC 
               
               
                   
                   
                 CATATTGGACATCCCCAGAAAAGATGGAAAAGAAATTGCATGCAGTGCCGGCTGCCA 
               
               
                   
                   
                 AGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACCCCAAACCCCACACTGCGCTGGT 
               
               
                   
                   
                 TGAAAAATGGCAAAGAATTCAAACCTGACCACAGAATTGGAGGCTACAAGGTCCGTT 
               
               
                   
                   
                 ATGCCACCTGGAGCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACTACA 
               
               
                   
                   
                 CCTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCAGCTGGATGTCG 
               
               
                   
                   
                 TGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGCCAACAAAACAG 
               
               
                   
                   
                 TGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGACCCGCAGCCGC 
               
               
                   
                   
                 ACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACAACC 
               
               
                   
                   
                 TGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGACAAAGAGATGG 
               
               
                   
                   
                 AGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACGTGCTTGG 
               
               
                   
                   
                 CGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAAGCCC 
               
               
                   
                   
                 TGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTATT 
               
               
                   
                   
                 GCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGATGA 
               
               
                   
                   
                 AGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGGCCA 
               
               
                   
                   
                 AGAGCATCCCTCTGCGCAGACAGGTGTCTGCTGACTCCAGTGCATCCATGAACTCTG 
               
               
                   
                   
                 GGGTTCTTCTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCATGCTAGCAG 
               
               
                   
                   
                 GGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTCGGGACAGAC 
               
               
                   
                   
                 TGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGTTGGCAGAGG 
               
               
                   
                   
                 CTATCGGGCTGGACAAGGACAAACCCAACCGTGTGACCAAAGTGGCTGTGAAGATGT 
               
               
                   
                   
                 TGAAGTCGGACGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAATGGAGATGA 
               
               
                   
                   
                 TGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCTGGGGGCCTGCACGCAGG 
               
               
                   
                   
                 ATGGTCCCTTGTATGTCATCGTGGAGTATGCCTCCAAGGGCAACCTGCGGGAGTACC 
               
               
                   
                   
                 TGCAGGCCCGGAGGCCCCCAGGGCTGGAATACTGCTACAACCCCAGCCACAACCCAG 
               
               
                   
                   
                 AGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGGCCCGAGGCA 
               
               
                   
                   
                 TGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACCTGGCAGCCAGGAATGTCC 
               
               
                   
                   
                 TGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTTGGCCTCGCACGGGACATTC 
               
               
                   
                   
                 ACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGAAGTGGATGG 
               
               
                   
                   
                 CACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGATGTGTGGTCTTTCG 
               
               
                   
                   
                 GGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCCGGTGTGCCTG 
               
               
                   
                   
                 TGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGCCCAGTAACT 
               
               
                   
                   
                 GCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGCCCTCACAGA 
               
               
                   
                   
                 GACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTTGACCTCCA 
               
               
                   
                   
                 ACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCAGCTTTCCCG 
               
               
                   
                   
                 ACACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTCATGAGCCGC 
               
               
                   
                   
                 TGCCCGAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATGGCGGACTCA 
               
               
                   
                   
                 AACGCCGCTGACTGCCACCCACACGCCCTCCCCAGACTCCACCGTCAGCTGTAACCC 
               
               
                   
                   
                 TCACCCACAGCCCCTGCTGGGCCCACCACCTGTCCGTCCCTGTCCCCTTTCCTGCTG 
               
               
                   
                   
                 GCAGGAGCCGGCTGCCTACCAGGGGCCTTCCTGTGTGGCCTGCCTTCACCCCACTCA 
               
               
                   
                   
                 GCTCACCTCTCCCTCCACCTCCTCTCCACCTGCTGGTGAGAGGTGCAAAGAGGCAGA 
               
               
                   
                   
                 TCTTTGCTGCCAGCCACTTCATCCCCTCCCAGATGTTGGACCAACACCCCTCCCTGC 
               
               
                   
                   
                 CACCAGGCACTGCCTGGAGGGCAGGGAGTGGGAGCCAATGAACAGGCATGCAAGTGA 
               
               
                   
                   
                 GAGCTTCCTGAGCTTTCTCCTGTCGGTTTGGTCTGTTTTGCCTTCACCCATAAGCCC 
               
               
                   
                   
                 CTCGCACTCTGGTGGCAGGTGCCTTGTCCTCAGGGCTACAGCAGTAGGGAGGTCAGT 
               
               
                   
                   
                 GCTTCGTGCCTCGATTGAAGGTGACCTCTGCCCCAGATAGGTGGTGCCAGTGGCTTA 
               
               
                   
                   
                 TTAATTCCGATACTAGTTTGCTTTGCTGACCAAATGCCTGGTACCAGAGGATGGTGA 
               
               
                   
                   
                 GGCGAAGGCCAGGTTGGGGGCAGTGTTGTGGCCCTGGGGCCCAGCCCCAAACTGGGG 
               
               
                   
                   
                 GCTCTGTATATAGCTATGAAGAAAACACAAAGTGTATAAATCTGAGTATATATTTAC 
               
               
                   
                   
                 ATGTCTTTTTAAAAGGGTCGTTACCAGAGATTTACCCATCGGGTAAGATGCTCCTGG 
               
               
                   
                   
                 TGGCTGGGAGGCATCAGTTGCTATATATTAAAAACAAAAAAGAAAAAAAAGGAAAAT 
               
               
                   
                   
                 GTTTTTAAAAAGGTCATATATTTTTTGCTACTTTTGCTGTTTTATTTTTTTAAATTA 
               
               
                   
                   
                 TGTTCTAAACCTATTTTCAGTTTAGGTCCCTCAATAAAAATTGCTGCTGCTTC 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MAAVTRDFGEMLLHSGRVLPAEAQPWGAPVEVESFLVHPGDLLQLRCRLRDDVQSIN 
               
               
                 NO: 10 
                 isoform 5 
                 WLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYFSVNVSDAL 
               
               
                   
                 Amino acid 
                 PSSEDDDDDDDSSSEEKETDNTKPNRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCP 
               
               
                   
                 sequence 
                 SSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTCIVENEY 
               
               
                   
                   
                 GSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHIQWLKHI 
               
               
                   
                   
                 EVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLS 
               
               
                   
                   
                 HHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSD 
               
               
                   
                   
                 FHSQMAVHKLAKSIPLRRQVSADSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELP 
               
               
                   
                   
                 EDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEK 
               
               
                   
                   
                 DLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR EYLQARRPPG 
               
               
                   
                   
                 LEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVM 
               
               
                   
                   
                 KIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIF 
               
               
                   
                   
                 TLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMNMRDCWHAVPSQRPTFKQLV 
               
               
                   
                   
                 EDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLP 
               
               
                   
                   
                 RHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 CTTGCGGCCACAGGCGCGGCGTCCTCGGCGGCGGGCGGCAGCTAGCGGGAGCCGGGA 
               
               
                 NO: 11 
                 isoform 6 
                 CGCCGGTGCAGCCGCAGCGCGCGGAGGAACCCGGGTGTGCCGGGAGCTGGGCGGCCA 
               
               
                   
                 Nucleic acid 
                 CGTCCGGACGGGACCGAGACCCCTCGTAGCGCATTGCGGCGACCTCGCCTTCCCCGG 
               
               
                   
                 sequence 
                 CCGCGAGCGCGCCGCTGCTTGAAAAGCCGCGGAACCCAAGGACTTTTCTCCGGTCCG 
               
               
                   
                   
                 AGCTCGGGGCGCCCCGCAGGGCGCACGGTACCCGTGCTGCAGTCGGGCACGCCGCGG 
               
               
                   
                   
                 CGCCGGGGCCTCCGCAGGGCGATGGAGCCCGGTCTGCAAGGAAAGTGAGGCGCCGCC 
               
               
                   
                   
                 GCTGCGTTCTGGAGGAGGGGGGCACAAGGTCTGGAGACCCCGGGTGGCGGACGGGAG 
               
               
                   
                   
                 CCCTCCCCCCGCCCCGCCTCCGGGGCACCAGCTCCGGCTCCATTGTTCCCGCCCGGG 
               
               
                   
                   
                 CTGGAGGCGCCGAGCACCGAGCGCCGCCGGGAGTCGAGCGCCGGCCGCGGAGCTCTT 
               
               
                   
                   
                 GCGACCCCGCCAGGACCCGAACAGAGCCCGGGGGCGGCGGGCCGGAGCCGGGGACGC 
               
               
                   
                   
                 GGGCACACGCCCGCTCGCACAAGCCACGGCGGACTCTCCCGAGGCGGAACCTCCACG 
               
               
                   
                   
                 CCGAGCGAGGGTCAGTTTGAAAAGGAGGATCGAGCTCACTGTGGAGTATCCATGGAG 
               
               
                   
                   
                 ATGTGGAGCCTTGTCACCAACCTCTAACTGCAGAACTGGGATGTGGAGCTGGAAGTG 
               
               
                   
                   
                 CCTCCTCTTCTGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCCGTCCCC 
               
               
                   
                   
                 GACCTTGCCTGAACAAGATGCTCTCCCCTCCTCGGAGGATGATGATGATGATGATGA 
               
               
                   
                   
                 CTCCTCTTCAGAGGAGAAAGAAACAGATAACACCAAACCAAACCGTATGCCCGTAGC 
               
               
                   
                   
                 TCCATATTGGACATCCCCAGAAAAGATGGAAAAGAAATTGCATGCAGTGCCGGCTGC 
               
               
                   
                   
                 CAAGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACCCCAAACCCCACACTGCGCTG 
               
               
                   
                   
                 GTTGAAAAATGGCAAAGAATTCAAACCTGACCACAGAATTGGAGGCTACAAGGTCCG 
               
               
                   
                   
                 TTATGCCACCTGGAGCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACTA 
               
               
                   
                   
                 CACCTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCAGCTGGATGT 
               
               
                   
                   
                 CGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGCCAACAAAAC 
               
               
                   
                   
                 AGTGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGACCCGCAGCC 
               
               
                   
                   
                 GCACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACAA 
               
               
                   
                   
                 CCTGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGACAAAGAGAT 
               
               
                   
                   
                 GGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACGTGCTT 
               
               
                   
                   
                 GGCGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAAGC 
               
               
                   
                   
                 CCTGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTA 
               
               
                   
                   
                 TTGCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGAT 
               
               
                   
                   
                 GAAGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGGC 
               
               
                   
                   
                 CAAGAGCATCCCTCTGCGCAGACAGGTAACAGTGTCTGCTGACTCCAGTGCATCCAT 
               
               
                   
                   
                 GAACTCTGGGGTTCTTCTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCAT 
               
               
                   
                   
                 GCTAGCAGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTCG 
               
               
                   
                   
                 GGACAGACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGTT 
               
               
                   
                   
                 GGCAGAGGCTATCGGGCTGGACAAGGACAAACCCAACCGTGTGACCAAAGTGGCTGT 
               
               
                   
                   
                 GAAGATGTTGAAGTCGGACGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAAT 
               
               
                   
                   
                 GGAGATGATGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCTGGGGGCCTG 
               
               
                   
                   
                 CACGCAGGATGGTCCCTTGTATGTCATCGTGGAGTATGCCTCCAAGGGCAACCTGCG 
               
               
                   
                   
                 GGAGTACCTGCAGGCCCGGAGGCCCCCAGGGCTGGAATACTGCTACAACCCCAGCCA 
               
               
                   
                   
                 CAACCCAGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGGC 
               
               
                   
                   
                 CCGAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACCTGGCAGCCAG 
               
               
                   
                   
                 GAATGTCCTGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTTGGCCTCGCACG 
               
               
                   
                   
                 GGACATTCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGAA 
               
               
                   
                   
                 GTGGATGGCACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGATGTGTG 
               
               
                   
                   
                 GTCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCCGG 
               
               
                   
                   
                 TGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGCC 
               
               
                   
                   
                 CAGTAACTGCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGCC 
               
               
                   
                   
                 CTCACAGAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTT 
               
               
                   
                   
                 GACCTCCAACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCAG 
               
               
                   
                   
                 CTTTCCCGACACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTCA 
               
               
                   
                   
                 TGAGCCGCTGCCCGAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATGG 
               
               
                   
                   
                 CGGACTCAAACGCCGCTGACTGCCACCCACACGCCCTCCCCAGACTCCACCGTCAGC 
               
               
                   
                   
                 TGTAACCCTCACCCACAGCCCCTGCTGGGCCCACCACCTGTCCGTCCCTGTCCCCTT 
               
               
                   
                   
                 TCCTGCTGGCAGGAGCCGGCTGCCTACCAGGGGCCTTCCTGTGTGGCCTGCCTTCAC 
               
               
                   
                   
                 CCCACTCAGCTCACCTCTCCCTCCACCTCCTCTCCACCTGCTGGTGAGAGGTGCAAA 
               
               
                   
                   
                 GAGGCAGATCTTTGCTGCCAGCCACTTCATCCCCTCCCAGATGTTGGACCAACACCC 
               
               
                   
                   
                 CTCCCTGCCACCAGGCACTGCCTGGAGGGCAGGGAGTGGGAGCCAATGAACAGGCAT 
               
               
                   
                   
                 GCAAGTGAGAGCTTCCTGAGCTTTCTCCTGTCGGTTTGGTCTGTTTTGCCTTCACCC 
               
               
                   
                   
                 ATAAGCCCCTCGCACTCTGGTGGCAGGTGCCTTGTCCTCAGGGCTACAGCAGTAGGG 
               
               
                   
                   
                 AGGTCAGTGCTTCGTGCCTCGATTGAAGGTGACCTCTGCCCCAGATAGGTGGTGCCA 
               
               
                   
                   
                 GTGGCTTATTAATTCCGATACTAGTTTGCTTTGCTGACCAAATGCCTGGTACCAGAG 
               
               
                   
                   
                 GATGGTGAGGCGAAGGCCAGGTTGGGGGCAGTGTTGTGGCCCTGGGGCCCAGCCCCA 
               
               
                   
                   
                 AACTGGGGGCTCTGTATATAGCTATGAAGAAAACACAAAGTGTATAAATCTGAGTAT 
               
               
                   
                   
                 ATATTTACATGTCTTTTTAAAAGGGTCGTTACCAGAGATTTACCCATCGGGTAAGAT 
               
               
                   
                   
                 GCTCCTGGTGGCTGGGAGGCATCAGTTGCTATATATTAAAAACAAAAAAGAAAAAAA 
               
               
                   
                   
                 AGGAAAATGTTTTTAAAAAGGTCATATATTTTTTGCTACTTTTGCTGTTTTATTTTT 
               
               
                   
                   
                 TTAAATTATGTTCTAAACCTATTTTCAGTTTAGGTCCCTCAATAAAAATTGCTGCTG 
               
               
                   
                   
                 CTTCA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQDALPSSEDDDDDDDSSSEEKETDNTKP 
               
               
                 NO: 12 
                 isoform 6 
                 NRMPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRI 
               
               
                   
                 Amino acid 
                 GGYKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSINHTYQLDVVERSPHRPILQAG 
               
               
                   
                 sequence 
                 LPANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVN 
               
               
                   
                   
                 TTDKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLY 
               
               
                   
                   
                 LEIIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKSIPLRRQVTVSA 
               
               
                   
                   
                 DSSASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVLGKPLGEGC 
               
               
                   
                   
                 FGQVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKNII 
               
               
                   
                   
                 NLLGACTQDGPLYV IVEYASKGNLR EYLQARRPPGLEYCYNPSHNPEEQLSSKDLVS 
               
               
                   
                   
                 CAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTN 
               
               
                   
                   
                 GRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEG 
               
               
                   
                   
                 HRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPL 
               
               
                   
                   
                 DQYSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 CTTGCGGCCACAGGCGCGGCGTCCTCGGCGGCGGGCGGCAGCTAGCGGGAGCCGGGA 
               
               
                 NO: 13 
                 isoform 7 
                 CGCCGGTGCAGCCGCAGCGCGCGGAGGAACCCGGGTGTGCCGGGAGCTGGGCGGCCA 
               
               
                   
                 Nucleic acid 
                 CGTCCGGACGGGACCGAGACCCCTCGTAGCGCATTGCGGCGACCTCGCCTTCCCCGG 
               
               
                   
                 sequence 
                 CCGCGAGCGCGCCGCTGCTTGAAAAGCCGCGGAACCCAAGGACTTTTCTCCGGTCCG 
               
               
                   
                   
                 AGCTCGGGGCGCCCCGCAGGGCGCACGGTACCCGTGCTGCAGTCGGGCACGCCGCGG 
               
               
                   
                   
                 CGCCGGGGCCTCCGCAGGGCGATGGAGCCCGGTCTGCAAGGAAAGTGAGGCGCCGCC 
               
               
                   
                   
                 GCTGCGTTCTGGAGGAGGGGGGCACAAGGTCTGGAGACCCCGGGTGGCGGACGGGAG 
               
               
                   
                   
                 CCCTCCCCCCGCCCCGCCTCCGGGGCACCAGCTCCGGCTCCATTGTTCCCGCCCGGG 
               
               
                   
                   
                 CTGGAGGCGCCGAGCACCGAGCGCCGCCGGGAGTCGAGCGCCGGCCGCGGAGCTCTT 
               
               
                   
                   
                 GCGACCCCGCCAGGACCCGAACAGAGCCCGGGGGCGGCGGGCCGGAGCCGGGGACGC 
               
               
                   
                   
                 GGGCACACGCCCGCTCGCACAAGCCACGGCGGACTCTCCCGAGGCGGAACCTCCACG 
               
               
                   
                   
                 CCGAGCGAGGGTCAGTTTGAAAAGGAGGATCGAGCTCACTGTGGAGTATCCATGGAG 
               
               
                   
                   
                 ATGTGGAGCCTTGTCACCAACCTCTAACTGCAGAACTGGGATGTGGAGCTGGAAGTG 
               
               
                   
                   
                 CCTCCTCTTCTGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCCGTCCCC 
               
               
                   
                   
                 GACCTTGCCTGAACAAGATGCTCTCCCCTCCTCGGAGGATGATGATGATGATGATGA 
               
               
                   
                   
                 CTCCTCTTCAGAGGAGAAAGAAACAGATAACACCAAACCAAACCCCGTAGCTCCATA 
               
               
                   
                   
                 TTGGACATCCCCAGAAAAGATGGAAAAGAAATTGCATGCAGTGCCGGCTGCCAAGAC 
               
               
                   
                   
                 AGTGAAGTTCAAATGCCCTTCCAGTGGGACCCCAAACCCCACACTGCGCTGGTTGAA 
               
               
                   
                   
                 AAATGGCAAAGAATTCAAACCTGACCACAGAATTGGAGGCTACAAGGTCCGTTATGC 
               
               
                   
                   
                 CACCTGGAGCATCATAATGGACTCTGTGGTGCCCTCTGACAAGGGCAACTACACCTG 
               
               
                   
                   
                 CATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCAGCTGGATGTCGTGGA 
               
               
                   
                   
                 GCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGCCAACAAAACAGTGGC 
               
               
                   
                   
                 CCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGACCCGCAGCCGCACAT 
               
               
                   
                   
                 CCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGGCCCAGACAACCTGCC 
               
               
                   
                   
                 TTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGACAAAGAGATGGAGGT 
               
               
                   
                   
                 GCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTATACGTGCTTGGCGGG 
               
               
                   
                   
                 TAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGTTCTGGAAGCCCTGGA 
               
               
                   
                   
                 AGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGATCATCATCTATTGCAC 
               
               
                   
                   
                 AGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGTCTACAAGATGAAGAG 
               
               
                   
                   
                 TGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCACAAGCTGGCCAAGAG 
               
               
                   
                   
                 CATCCCTCTGCGCAGACAGGTAACAGTGTCTGCTGACTCCAGTGCATCCATGAACTC 
               
               
                   
                   
                 TGGGGTTCTTCTGGTTCGGCCATCACGGCTCTCCTCCAGTGGGACTCCCATGCTAGC 
               
               
                   
                   
                 AGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGAGCTGCCTCGGGACAG 
               
               
                   
                   
                 ACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCTTTGGGCAGGTGGTGTTGGCAGA 
               
               
                   
                   
                 GGCTATCGGGCTGGACAAGGACAAACCCAACCGTGTGACCAAAGTGGCTGTGAAGAT 
               
               
                   
                   
                 GTTGAAGTCGGACGCAACAGAGAAAGACTTGTCAGACCTGATCTCAGAAATGGAGAT 
               
               
                   
                   
                 GATGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCTGGGGGCCTGCACGCA 
               
               
                   
                   
                 GGATGGTCCCTTGTATGTCATCGTGGAGTATGCCTCCAAGGGCAACCTGCGGGAGTA 
               
               
                   
                   
                 CCTGCAGGCCCGGAGGCCCCCAGGGCTGGAATACTGCTACAACCCCAGCCACAACCC 
               
               
                   
                   
                 AGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTACCAGGTGGCCCGAGG 
               
               
                   
                   
                 CATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACCTGGCAGCCAGGAATGT 
               
               
                   
                   
                 CCTGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTTGGCCTCGCACGGGACAT 
               
               
                   
                   
                 TCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGAAGTGGAT 
               
               
                   
                   
                 GGCACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAGTGATGTGTGGTCTTT 
               
               
                   
                   
                 CGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCCATACCCCGGTGTGCC 
               
               
                   
                   
                 TGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCATGGACAAGCCCAGTAA 
               
               
                   
                   
                 CTGCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCATGCAGTGCCCTCACA 
               
               
                   
                   
                 GAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCATCGTGGCCTTGACCTC 
               
               
                   
                   
                 CAACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTACTCCCCCAGCTTTCC 
               
               
                   
                   
                 CGACACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGTCTTCTCTCATGAGCC 
               
               
                   
                   
                 GCTGCCCGAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCTTGCCAATGGCGGACT 
               
               
                   
                   
                 CAAACGCCGCTGACTGCCACCCACACGCCCTCCCCAGACTCCACCGTCAGCTGTAAC 
               
               
                   
                   
                 CCTCACCCACAGCCCCTGCTGGGCCCACCACCTGTCCGTCCCTGTCCCCTTTCCTGC 
               
               
                   
                   
                 TGGCAGGAGCCGGCTGCCTACCAGGGGCCTTCCTGTGTGGCCTGCCTTCACCCCACT 
               
               
                   
                   
                 CAGCTCACCTCTCCCTCCACCTCCTCTCCACCTGCTGGTGAGAGGTGCAAAGAGGCA 
               
               
                   
                   
                 GATCTTTGCTGCCAGCCACTTCATCCCCTCCCAGATGTTGGACCAACACCCCTCCCT 
               
               
                   
                   
                 GCCACCAGGCACTGCCTGGAGGGCAGGGAGTGGGAGCCAATGAACAGGCATGCAAGT 
               
               
                   
                   
                 GAGAGCTTCCTGAGCTTTCTCCTGTCGGTTTGGTCTGTTTTGCCTTCACCCATAAGC 
               
               
                   
                   
                 CCCTCGCACTCTGGTGGCAGGTGCCTTGTCCTCAGGGCTACAGCAGTAGGGAGGTCA 
               
               
                   
                   
                 GTGCTTCGTGCCTCGATTGAAGGTGACCTCTGCCCCAGATAGGTGGTGCCAGTGGCT 
               
               
                   
                   
                 TATTAATTCCGATACTAGTTTGCTTTGCTGACCAAATGCCTGGTACCAGAGGATGGT 
               
               
                   
                   
                 GAGGCGAAGGCCAGGTTGGGGGCAGTGTTGTGGCCCTGGGGCCCAGCCCCAAACTGG 
               
               
                   
                   
                 GGGCTCTGTATATAGCTATGAAGAAAACACAAAGTGTATAAATCTGAGTATATATTT 
               
               
                   
                   
                 ACATGTCTTTTTAAAAGGGTCGTTACCAGAGATTTACCCATCGGGTAAGATGCTCCT 
               
               
                   
                   
                 GGTGGCTGGGAGGCATCAGTTGCTATATATTAAAAACAAAAAAGAAAAAAAAGGAAA 
               
               
                   
                   
                 ATGTTTTTAAAAAGGTCATATATTTTTTGCTACTTTTGCTGTTTTATTTTTTTAAAT 
               
               
                   
                   
                 TATGTTCTAAACCTATTTTCAGTTTAGGTCCCTCAATAAAAATTGCTGCTGCTT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQDALPSSEDDDDDDDSSSEEKETDNTKP 
               
               
                 NO: 14 
                 isoform 7 
                 NPVAPYWTSPEKMEKKLHAVPAAKTVKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGG 
               
               
                   
                 Amino acid 
                 YKVRYATWSIIMDSVVPSDKGNYTCIVENEYGSINHTYQLDVVERSPHRPILQAGLP 
               
               
                   
                 sequence 
                 ANKTVALGSNVEFMCKVYSDPQPHIQWLKHIEVNGSKIGPDNLPYVQILKTAGVNTT 
               
               
                   
                   
                 DKEMEVLHLRNVSFEDAGEYTCLAGNSIGLSHHSAWLTVLEALEERPAVMTSPLYLE 
               
               
                   
                   
                 IIIYCTGAFLISCMVGSVIVYKMKSGTKKSDFHSQMAVHKLAKSIPLRRQVTVSADS 
               
               
                   
                   
                 SASMNSGVLLVRPSRLSSSGTPMLAGVSEYELPEDPRWELPRDRLVLGKPLGEGCFG 
               
               
                   
                   
                 QVVLAEAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKNIINL 
               
               
                   
                   
                 LGACTQDGPLYV IVEYASKGNLR EYLQARRPPGLEYCYNPSHNPEEQLSSKDLVSCA 
               
               
                   
                   
                 YQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGR 
               
               
                   
                   
                 LPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHR 
               
               
                   
                   
                 MDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQ 
               
               
                   
                   
                 YSPSFPDTRSSTCSSGEDSVFSHEPLPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 GCTTTGCCCGCCGCAGCCCAGCCGGGGCCGGCGCCTCCCTCCGCTCGCCGCCCGCCC 
               
               
                 NO: 15 
                 isoform 8 
                 CTTTCACCTCCTGGCTCCCTCCCGGGCGATCCGCGCCCCTTGGGTCTCCCCTCCCTT 
               
               
                   
                 Nucleic acid 
                 CCCTCCGTCCGCGTCTCCTGCGCCCCCTCCCTGCGCTCGTCCCGCCGCTCTTCCCGC 
               
               
                   
                 sequence 
                 CGCCCAACTTTTCCTCCAACTCGCGCTCGGGAGCTGGCGAGGCGGCGGCGGCTCCTC 
               
               
                   
                   
                 AGGTCAGTTTGAAAAGGAGGATCGAGCTCACTGTGGAGTATCCATGGAGATGTGGAG 
               
               
                   
                   
                 CCTTGTCACCAACCTCTAACTGCAGAACTGGGATGTGGAGCTGGAAGTGCCTCCTCT 
               
               
                   
                   
                 TCTGGGCTGTGCTGGTCACAGCCACACTCTGCACCGCTAGGCCGTCCCCGACCTTGC 
               
               
                   
                   
                 CTGAACAAGCCCAGCCCTGGGGAGCCCCTGTGGAAGTGGAGTCCTTCCTGGTCCACC 
               
               
                   
                   
                 CCGGTGACCTGCTGCAGCTTCGCTGTCGGCTGCGGGACGATGTGCAGAGCATCAACT 
               
               
                   
                   
                 GGCTGCGGGACGGGGTGCAGCTGGCGGAAAGCAACCGCACCCGCATCACAGGGGAGG 
               
               
                   
                   
                 AGGTGGAGGTGCAGGACTCCGTGCCCGCAGACTCCGGCCTCTATGCTTGCGTAACCA 
               
               
                   
                   
                 GCAGCCCCTCGGGCAGTGACACCACCTACTTCTCCGTCAATGTTTCAGATGCTCTCC 
               
               
                   
                   
                 CCTCCTCGGAGGATGATGATGATGATGATGACTCCTCTTCAGAGGAGAAAGAAACAG 
               
               
                   
                   
                 ATAACACCAAACCAAACCCCGTAGCTCCATATTGGACATCCCCAGAAAAGATGGAAA 
               
               
                   
                   
                 AGAAATTGCATGCAGTGCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCCAGTG 
               
               
                   
                   
                 GGACCCCAAACCCCACACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAACCTGACC 
               
               
                   
                   
                 ACAGAATTGGAGGCTACAAGGTCCGTTATGCCACCTGGAGCATCATAATGGACTCTG 
               
               
                   
                   
                 TGGTGCCCTCTGACAAGGGCAACTACACCTGCATTGTGGAGAATGAGTACGGCAGCA 
               
               
                   
                   
                 TCAACCACACATACCAGCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATCCTGC 
               
               
                   
                   
                 AAGCAGGGTTGCCCGCCAACAAAACAGTGGCCCTGGGTAGCAACGTGGAGTTCATGT 
               
               
                   
                   
                 GTAAGGTGTACAGTGACCCGCAGCCGCACATCCAGTGGCTAAAGCACATCGAGGTGA 
               
               
                   
                   
                 ATGGGAGCAAGATTGGCCCAGACAACCTGCCTTATGTCCAGATCTTGAAGACTGCTG 
               
               
                   
                   
                 GAGTTAATACCACCGACAAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCCTTTG 
               
               
                   
                   
                 AGGACGCAGGGGAGTATACGTGCTTGGCGGGTAACTCTATCGGACTCTCCCATCACT 
               
               
                   
                   
                 CTGCATGGTTGACCGTTCTGGAAGCCCTGGAAGAGAGGCCGGCAGTGATGACCTCGC 
               
               
                   
                   
                 CCCTGTACCTGGAGATCATCATCTATTGCACAGGGGCCTTCCTCATCTCCTGCATGG 
               
               
                   
                   
                 TGGGGTCGGTCATCGTCTACAAGATGAAGAGTGGTACCAAGAAGAGTGACTTCCACA 
               
               
                   
                   
                 GCCAGATGGCTGTGCACAAGCTGGCCAAGAGCATCCCTCTGCGCAGACAGGTAACAG 
               
               
                   
                   
                 TGTCTGCTGACTCCAGTGCATCCATGAACTCTGGGGTTCTTCTGGTTCGGCCATCAC 
               
               
                   
                   
                 GGCTCTCCTCCAGTGGGACTCCCATGCTAGCAGGGGTCTCTGAGTATGAGCTTCCCG 
               
               
                   
                   
                 AAGACCCTCGCTGGGAGCTGCCTCGGGACAGACTGGTCTTAGGCAAACCCCTGGGAG 
               
               
                   
                   
                 AGGGCTGCTTTGGGCAGGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAGGACAAAC 
               
               
                   
                   
                 CCAACCGTGTGACCAAAGTGGCTGTGAAGATGTTGAAGTCGGACGCAACAGAGAAAG 
               
               
                   
                   
                 ACTTGTCAGACCTGATCTCAGAAATGGAGATGATGAAGATGATCGGGAAGCATAAGA 
               
               
                   
                   
                 ATATCATCAACCTGCTGGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATCGTGG 
               
               
                   
                   
                 AGTATGCCTCCAAGGGCAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCCCCAGGGC 
               
               
                   
                   
                 TGGAATACTGCTACAACCCCAGCCACAACCCAGAGGAGCAGCTCTCCTCCAAGGACC 
               
               
                   
                   
                 TGGTGTCCTGCGCCTACCAGGTGGCCCGAGGCATGGAGTATCTGGCCTCCAAGAAGT 
               
               
                   
                   
                 GCATACACCGAGACCTGGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTGATGA 
               
               
                   
                   
                 AGATAGCAGACTTTGGCCTCGCACGGGACATTCACCACATCGACTACTATAAAAAGA 
               
               
                   
                   
                 CAACCAACGGCCGACTGCCTGTGAAGTGGATGGCACCCGAGGCATTATTTGACCGGA 
               
               
                   
                   
                 TCTACACCCACCAGAGTGATGTGTGGTCTTTCGGGGTGCTCCTGTGGGAGATCTTCA 
               
               
                   
                   
                 CTCTGGGCGGCTCCCCATACCCCGGTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGA 
               
               
                   
                   
                 AGGAGGGTCACCGCATGGACAAGCCCAGTAACTGCACCAACGAGCTGTACATGATGA 
               
               
                   
                   
                 TGCGGGACTGCTGGCATGCAGTGCCCTCACAGAGACCCACCTTCAAGCAGCTGGTGG 
               
               
                   
                   
                 AAGACCTGGACCGCATCGTGGCCTTGACCTCCAACCAGGAGTACCTGGACCTGTCCA 
               
               
                   
                   
                 TGCCCCTGGACCAGTACTCCCCCAGCTTTCCCGACACCCGGAGCTCTACGTGCTCCT 
               
               
                   
                   
                 CAGGGGAGGATTCCGTCTTCTCTCATGAGCCGCTGCCCGAGGAGCCCTGCCTGCCCC 
               
               
                   
                   
                 GACACCCAGCCCAGCTTGCCAATGGCGGACTCAAACGCCGCTGACTGCCACCCACAC 
               
               
                   
                   
                 GCCCTCCCCAGACTCCACCGTCAGCTGTAACCCTCACCCACAGCCCCTGCTGGGCCC 
               
               
                   
                   
                 ACCACCTGTCCGTCCCTGTCCCCTTTCCTGCTGGCAGGAGCCGGCTGCCTACCAGGG 
               
               
                   
                   
                 GCCTTCCTGTGTGGCCTGCCTTCACCCCACTCAGCTCACCTCTCCCTCCACCTCCTC 
               
               
                   
                   
                 TCCACCTGCTGGTGAGAGGTGCAAAGAGGCAGATCTTTGCTGCCAGCCACTTCATCC 
               
               
                   
                   
                 CCTCCCAGATGTTGGACCAACACCCCTCCCTGCCACCAGGCACTGCCTGGAGGGCAG 
               
               
                   
                   
                 GGAGTGGGAGCCAATGAACAGGCATGCAAGTGAGAGCTTCCTGAGCTTTCTCCTGTC 
               
               
                   
                   
                 GGTTTGGTCTGTTTTGCCTTCACCCATAAGCCCCTCGCACTCTGGTGGCAGGTGCCT 
               
               
                   
                   
                 TGTCCTCAGGGCTACAGCAGTAGGGAGGTCAGTGCTTCGTGCCTCGATTGAAGGTGA 
               
               
                   
                   
                 CCTCTGCCCCAGATAGGTGGTGCCAGTGGCTTATTAATTCCGATACTAGTTTGCTTT 
               
               
                   
                   
                 GCTGACCAAATGCCTGGTACCAGAGGATGGTGAGGCGAAGGCCAGGTTGGGGGCAGT 
               
               
                   
                   
                 GTTGTGGCCCTGGGGCCCAGCCCCAAACTGGGGGCTCTGTATATAGCTATGAAGAAA 
               
               
                   
                   
                 ACACAAAGTGTATAAATCTGAGTATATATTTACATGTCTTTTTAAAAGGGTCGTTAC 
               
               
                   
                   
                 CAGAGATTTACCCATCGGGTAAGATGCTCCTGGTGGCTGGGAGGCATCAGTTGCTAT 
               
               
                   
                   
                 ATATTAAAAACAAAAAAGAAAAAAAAGGAAAATGTTTTTAAAAAGGTCATATATTTT 
               
               
                   
                   
                 TTGCTACTTTTGCTGTTTTATTTTTTTAAATTATGTTCTAAACCTATTTTCAGTTTA 
               
               
                   
                   
                 GGTCCCTCAATAAAAATTGCTGCTGCTTCATT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRL 
               
               
                 NO: 16 
                 isoform 8 
                 RDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYF 
               
               
                   
                 Amino acid 
                 SVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNPVAPYWTSPEKMEKKLHAVPAAKT 
               
               
                   
                 sequence 
                 VKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTC 
               
               
                   
                   
                 IVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHI 
               
               
                   
                   
                 QWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAG 
               
               
                   
                   
                 NSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKS 
               
               
                   
                   
                 GTKKSDFHSQMAVHKLAKSIPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLA 
               
               
                   
                   
                 GVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKM 
               
               
                   
                   
                 LKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR EY 
               
               
                   
                   
                 LQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNV 
               
               
                   
                   
                 LVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSF 
               
               
                   
                   
                 GVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQ 
               
               
                   
                   
                 RPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEP 
               
               
                   
                   
                 LPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 AACTTTTCCTCCAACTCGCGCTCGGGAGCTGGCGAGGCGGCGGCGGCTCCTCAAAGT 
               
               
                 NO: 17 
                 isoform 9 
                 GGGAGAGCTTCAAGGTCACGTGGTCCGTCCAGCCCCTGCTATCTCACCAGACACTGT 
               
               
                   
                 Nucleic acid 
                 CCACCCTGTATGTTGGATCAGTACTCCAGTGAGAAGACAGCAGGCACTTTCACCCAT 
               
               
                   
                 sequence 
                 GCAGCCCATTCAGTCTTCATAACCACCTGTGATGGAGGCAAGGGTCAGTTTGAAAAG 
               
               
                   
                   
                 GAGGATCGAGCTCACTGTGGAGTATCCATGGAGATGTGGAGCCTTGTCACCAACCTC 
               
               
                   
                   
                 TAACTGCAGAACTGGGATGTGGAGCTGGAAGTGCCTCCTCTTCTGGGCTGTGCTGGT 
               
               
                   
                   
                 CACAGCCACACTCTGCACCGCTAGGCCGTCCCCGACCTTGCCTGAACAAGCCCAGCC 
               
               
                   
                   
                 CTGGGGAGCCCCTGTGGAAGTGGAGTCCTTCCTGGTCCACCCCGGTGACCTGCTGCA 
               
               
                   
                   
                 GCTTCGCTGTCGGCTGCGGGACGATGTGCAGAGCATCAACTGGCTGCGGGACGGGGT 
               
               
                   
                   
                 GCAGCTGGCGGAAAGCAACCGCACCCGCATCACAGGGGAGGAGGTGGAGGTGCAGGA 
               
               
                   
                   
                 CTCCGTGCCCGCAGACTCCGGCCTCTATGCTTGCGTAACCAGCAGCCCCTCGGGCAG 
               
               
                   
                   
                 TGACACCACCTACTTCTCCGTCAATGTTTCAGATGCTCTCCCCTCCTCGGAGGATGA 
               
               
                   
                   
                 TGATGATGATGATGACTCCTCTTCAGAGGAGAAAGAAACAGATAACACCAAACCAAA 
               
               
                   
                   
                 CCCCGTAGCTCCATATTGGACATCCCCAGAAAAGATGGAAAAGAAATTGCATGCAGT 
               
               
                   
                   
                 GCCGGCTGCCAAGACAGTGAAGTTCAAATGCCCTTCCAGTGGGACCCCAAACCCCAC 
               
               
                   
                   
                 ACTGCGCTGGTTGAAAAATGGCAAAGAATTCAAACCTGACCACAGAATTGGAGGCTA 
               
               
                   
                   
                 CAAGGTCCGTTATGCCACCTGGAGCATCATAATGGACTCTGTGGTGCCCTCTGACAA 
               
               
                   
                   
                 GGGCAACTACACCTGCATTGTGGAGAATGAGTACGGCAGCATCAACCACACATACCA 
               
               
                   
                   
                 GCTGGATGTCGTGGAGCGGTCCCCTCACCGGCCCATCCTGCAAGCAGGGTTGCCCGC 
               
               
                   
                   
                 CAACAAAACAGTGGCCCTGGGTAGCAACGTGGAGTTCATGTGTAAGGTGTACAGTGA 
               
               
                   
                   
                 CCCGCAGCCGCACATCCAGTGGCTAAAGCACATCGAGGTGAATGGGAGCAAGATTGG 
               
               
                   
                   
                 CCCAGACAACCTGCCTTATGTCCAGATCTTGAAGACTGCTGGAGTTAATACCACCGA 
               
               
                   
                   
                 CAAAGAGATGGAGGTGCTTCACTTAAGAAATGTCTCCTTTGAGGACGCAGGGGAGTA 
               
               
                   
                   
                 TACGTGCTTGGCGGGTAACTCTATCGGACTCTCCCATCACTCTGCATGGTTGACCGT 
               
               
                   
                   
                 TCTGGAAGCCCTGGAAGAGAGGCCGGCAGTGATGACCTCGCCCCTGTACCTGGAGAT 
               
               
                   
                   
                 CATCATCTATTGCACAGGGGCCTTCCTCATCTCCTGCATGGTGGGGTCGGTCATCGT 
               
               
                   
                   
                 CTACAAGATGAAGAGTGGTACCAAGAAGAGTGACTTCCACAGCCAGATGGCTGTGCA 
               
               
                   
                   
                 CAAGCTGGCCAAGAGCATCCCTCTGCGCAGACAGGTAACAGTGTCTGCTGACTCCAG 
               
               
                   
                   
                 TGCATCCATGAACTCTGGGGTTCTTCTGGTTCGGCCATCACGGCTCTCCTCCAGTGG 
               
               
                   
                   
                 GACTCCCATGCTAGCAGGGGTCTCTGAGTATGAGCTTCCCGAAGACCCTCGCTGGGA 
               
               
                   
                   
                 GCTGCCTCGGGACAGACTGGTCTTAGGCAAACCCCTGGGAGAGGGCTGCTTTGGGCA 
               
               
                   
                   
                 GGTGGTGTTGGCAGAGGCTATCGGGCTGGACAAGGACAAACCCAACCGTGTGACCAA 
               
               
                   
                   
                 AGTGGCTGTGAAGATGTTGAAGTCGGACGCAACAGAGAAAGACTTGTCAGACCTGAT 
               
               
                   
                   
                 CTCAGAAATGGAGATGATGAAGATGATCGGGAAGCATAAGAATATCATCAACCTGCT 
               
               
                   
                   
                 GGGGGCCTGCACGCAGGATGGTCCCTTGTATGTCATCGTGGAGTATGCCTCCAAGGG 
               
               
                   
                   
                 CAACCTGCGGGAGTACCTGCAGGCCCGGAGGCCCCCAGGGCTGGAATACTGCTACAA 
               
               
                   
                   
                 CCCCAGCCACAACCCAGAGGAGCAGCTCTCCTCCAAGGACCTGGTGTCCTGCGCCTA 
               
               
                   
                   
                 CCAGGTGGCCCGAGGCATGGAGTATCTGGCCTCCAAGAAGTGCATACACCGAGACCT 
               
               
                   
                   
                 GGCAGCCAGGAATGTCCTGGTGACAGAGGACAATGTGATGAAGATAGCAGACTTTGG 
               
               
                   
                   
                 CCTCGCACGGGACATTCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACT 
               
               
                   
                   
                 GCCTGTGAAGTGGATGGCACCCGAGGCATTATTTGACCGGATCTACACCCACCAGAG 
               
               
                   
                   
                 TGATGTGTGGTCTTTCGGGGTGCTCCTGTGGGAGATCTTCACTCTGGGCGGCTCCCC 
               
               
                   
                   
                 ATACCCCGGTGTGCCTGTGGAGGAACTTTTCAAGCTGCTGAAGGAGGGTCACCGCAT 
               
               
                   
                   
                 GGACAAGCCCAGTAACTGCACCAACGAGCTGTACATGATGATGCGGGACTGCTGGCA 
               
               
                   
                   
                 TGCAGTGCCCTCACAGAGACCCACCTTCAAGCAGCTGGTGGAAGACCTGGACCGCAT 
               
               
                   
                   
                 CGTGGCCTTGACCTCCAACCAGGAGTACCTGGACCTGTCCATGCCCCTGGACCAGTA 
               
               
                   
                   
                 CTCCCCCAGCTTTCCCGACACCCGGAGCTCTACGTGCTCCTCAGGGGAGGATTCCGT 
               
               
                   
                   
                 CTTCTCTCATGAGCCGCTGCCCGAGGAGCCCTGCCTGCCCCGACACCCAGCCCAGCT 
               
               
                   
                   
                 TGCCAATGGCGGACTCAAACGCCGCTGACTGCCACCCACACGCCCTCCCCAGACTCC 
               
               
                   
                   
                 ACCGTCAGCTGTAACCCTCACCCACAGCCCCTGCTGGGCCCACCACCTGTCCGTCCC 
               
               
                   
                   
                 TGTCCCCTTTCCTGCTGGCA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 MWSWKCLLFWAVLVTATLCTARPSPTLPEQAQPWGAPVEVESFLVHPGDLLQLRCRL 
               
               
                 NO: 18 
                 isoform 9 
                 RDDVQSINWLRDGVQLAESNRTRITGEEVEVQDSVPADSGLYACVTSSPSGSDTTYF 
               
               
                   
                 Amino acid 
                 SVNVSDALPSSEDDDDDDDSSSEEKETDNTKPNPVAPYWTSPEKMEKKLHAVPAAKT 
               
               
                   
                 sequence 
                 VKFKCPSSGTPNPTLRWLKNGKEFKPDHRIGGYKVRYATWSIIMDSVVPSDKGNYTC 
               
               
                   
                   
                 IVENEYGSINHTYQLDVVERSPHRPILQAGLPANKTVALGSNVEFMCKVYSDPQPHI 
               
               
                   
                   
                 QWLKHIEVNGSKIGPDNLPYVQILKTAGVNTTDKEMEVLHLRNVSFEDAGEYTCLAG 
               
               
                   
                   
                 NSIGLSHHSAWLTVLEALEERPAVMTSPLYLEIIIYCTGAFLISCMVGSVIVYKMKS 
               
               
                   
                   
                 GTKKSDFHSQMAVHKLAKSIPLRRQVTVSADSSASMNSGVLLVRPSRLSSSGTPMLA 
               
               
                   
                   
                 GVSEYELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVTKVAVKM 
               
               
                   
                   
                 LKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR EY 
               
               
                   
                   
                 LQARRPPGLEYCYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNV 
               
               
                   
                   
                 LVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSF 
               
               
                   
                   
                 GVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQ 
               
               
                   
                   
                 RPTFKQLVEDLDRIVALTSNQEYLDLSMPLDQYSPSFPDTRSSTCSSGEDSVFSHEP 
               
               
                   
                   
                 LPEEPCLPRHPAQLANGGLKRR 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 GGCGGCGGCTGGAGGAGAGCGCGGTGGAGAGCCGAGCGGGCGGGCGGCGGGTGCGGA 
               
               
                 NO: 19 
                 isoform 1 
                 GCGGGCGAGGGAGCGCGCGCGGCCGCCACAAAGCTCGGGCGCCGCGGGGCTGCATGC 
               
               
                   
                 Nucleic acid 
                 GGCGTACCTGGCCCGGCGCGGCGACTGCTCTCCGGGCTGGCGGGGGCCGGCCGCGAG 
               
               
                   
                 sequence 
                 CCCCGGGGGCCCCGAGGCCGCAGCTTGCCTGCGCGCTCTGAGCCTTCGCAACTCGCG 
               
               
                   
                   
                 AGCAAAGTTTGGTGGAGGCAACGCCAAGCCTGAGTCCTTTCTTCCTCTCGTTCCCCA 
               
               
                   
                   
                 AATCCGAGGGCAGCCCGCGGGCGTCATGCCCGCGCTCCTCCGCAGCCTGGGGTACGC 
               
               
                   
                   
                 GTGAAGCCCGGGAGGCTTGGCGCCGGCGAAGACCCAAGGACCACTCTTCTGCGTTTG 
               
               
                   
                   
                 GAGTTGCTCCCCGCAACCCCGGGCTCGTCGCTTTCTCCATCCCGACCCACGCGGGGC 
               
               
                   
                   
                 GCGGGGACAACACAGGTCGCGGAGGAGCGTTGCCATTCAAGTGACTGCAGCAGCAGC 
               
               
                   
                   
                 GGCAGCGCCTCGGTTCCTGAGCCCACCGCAGGCTGAAGGCATTGCGCGTAGTCCATG 
               
               
                   
                   
                 CCCGTAGAGGAAGTGTGCAGATGGGATTAACGTCCACATGGAGATATGGAAGAGGAC 
               
               
                   
                   
                 CGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTCATCTGCCTGGTCGTGG 
               
               
                   
                   
                 TCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTTAGTTGAGGATACCA 
               
               
                   
                   
                 CATTAGAGCCAGAAGATGCCATCTCATCCGGAGATGATGAGGATGACACCGATGGTG 
               
               
                   
                   
                 CGGAAGATTTTGTCAGTGAGAACAGTAACAACAAGAGAGCACCATACTGGACCAACA 
               
               
                   
                   
                 CAGAAAAGATGGAAAAGCGGCTCCATGCTGTGCCTGCGGCCAACACTGTCAAGTTTC 
               
               
                   
                   
                 GCTGCCCAGCCGGGGGGAACCCAATGCCAACCATGCGGTGGCTGAAAAACGGGAAGG 
               
               
                   
                   
                 AGTTTAAGCAGGAGCATCGCATTGGAGGCTACAAGGTACGAAACCAGCACTGGAGCC 
               
               
                   
                   
                 TCATTATGGAAAGTGTGGTCCCATCTGACAAGGGAAATTATACCTGTGTAGTGGAGA 
               
               
                   
                   
                 ATGAATACGGGTCCATCAATCACACGTACCACCTGGATGTTGTGGAGCGATCGCCTC 
               
               
                   
                   
                 ACCGGCCCATCCTCCAAGCCGGACTGCCGGCAAATGCCTCCACAGTGGTCGGAGGAG 
               
               
                   
                   
                 ACGTAGAGTTTGTCTGCAAGGTTTACAGTGATGCCCAGCCCCACATCCAGTGGATCA 
               
               
                   
                   
                 AGCACGTGGAAAAGAACGGCAGTAAATACGGGCCCGACGGGCTGCCCTACCTCAAGG 
               
               
                   
                   
                 TTCTCAAGGCCGCCGGTGTTAACACCACGGACAAAGAGATTGAGGTTCTCTATATTC 
               
               
                   
                   
                 GGAATGTAACTTTTGAGGACGCTGGGGAATATACGTGCTTGGCGGGTAATTCTATTG 
               
               
                   
                   
                 GGATATCCTTTCACTCTGCATGGTTGACAGTTCTGCCAGCGCCTGGAAGAGAAAAGG 
               
               
                   
                   
                 AGATTACAGCTTCCCCAGACTACCTGGAGATAGCCATTTACTGCATAGGGGTCTTCT 
               
               
                   
                   
                 TAATCGCCTGTATGGTGGTAACAGTCATCCTGTGCCGAATGAAGAACACGACCAAGA 
               
               
                   
                   
                 AGCCAGACTTCAGCAGCCAGCCGGCTGTGCACAAGCTGACCAAACGTATCCCCCTGC 
               
               
                   
                   
                 GGAGACAGGTAACAGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAACACCCCGC 
               
               
                   
                   
                 TGGTGAGGATAACAACACGCCTCTCTTCAACGGCAGACACCCCCATGCTGGCAGGGG 
               
               
                   
                   
                 TCTCCGAGTATGAACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGATAAGCTGA 
               
               
                   
                   
                 CACTGGGCAAGCCCCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCGGAAGCAG 
               
               
                   
                   
                 TGGGAATTGACAAAGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAGATGTTGA 
               
               
                   
                   
                 AAGATGATGCCACAGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAGATGATGA 
               
               
                   
                   
                 AGATGATTGGGAAACACAAGAATATCATAAATCTTCTTGGAGCCTGCACACAGGATG 
               
               
                   
                   
                 GGCCTCTCTATGTCATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAATACCTCC 
               
               
                   
                   
                 GAGCCCGGAGGCCACCCGGGATGGAGTACTCCTATGACATTAACCGTGTTCCTGAGG 
               
               
                   
                   
                 AGCAGATGACCTTCAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGAGGCATGG 
               
               
                   
                   
                 AGTACTTGGCTTCCCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAATGTTTTGG 
               
               
                   
                   
                 TAACAGAAAACAATGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGATATCAACA 
               
               
                   
                   
                 ATATAGACTATTACAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGGATGGCTC 
               
               
                   
                   
                 CAGAAGCCCTGTTTGATAGAGTATACACTCATCAGAGTGATGTCTGGTCCTTCGGGG 
               
               
                   
                   
                 TGTTAATGTGGGAGATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATTCCCGTGG 
               
               
                   
                   
                 AGGAACTTTTTAAGCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCCAACTGCA 
               
               
                   
                   
                 CCAACGAACTGTACATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGAC 
               
               
                   
                   
                 CAACGTTCAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACAACCAATG 
               
               
                   
                   
                 AGGAATACTTGGACCTCAGCCAACCTCTCGAACAGTATTCACCTAGTTACCCTGACA 
               
               
                   
                   
                 CAAGAAGTTCTTGTTCTTCAGGAGATGATTCTGTTTTTTCTCCAGACCCCATGCCTT 
               
               
                   
                   
                 ACGAACCATGCCTTCCTCAGTATCCACACATAAACGGCAGTGTTAAAACATGAATGA 
               
               
                   
                   
                 CTGTGTCTGCCTGTCCCCAAACAGGACAGCACTGGGAACCTAGCTACACTGAGCAGG 
               
               
                   
                   
                 GAGACCATGCCTCCCAGAGCTTGTTGTCTCCACTTGTATATATGGATCAGAGGAGTA 
               
               
                   
                   
                 AATAATTGGAAAAGTAATCAGCATATGTGTAAAGATTTATACAGTTGAAAACTTGTA 
               
               
                   
                   
                 ATCTTCCCCAGGAGGAGAAGAAGGTTTCTGGAGCAGTGGACTGCCACAAGCCACCAT 
               
               
                   
                   
                 GTAACCCCTCTCACCTGCCGTGCGTACTGGCTGTGGACCAGTAGGACTCAAGGTGGA 
               
               
                   
                   
                 CGTGCGTTCTGCCTTCCTTGTTAATTTTGTAATAATTGGAGAAGATTTATGTCAGCA 
               
               
                   
                   
                 CACACTTACAGAGCACAAATGCAGTATATAGGTGCTGGATGTATGTAAATATATTCA 
               
               
                   
                   
                 AATTATGTATAAATATATATTATATATTTACAAGGAGTTATTTTTTGTATTGATTTT 
               
               
                   
                   
                 AAATGGATGTCCCAATGCACCTAGAAAATTGGTCTCTCTTTTTTTAATAGCTATTTG 
               
               
                   
                   
                 CTAAATGCTGTTCTTACACATAATTTCTTAATTTTCACCGAGCAGAGGTGGAAAAAT 
               
               
                   
                   
                 ACTTTTGCTTTCAGGGAAAATGGTATAACGTTAATTTATTAATAAATTGGTAATATA 
               
               
                   
                   
                 CAAAACAATTAATCATTTATAGTTTTTTTTGTAATTTAAGTGGCATTTCTATGCAGG 
               
               
                   
                   
                 CAGCACAGCAGACTAGTTAATCTATTGCTTGGACTTAACTAGTTATCAGATCCTTTG 
               
               
                   
                   
                 AAAAGAGAATATTTACAATATATGACTAATTTGGGGAAAATGAAGTTTTGATTTATT 
               
               
                   
                   
                 TGTGTTTAAATGCTGCTGTCAGACGATTGTTCTTAGACCTCCTAAATGCCCCATATT 
               
               
                   
                   
                 AAAAGAACTCATTCATAGGAAGGTGTTTCATTTTGGTGTGCAACCCTGTCATTACGT 
               
               
                   
                   
                 CAACGCAACGTCTAACTGGACTTCCCAAGATAAATGGTACCAGCGTCCTCTTAAAAG 
               
               
                   
                   
                 ATGCCTTAATCCATTCCTTGAGGACAGACCTTAGTTGAAATGATAGCAGAATGTGCT 
               
               
                   
                   
                 TCTCTCTGGCAGCTGGCCTTCTGCTTCTGAGTTGCACATTAATCAGATTAGCCTGTA 
               
               
                   
                   
                 TTCTCTTCAGTGAATTTTGATAATGGCTTCCAGACTCTTTGGCGTTGGAGACGCCTG 
               
               
                   
                   
                 TTAGGATCTTCAAGTCCCATCATAGAAAATTGAAACACAGAGTTGTTCTGCTGATAG 
               
               
                   
                   
                 TTTTGGGGATACGTCCATCTTTTTAAGGGATTGCTTTCATCTAATTCTGGCAGGACC 
               
               
                   
                   
                 TCACCAAAAGATCCAGCCTCATACCTACATCAGACAAAATATCGCCGTTGTTCCTTC 
               
               
                   
                   
                 TGTACTAAAGTATTGTGTTTTGCTTTGGAAACACCCACTCACTTTGCAATAGCCGTG 
               
               
                   
                   
                 CAAGATGAATGCAGATTACACTGATCTTATGTGTTACAAAATTGGAGAAAGTATTTA 
               
               
                   
                   
                 ATAAAACCTGTTAATTTTTATACTGACAATAAAAATGTTTCTACAGATATTAATGTT 
               
               
                   
                   
                 AACAAGACAAAATAAATGTCACGCAACTTATTTTTTT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEDAISSGDDEDDTDGAEDFVSE 
               
               
                 NO: 20 
                 isoform 1 
                 NSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHR 
               
               
                   
                 Amino acid 
                 IGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQA 
               
               
                   
                 sequence 
                 GLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGV 
               
               
                   
                   
                 NTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLPAPGREKEITASPD 
               
               
                   
                   
                 YLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVS 
               
               
                   
                   
                 AESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLG 
               
               
                   
                   
                 EGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHK 
               
               
                   
                   
                 NIINLLGACTQDGPLYV IVEYASKGNLR EYLRARRPPGMEYSYDINRVPEEQMTFKD 
               
               
                   
                   
                 LVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKK 
               
               
                   
                   
                 TTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLL 
               
               
                   
                   
                 KEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLS 
               
               
                   
                   
                 QPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 CCCAAGGACCACTCTTCTGCGTTTGGAGTTGCTCCCCGCAACCCCGGGCTCGTCGCT 
               
               
                 NO: 21 
                 isoform 2 
                 TTCTCCATCCCGACCCACGCGGGGCGCGGGGACAACACAGGTCGCGGAGGAGCGTTG 
               
               
                   
                 Nucleic acid 
                 CCATTCAAGTGACTGCAGCAGCAGCGGCAGCGCCTCGGTTCCTGAGCCCACCGCAGG 
               
               
                   
                 sequence 
                 CTGAAGGCATTGCGCGTAGTCCATGCCCGTAGAGGAAGTGTGCAGATGGGATTAACG 
               
               
                   
                   
                 TCCACATGGAGATATGGAAGAGGACCGGGGATTGGTACCGTAACCATGGTCAGCTGG 
               
               
                   
                   
                 GGTCGTTTCATCTGCCTGGTCGTGGTCACCATGGCAACCTTGTCCCTGGCCCGGCCC 
               
               
                   
                   
                 TCCTTCAGTTTAGTTGAGGATACCACATTAGAGCCAGAAGAGCCACCAACCAAATAC 
               
               
                   
                   
                 CAAATCTCTCAACCAGAAGTGTACGTGGCTGCGCCAGGGGAGTCGCTAGAGGTGCGC 
               
               
                   
                   
                 TGCCTGTTGAAAGATGCCGCCGTGATCAGTTGGACTAAGGATGGGGTGCACTTGGGG 
               
               
                   
                   
                 CCCAACAATAGGACAGTGCTTATTGGGGAGTACTTGCAGATAAAGGGCGCCACGCCT 
               
               
                   
                   
                 AGAGACTCCGGCCTCTATGCTTGTACTGCCAGTAGGACTGTAGACAGTGAAACTTGG 
               
               
                   
                   
                 TACTTCATGGTGAATGTCACAGATGCCATCTCATCCGGAGATGATGAGGATGACACC 
               
               
                   
                   
                 GATGGTGCGGAAGATTTTGTCAGTGAGAACAGTAACAACAAGAGAGCACCATACTGG 
               
               
                   
                   
                 ACCAACACAGAAAAGATGGAAAAGCGGCTCCATGCTGTGCCTGCGGCCAACACTGTC 
               
               
                   
                   
                 AAGTTTCGCTGCCCAGCCGGGGGGAACCCAATGCCAACCATGCGGTGGCTGAAAAAC 
               
               
                   
                   
                 GGGAAGGAGTTTAAGCAGGAGCATCGCATTGGAGGCTACAAGGTACGAAACCAGCAC 
               
               
                   
                   
                 TGGAGCCTCATTATGGAAAGTGTGGTCCCATCTGACAAGGGAAATTATACCTGTGTA 
               
               
                   
                   
                 GTGGAGAATGAATACGGGTCCATCAATCACACGTACCACCTGGATGTTGTGGAGCGA 
               
               
                   
                   
                 TCGCCTCACCGGCCCATCCTCCAAGCCGGACTGCCGGCAAATGCCTCCACAGTGGTC 
               
               
                   
                   
                 GGAGGAGACGTAGAGTTTGTCTGCAAGGTTTACAGTGATGCCCAGCCCCACATCCAG 
               
               
                   
                   
                 TGGATCAAGCACGTGGAAAAGAACGGCAGTAAATACGGGCCCGACGGGCTGCCCTAC 
               
               
                   
                   
                 CTCAAGGTTCTCAAGGCCGCCGGTGTTAACACCACGGACAAAGAGATTGAGGTTCTC 
               
               
                   
                   
                 TATATTCGGAATGTAACTTTTGAGGACGCTGGGGAATATACGTGCTTGGCGGGTAAT 
               
               
                   
                   
                 TCTATTGGGATATCCTTTCACTCTGCATGGTTGACAGTTCTGCCAGCGCCTGGAAGA 
               
               
                   
                   
                 GAAAAGGAGATTACAGCTTCCCCAGACTACCTGGAGATAGCCATTTACTGCATAGGG 
               
               
                   
                   
                 GTCTTCTTAATCGCCTGTATGGTGGTAACAGTCATCCTGTGCCGAATGAAGAACACG 
               
               
                   
                   
                 ACCAAGAAGCCAGACTTCAGCAGCCAGCCGGCTGTGCACAAGCTGACCAAACGTATC 
               
               
                   
                   
                 CCCCTGCGGAGACAGGTAACAGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAAC 
               
               
                   
                   
                 ACCCCGCTGGTGAGGATAACAACACGCCTCTCTTCAACGGCAGACACCCCCATGCTG 
               
               
                   
                   
                 GCAGGGGTCTCCGAGTATGAACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGAT 
               
               
                   
                   
                 AAGCTGACACTGGGCAAGCCCCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCG 
               
               
                   
                   
                 GAAGCAGTGGGAATTGACAAAGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAG 
               
               
                   
                   
                 ATGTTGAAAGATGATGCCACAGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAG 
               
               
                   
                   
                 ATGATGAAGATGATTGGGAAACACAAGAATATCATAAATCTTCTTGGAGCCTGCACA 
               
               
                   
                   
                 CAGGATGGGCCTCTCTATGTCATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAA 
               
               
                   
                   
                 TACCTCCGAGCCCGGAGGCCACCCGGGATGGAGTACTCCTATGACATTAACCGTGTT 
               
               
                   
                   
                 CCTGAGGAGCAGATGACCTTCAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGA 
               
               
                   
                   
                 GGCATGGAGTACTTGGCTTCCCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAAT 
               
               
                   
                   
                 GTTTTGGTAACAGAAAACAATGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGAT 
               
               
                   
                   
                 ATCAACAATATAGACTATTACAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGG 
               
               
                   
                   
                 ATGGCTCCAGAAGCCCTGTTTGATAGAGTATACACTCATCAGAGTGATGTCTGGTCC 
               
               
                   
                   
                 TTCGGGGTGTTAATGTGGGAGATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATT 
               
               
                   
                   
                 CCCGTGGAGGAACTTTTTAAGCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCC 
               
               
                   
                   
                 AACTGCACCAACGAACTGTACATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCC 
               
               
                   
                   
                 CAGAGACCAACGTTCAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACA 
               
               
                   
                   
                 ACCAATGAGGAATACTTGGACCTCAGCCAACCTCTCGAACAGTATTCACCTAGTTAC 
               
               
                   
                   
                 CCTGACACAAGAAGTTCTTGTTCTTCAGGAGATGATTCTGTTTTTTCTCCAGACCCC 
               
               
                   
                   
                 ATGCCTTACGAACCATGCCTTCCTCAGTATCCACACATAAACGGCAGTGTTAAAACA 
               
               
                   
                   
                 TGAATGACTGTGTCTGCCTGTCCCCAAACAGGACAGCACTGGGAACCTAGCTACACT 
               
               
                   
                   
                 GAGCAGGGAGACCATGCCTCCCAGAGCTTGTTGTCTCCACTTGTATATATGGATCAG 
               
               
                   
                   
                 AGGAGTAAATAATTGGAAAAGTAATCAGCATATGTGTAAAGATTTATACAGTTGAAA 
               
               
                   
                   
                 ACTTGTAATCTTCCCCAGGAGGAGAAGAAGGTTTCTGGAGCAGTGGACTGCCACAAG 
               
               
                   
                   
                 CCACCATGTAACCCCTCTCACCTGCCGTGCGTACTGGCTGTGGACCAGTAGGACTCA 
               
               
                   
                   
                 AGGTGGACGTGCGTTCTGCCTTCCTTGTTAATTTTGTAATAATTGGAGAAGATTTAT 
               
               
                   
                   
                 GTCAGCACACACTTACAGAGCACAAATGCAGTATATAGGTGCTGGATGTATGTAAAT 
               
               
                   
                   
                 ATATTCAAATTATGTATAAATATATATTATATATTTACAAGGAGTTATTTTTTGTAT 
               
               
                   
                   
                 TGATTTTAAATGGATGTCCCAATGCACCTAGAAAATTGGTCTCTCTTTTTTTAATAG 
               
               
                   
                   
                 CTATTTGCTAAATGCTGTTCTTACACATAATTTCTTAATTTTCACCGAGCAGAGGTG 
               
               
                   
                   
                 GAAAAATACTTTTGCTTTCAGGGAAAATGGTATAACGTTAATTTATTAATAAATTGG 
               
               
                   
                   
                 TAATATACAAAACAATTAATCATTTATAGTTTTTTTTGTAATTTAAGTGGCATTTCT 
               
               
                   
                   
                 ATGCAGGCAGCACAGCAGACTAGTTAATCTATTGCTTGGACTTAACTAGTTATCAGA 
               
               
                   
                   
                 TCCTTTGAAAAGAGAATATTTACAATATATGACTAATTTGGGGAAAATGAAGTTTTG 
               
               
                   
                   
                 ATTTATTTGTGTTTAAATGCTGCTGTCAGACGATTGTTCTTAGACCTCCTAAATGCC 
               
               
                   
                   
                 CCATATTAAAAGAACTCATTCATAGGAAGGTGTTTCATTTTGGTGTGCAACCCTGTC 
               
               
                   
                   
                 ATTACGTCAACGCAACGTCTAACTGGACTTCCCAAGATAAATGGTACCAGCGTCCTC 
               
               
                   
                   
                 TTAAAAGATGCCTTAATCCATTCCTTGAGGACAGACCTTAGTTGAAATGATAGCAGA 
               
               
                   
                   
                 ATGTGCTTCTCTCTGGCAGCTGGCCTTCTGCTTCTGAGTTGCACATTAATCAGATTA 
               
               
                   
                   
                 GCCTGTATTCTCTTCAGTGAATTTTGATAATGGCTTCCAGACTCTTTGGCGTTGGAG 
               
               
                   
                   
                 ACGCCTGTTAGGATCTTCAAGTCCCATCATAGAAAATTGAAACACAGAGTTGTTCTG 
               
               
                   
                   
                 CTGATAGTTTTGGGGATACGTCCATCTTTTTAAGGGATTGCTTTCATCTAATTCTGG 
               
               
                   
                   
                 CAGGACCTCACCAAAAGATCCAGCCTCATACCTACATCAGACAAAATATCGCCGTTG 
               
               
                   
                   
                 TTCCTTCTGTACTAAAGTATTGTGTTTTGCTTTGGAAACACCCACTCACTTTGCAAT 
               
               
                   
                   
                 AGCCGTGCAAGATGAATGCAGATTACACTGATCTTATGTGTTACAAAATTGGAGAAA 
               
               
                   
                   
                 GTATTTAATAAAACCTGTTAATTTTTATACTGACAATAAAAATGTTTCTACAGATAT 
               
               
                   
                   
                 TAATGTTAACAAGACAAAATAAATGTCACGCAACTTA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGES 
               
               
                 NO: 22 
                 isoform 2 
                 LEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVD 
               
               
                   
                 Amino acid 
                 SETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPA 
               
               
                   
                 sequence 
                 ANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGN 
               
               
                   
                   
                 YTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQ 
               
               
                   
                   
                 PHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTC 
               
               
                   
                   
                 LAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCR 
               
               
                   
                   
                 MKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTAD 
               
               
                   
                   
                 TPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVT 
               
               
                   
                   
                 VAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKG   
               
               
                   
                   
                   NLR EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDL 
               
               
                   
                   
                 AARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQS 
               
               
                   
                   
                 DVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWH 
               
               
                   
                   
                 AVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVF 
               
               
                   
                   
                 SPDPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 ACAGACTCTCCCGCAGAACTGACCCCAGCAAGAAGCCTTTGGGAGCAGTAGAGATGG 
               
               
                 NO: 23 
                 isoform 3 
                 AGTTTCACTATGTTGCCCAGGCTAGCCTTGAACTCCTGACCTCAGATGATCTGCCCG 
               
               
                   
                 Nucleic acid 
                 CGCAGGCCTCCCGAAGTGCTGGGATTACAGGCATGAGCCACCGCACCTGGCCTGCCA 
               
               
                   
                 sequence 
                 ACTCTTGTTAAGATCTCGAAGGAAACATTTTCTTCCCCTGAAGGAAACCCAGCTATG 
               
               
                   
                   
                 CAGACACCAGCTGATAATCTTGCATTCCTGAAAGATGTTGCACCCCTATGGCAAGTG 
               
               
                   
                   
                 GCGGCTGCTGAGGCTCTGACGTGACTCCCAGGCATGAACGCTCTCAGCTGTGTTTAC 
               
               
                   
                   
                 CTCAGCTCCTCGGGAGGGAGCCTGGGAGACTGACGCCTGAGTTTTACATCAGTGTCA 
               
               
                   
                   
                 AAACCCAAGCACAACCTAGGGAGGGACCTCCTGCCTAGTGTGTGTGGGTCAGGAGAT 
               
               
                   
                   
                 AGAAAAGCTCTCACTGAGTAAACTGGACAAGGTCAATATACCTCGCTGATTGAGAAG 
               
               
                   
                   
                 ACTTCACTCTCTCTGCAAAGAGACGTGTGTGTTTTAGAGGAAGTGGGAGCCCCAGCC 
               
               
                   
                   
                 GATTCTGCAAGACTTCCGAGAGTCAGATATCCAGACAGAAGATGCGGACACCTGGGT 
               
               
                   
                   
                 GACCAGACAGCGAAGAGGAAAGAACAAAACGAGCATGTGCCAAGCCTGTGAGGGAGA 
               
               
                   
                   
                 AAGGGCAACAAACCAGTGACCTTCCACAGAAATGTGTTTAAACAAAACAAAACAGCT 
               
               
                   
                   
                 CTTTGGCGTTGCTAAGAGACTGCCATTTTGGAGGAAAGAGCGATCGCCTCACCGGCC 
               
               
                   
                   
                 CATCCTCCAAGCCGGACTGCCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGA 
               
               
                   
                   
                 GTTTGTCTGCAAGGTTTACAGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGT 
               
               
                   
                   
                 GGAAAAGAACGGCAGTAAATACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAA 
               
               
                   
                   
                 GGCCGCCGGTGTTAACACCACGGACAAAGAGATTGAGGTTCTCTATATTCGGAATGT 
               
               
                   
                   
                 AACTTTTGAGGACGCTGGGGAATATACGTGCTTGGCGGGTAATTCTATTGGGATATC 
               
               
                   
                   
                 CTTTCACTCTGCATGGTTGACAGTTCTGCCAGCGCCTGGAAGAGAAAAGGAGATTAC 
               
               
                   
                   
                 AGCTTCCCCAGACTACCTGGAGATAGCCATTTACTGCATAGGGGTCTTCTTAATCGC 
               
               
                   
                   
                 CTGTATGGTGGTAACAGTCATCCTGTGCCGAATGAAGAACACGACCAAGAAGCCAGA 
               
               
                   
                   
                 CTTCAGCAGCCAGCCGGCTGTGCACAAGCTGACCAAACGTATCCCCCTGCGGAGACA 
               
               
                   
                   
                 GGTAACAGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAACACCCCGCTGGTGAG 
               
               
                   
                   
                 GATAACAACACGCCTCTCTTCAACGGCAGACACCCCCATGCTGGCAGGGGTCTCCGA 
               
               
                   
                   
                 GTATGAACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGATAAGCTGACACTGGG 
               
               
                   
                   
                 CAAGCCCCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCGGAAGCAGTGGGAAT 
               
               
                   
                   
                 TGACAAAGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAGATGTTGAAAGATGA 
               
               
                   
                   
                 TGCCACAGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAGATGATGAAGATGAT 
               
               
                   
                   
                 TGGGAAACACAAGAATATCATAAATCTTCTTGGAGCCTGCACACAGGATGGGCCTCT 
               
               
                   
                   
                 CTATGTCATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAATACCTCCGAGCCCG 
               
               
                   
                   
                 GAGGCCACCCGGGATGGAGTACTCCTATGACATTAACCGTGTTCCTGAGGAGCAGAT 
               
               
                   
                   
                 GACCTTCAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGAGGCATGGAGTACTT 
               
               
                   
                   
                 GGCTTCCCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAATGTTTTGGTAACAGA 
               
               
                   
                   
                 AAACAATGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGATATCAACAATATAGA 
               
               
                   
                   
                 CTATTACAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGGATGGCTCCAGAAGC 
               
               
                   
                   
                 CCTGTTTGATAGAGTATACACTCATCAGAGTGATGTCTGGTCCTTCGGGGTGTTAAT 
               
               
                   
                   
                 GTGGGAGATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATTCCCGTGGAGGAACT 
               
               
                   
                   
                 TTTTAAGCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCCAACTGCACCAACGA 
               
               
                   
                   
                 ACTGTACATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTT 
               
               
                   
                   
                 CAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACAACCAATGAGGAATA 
               
               
                   
                   
                 CTTGGACCTCAGCCAACCTCTCGAACAGTATTCACCTAGTTACCCTGACACAAGAAG 
               
               
                   
                   
                 TTCTTGTTCTTCAGGAGATGATTCTGTTTTTTCTCCAGACCCCATGCCTTACGAACC 
               
               
                   
                   
                 ATGCCTTCCTCAGTATCCACACATAAACGGCAGTGTTAAAACATGAATGACTGTGTC 
               
               
                   
                   
                 TGCCTGTCCCCAAACAGGACAGCACTGGGAACCTAGCTACACTGAGCAGGGAGACCA 
               
               
                   
                   
                 TGCCTCCCAGAGCTTGTTGTCTCCACTTGTATATATGGATCAGAGGAGTAAATAATT 
               
               
                   
                   
                 GGAAAAGTAATCAGCATATGTGTAAAGATTTATACAGTTGAAAACTTGTAATCTTCC 
               
               
                   
                   
                 CCAGGAGGAGAAGAAGGTTTCTGGAGCAGTGGACTGCCACAAGCCACCATGTAACCC 
               
               
                   
                   
                 CTCTCACCTGCCGTGCGTACTGGCTGTGGACCAGTAGGACTCAAGGTGGACGTGCGT 
               
               
                   
                   
                 TCTGCCTTCCTTGTTAATTTTGTAATAATTGGAGAAGATTTATGTCAGCACACACTT 
               
               
                   
                   
                 ACAGAGCACAAATGCAGTATATAGGTGCTGGATGTATGTAAATATATTCAAATTATG 
               
               
                   
                   
                 TATAAATATATATTATATATTTACAAGGAGTTATTTTTTGTATTGATTTTAAATGGA 
               
               
                   
                   
                 TGTCCCAATGCACCTAGAAAATTGGTCTCTCTTTTTTTAATAGCTATTTGCTAAATG 
               
               
                   
                   
                 CTGTTCTTACACATAATTTCTTAATTTTCACCGAGCAGAGGTGGAAAAATACTTTTG 
               
               
                   
                   
                 CTTTCAGGGAAAATGGTATAACGTTAATTTATTAATAAATTGGTAATATACAAAACA 
               
               
                   
                   
                 ATTAATCATTTATAGTTTTTTTTGTAATTTAAGTGGCATTTCTATGCAGGCAGCACA 
               
               
                   
                   
                 GCAGACTAGTTAATCTATTGCTTGGACTTAACTAGTTATCAGATCCTTTGAAAAGAG 
               
               
                   
                   
                 AATATTTACAATATATGACTAATTTGGGGAAAATGAAGTTTTGATTTATTTGTGTTT 
               
               
                   
                   
                 AAATGCTGCTGTCAGACGATTGTTCTTAGACCTCCTAAATGCCCCATATTAAAAGAA 
               
               
                   
                   
                 CTCATTCATAGGAAGGTGTTTCATTTTGGTGTGCAACCCTGTCATTACGTCAACGCA 
               
               
                   
                   
                 ACGTCTAACTGGACTTCCCAAGATAAATGGTACCAGCGTCCTCTTAAAAGATGCCTT 
               
               
                   
                   
                 AATCCATTCCTTGAGGACAGACCTTAGTTGAAATGATAGCAGAATGTGCTTCTCTCT 
               
               
                   
                   
                 GGCAGCTGGCCTTCTGCTTCTGAGTTGCACATTAATCAGATTAGCCTGTATTCTCTT 
               
               
                   
                   
                 CAGTGAATTTTGATAATGGCTTCCAGACTCTTTGGCGTTGGAGACGCCTGTTAGGAT 
               
               
                   
                   
                 CTTCAAGTCCCATCATAGAAAATTGAAACACAGAGTTGTTCTGCTGATAGTTTTGGG 
               
               
                   
                   
                 GATACGTCCATCTTTTTAAGGGATTGCTTTCATCTAATTCTGGCAGGACCTCACCAA 
               
               
                   
                   
                 AAGATCCAGCCTCATACCTACATCAGACAAAATATCGCCGTTGTTCCTTCTGTACTA 
               
               
                   
                   
                 AAGTATTGTGTTTTGCTTTGGAAACACCCACTCACTTTGCAATAGCCGTGCAAGATG 
               
               
                   
                   
                 AATGCAGATTACACTGATCTTATGTGTTACAAAATTGGAGAAAGTATTTAATAAAAC 
               
               
                   
                   
                 CTGTTAATTTTTATACTGACAATAAAAATGTTTCTACAGATATTAATGTTAACAAGA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MCLNKTKQLFGVAKRLPFWRKERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQ 
               
               
                 NO: 24 
                 isoform 3 
                 PHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTC 
               
               
                   
                 Amino acid 
                 LAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCR 
               
               
                   
                 sequence 
                 MKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTAD 
               
               
                   
                   
                 TPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVT 
               
               
                   
                   
                 VAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKG   
               
               
                   
                   
                   NLR EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDL 
               
               
                   
                   
                 AARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQS 
               
               
                   
                   
                 DVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWH 
               
               
                   
                   
                 AVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVF 
               
               
                   
                   
                 SPDPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 TGACTGCAGCAGCAGCGGCAGCGCCTCGGTTCCTGAGCCCACCGCAGGCTGAAGGCA 
               
               
                 NO: 25 
                 isoform 4 
                 TTGCGCGTAGTCCATGCCCGTAGAGGAAGTGTGCAGATGGGATTAACGTCCACATGG 
               
               
                   
                 Nucleic acid 
                 AGATATGGAAGAGGACCGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTC 
               
               
                   
                 sequence 
                 ATCTGCCTGGTCGTGGTCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGT 
               
               
                   
                   
                 TTAGTTGAGGATACCACATTAGAGCCAGAAGAGCCACCAACCAAATACCAAATCTCT 
               
               
                   
                   
                 CAACCAGAAGTGTACGTGGCTGCGCCAGGGGAGTCGCTAGAGGTGCGCTGCCTGTTG 
               
               
                   
                   
                 AAAGATGCCGCCGTGATCAGTTGGACTAAGGATGGGGTGCACTTGGGGCCCAACAAT 
               
               
                   
                   
                 AGGACAGTGCTTATTGGGGAGTACTTGCAGATAAAGGGCGCCACGCCTAGAGACTCC 
               
               
                   
                   
                 GGCCTCTATGCTTGTACTGCCAGTAGGACTGTAGACAGTGAAACTTGGTACTTCATG 
               
               
                   
                   
                 GTGAATGTCACAGATGCCATCTCATCCGGAGATGATGAGGATGACACCGATGGTGCG 
               
               
                   
                   
                 GAAGATTTTGTCAGTGAGAACAGTAACAACAAGAGAGCACCATACTGGACCAACACA 
               
               
                   
                   
                 GAAAAGATGGAAAAGCGGCTCCATGCTGTGCCTGCGGCCAACACTGTCAAGTTTCGC 
               
               
                   
                   
                 TGCCCAGCCGGGGGGAACCCAATGCCAACCATGCGGTGGCTGAAAAACGGGAAGGAG 
               
               
                   
                   
                 TTTAAGCAGGAGCATCGCATTGGAGGCTACAAGGTACGAAACCAGCACTGGAGCCTC 
               
               
                   
                   
                 ATTATGGAAAGTGTGGTCCCATCTGACAAGGGAAATTATACCTGTGTAGTGGAGAAT 
               
               
                   
                   
                 GAATACGGGTCCATCAATCACACGTACCACCTGGATGTTGTGGCGCCTGGAAGAGAA 
               
               
                   
                   
                 AAGGAGATTACAGCTTCCCCAGACTACCTGGAGATAGCCATTTACTGCATAGGGGTC 
               
               
                   
                   
                 TTCTTAATCGCCTGTATGGTGGTAACAGTCATCCTGTGCCGAATGAAGAACACGACC 
               
               
                   
                   
                 AAGAAGCCAGACTTCAGCAGCCAGCCGGCTGTGCACAAGCTGACCAAACGTATCCCC 
               
               
                   
                   
                 CTGCGGAGACAGGTAACAGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAACACC 
               
               
                   
                   
                 CCGCTGGTGAGGATAACAACACGCCTCTCTTCAACGGCAGACACCCCCATGCTGGCA 
               
               
                   
                   
                 GGGGTCTCCGAGTATGAACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGATAAG 
               
               
                   
                   
                 CTGACACTGGGCAAGCCCCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCGGAA 
               
               
                   
                   
                 GCAGTGGGAATTGACAAAGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAGATG 
               
               
                   
                   
                 TTGAAAGATGATGCCACAGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAGATG 
               
               
                   
                   
                 ATGAAGATGATTGGGAAACACAAGAATATCATAAATCTTCTTGGAGCCTGCACACAG 
               
               
                   
                   
                 GATGGGCCTCTCTATGTCATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAATAC 
               
               
                   
                   
                 CTCCGAGCCCGGAGGCCACCCGGGATGGAGTACTCCTATGACATTAACCGTGTTCCT 
               
               
                   
                   
                 GAGGAGCAGATGACCTTCAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGAGGC 
               
               
                   
                   
                 ATGGAGTACTTGGCTTCCCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAATGTT 
               
               
                   
                   
                 TTGGTAACAGAAAACAATGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGATATC 
               
               
                   
                   
                 AACAATATAGACTATTACAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGGATG 
               
               
                   
                   
                 GCTCCAGAAGCCCTGTTTGATAGAGTATACACTCATCAGAGTGATGTCTGGTCCTTC 
               
               
                   
                   
                 GGGGTGTTAATGTGGGAGATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATTCCC 
               
               
                   
                   
                 GTGGAGGAACTTTTTAAGCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCCAAC 
               
               
                   
                   
                 TGCACCAACGAACTGTACATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCCCAG 
               
               
                   
                   
                 AGACCAACGTTCAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACAACC 
               
               
                   
                   
                 AATGAGGAATACTTGGACCTCAGCCAACCTCTCGAACAGTATTCACCTAGTTACCCT 
               
               
                   
                   
                 GACACAAGAAGTTCTTGTTCTTCAGGAGATGATTCTGTTTTTTCTCCAGACCCCATG 
               
               
                   
                   
                 CCTTACGAACCATGCCTTCCTCAGTATCCACACATAAACGGCAGTGTTAAAACATGA 
               
               
                   
                   
                 ATGACTGTGTCTGCCTGTCCCCAAACAGGACAGCACTGGGAACCTAGCTACACTGAG 
               
               
                   
                   
                 CAGGGAGACCATGCCTCCCAGAGCTTGTTGTCTCCACTTGTATATATGGATCAGAGG 
               
               
                   
                   
                 AGTAAATAATTGGAAAAGTAATCAGCATATGTGTAAAGATTTATACAGTTGAAAACT 
               
               
                   
                   
                 TGTAATCTTCCCCAGGAGGAGAAGAAGGTTTCTGGAGCAGTGGACTGCCACAAGCCA 
               
               
                   
                   
                 CCATGTAACCCCTCTCACCTGCCGTGCGTACTGGCTGTGGACCAGTAGGACTCAAGG 
               
               
                   
                   
                 TGGACGTGCGTTCTGCCTTCCTTGTTAATTTTGTAATAATTGGAGAAGATTTATGTC 
               
               
                   
                   
                 AGCACACACTTACAGAGCACAAATGCAGTATATAGGTGCTGGATGTATGTAAATATA 
               
               
                   
                   
                 TTCAAATTATGTATAAATATATATTATATATTTACAAGGAGTTATTTTTTGTATTGA 
               
               
                   
                   
                 TTTTAAATGGATGTCCCAATGCACCTAGAAAATTGGTCTCTCTTTTTTTAATAGCTA 
               
               
                   
                   
                 TTTGCTAAATGCTGTTCTTACACATAATTTCTTAATTTTCACCGAGCAGAGGTGGAA 
               
               
                   
                   
                 AAATACTTTTGCTTTCAGGGAAAATGGTATAACGTTAATTTATTAATAAATTGGTAA 
               
               
                   
                   
                 TATACAAAACAATTAATCATTTATAGTTTTTTTTGTAATTTAAGTGGCATTTCTATG 
               
               
                   
                   
                 CAGGCAGCACAGCAGACTAGTTAATCTATTGCTTGGACTTAACTAGTTATCAGATCC 
               
               
                   
                   
                 TTTGAAAAGAGAATATTTACAATATATGACTAATTTGGGGAAAATGAAGTTTTGATT 
               
               
                   
                   
                 TATTTGTGTTTAAATGCTGCTGTCAGACGATTGTTCTTAGACCTCCTAAATGCCCCA 
               
               
                   
                   
                 TATTAAAAGAACTCATTCATAGGAAGGTGTTTCATTTTGGTGTGCAACCCTGTCATT 
               
               
                   
                   
                 ACGTCAACGCAACGTCTAACTGGACTTCCCAAGATAAATGGTACCAGCGTCCTCTTA 
               
               
                   
                   
                 AAAGATGCCTTAATCCATTCCTTGAGGACAGACCTTAGTTGAAATGATAGCAGAATG 
               
               
                   
                   
                 TGCTTCTCTCTGGCAGCTGGCCTTCTGCTTCTGAGTTGCACATTAATCAGATTAGCC 
               
               
                   
                   
                 TGTATTCTCTTCAGTGAATTTTGATAATGGCTTCCAGACTCTTTGGCGTTGGAGACG 
               
               
                   
                   
                 CCTGTTAGGATCTTCAAGTCCCATCATAGAAAATTGAAACACAGAGTTGTTCTGCTG 
               
               
                   
                   
                 ATAGTTTTGGGGATACGTCCATCTTTTTAAGGGATTGCTTTCATCTAATTCTGGCAG 
               
               
                   
                   
                 GACCTCACCAAAAGATCCAGCCTCATACCTACATCAGACAAAATATCGCCGTTGTTC 
               
               
                   
                   
                 CTTCTGTACTAAAGTATTGTGTTTTGCTTTGGAAACACCCACTCACTTTGCAATAGC 
               
               
                   
                   
                 CGTGCAAGATGAATGCAGATTACACTGATCTTATGTGTTACAAAATTGGAGAAAGTA 
               
               
                   
                   
                 TTTAATAAAACCTGTTAATTTTTATACTGACAATAAAAATGTTTCTACAGATATTAA 
               
               
                   
                   
                 TGTTAACAAGACAAAATAAATGTCACGCAACTTATTTTTTT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGES 
               
               
                 NO: 26 
                 isoform 4 
                 LEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVD 
               
               
                   
                 Amino acid 
                 SETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPA 
               
               
                   
                 sequence 
                 ANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGN 
               
               
                   
                   
                 YTCVVENEYGSINHTYHLDVVAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVIL 
               
               
                   
                   
                 CRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSST 
               
               
                   
                   
                 ADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEA 
               
               
                   
                   
                 VTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYAS   
               
               
                   
                   
                   KGNLR EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHR 
               
               
                   
                   
                 DLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTH 
               
               
                   
                   
                 QSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDC 
               
               
                   
                   
                 WHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDS 
               
               
                   
                   
                 VFSPDPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 AATTTGTTGAGGAATTTCCCCCTAGCCTTGACCCCTTGACAGCTCCCGCTCCTACTC 
               
               
                 NO: 27 
                 isoform 5 
                 AGTGCTGGGGAGAAGTAGGGAGGCCTTAAGCGAAGAGATGGGTCTGCACTTTGGAGG 
               
               
                   
                 Nucleic acid 
                 AGCCGGACACTGTTGACTTTCCTGATGTGAAATCTACCCAGGAACAAAACACCAGTG 
               
               
                   
                 sequence 
                 ACTGCAGCAGCAGCGGCAGCGCCTCGGTTCCTGAGCCCACCGCAGGCTGAAGGCATT 
               
               
                   
                   
                 GCGCGTAGTCCATGCCCGTAGAGGAAGTGTGCAGATGGGATTAACGTCCACATGGAG 
               
               
                   
                   
                 ATATGGAAGAGGACCGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTCAT 
               
               
                   
                   
                 CTGCCTGGTCGTGGTCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTT 
               
               
                   
                   
                 AGTTGAGGATACCACATTAGAGCCAGAAGATGCCATCTCATCCGGAGATGATGAGGA 
               
               
                   
                   
                 TGACACCGATGGTGCGGAAGATTTTGTCAGTGAGAACAGTAACAACAAGAGAGCACC 
               
               
                   
                   
                 ATACTGGACCAACACAGAAAAGATGGAAAAGCGGCTCCATGCTGTGCCTGCGGCCAA 
               
               
                   
                   
                 CACTGTCAAGTTTCGCTGCCCAGCCGGGGGGAACCCAATGCCAACCATGCGGTGGCT 
               
               
                   
                   
                 GAAAAACGGGAAGGAGTTTAAGCAGGAGCATCGCATTGGAGGCTACAAGGTACGAAA 
               
               
                   
                   
                 CCAGCACTGGAGCCTCATTATGGAAAGTGTGGTCCCATCTGACAAGGGAAATTATAC 
               
               
                   
                   
                 CTGTGTAGTGGAGAATGAATACGGGTCCATCAATCACACGTACCACCTGGATGTTGT 
               
               
                   
                   
                 GGAGCGATCGCCTCACCGGCCCATCCTCCAAGCCGGACTGCCGGCAAATGCCTCCAC 
               
               
                   
                   
                 AGTGGTCGGAGGAGACGTAGAGTTTGTCTGCAAGGTTTACAGTGATGCCCAGCCCCA 
               
               
                   
                   
                 CATCCAGTGGATCAAGCACGTGGAAAAGAACGGCAGTAAATACGGGCCCGACGGGCT 
               
               
                   
                   
                 GCCCTACCTCAAGGTTCTCAAGGCCGCCGGTGTTAACACCACGGACAAAGAGATTGA 
               
               
                   
                   
                 GGTTCTCTATATTCGGAATGTAACTTTTGAGGACGCTGGGGAATATACGTGCTTGGC 
               
               
                   
                   
                 GGGTAATTCTATTGGGATATCCTTTCACTCTGCATGGTTGACAGTTCTGCCAGCGCC 
               
               
                   
                   
                 TGGAAGAGAAAAGGAGATTACAGCTTCCCCAGACTACCTGGAGATAGCCATTTACTG 
               
               
                   
                   
                 CATAGGGGTCTTCTTAATCGCCTGTATGGTGGTAACAGTCATCCTGTGCCGAATGAA 
               
               
                   
                   
                 GAACACGACCAAGAAGCCAGACTTCAGCAGCCAGCCGGCTGTGCACAAGCTGACCAA 
               
               
                   
                   
                 ACGTATCCCCCTGCGGAGACAGGTAACAGTTTCGGCTGAGTCCAGCTCCTCCATGAA 
               
               
                   
                   
                 CTCCAACACCCCGCTGGTGAGGATAACAACACGCCTCTCTTCAACGGCAGACACCCC 
               
               
                   
                   
                 CATGCTGGCAGGGGTCTCCGAGTATGAACTTCCAGAGGACCCAAAATGGGAGTTTCC 
               
               
                   
                   
                 AAGAGATAAGCTGACACTGGGCAAGCCCCTGGGAGAAGGTTGCTTTGGGCAAGTGGT 
               
               
                   
                   
                 CATGGCGGAAGCAGTGGGAATTGACAAAGACAAGCCCAAGGAGGCGGTCACCGTGGC 
               
               
                   
                   
                 CGTGAAGATGTTGAAAGATGATGCCACAGAGAAAGACCTTTCTGATCTGGTGTCAGA 
               
               
                   
                   
                 GATGGAGATGATGAAGATGATTGGGAAACACAAGAATATCATAAATCTTCTTGGAGC 
               
               
                   
                   
                 CTGCACACAGGATGGGCCTCTCTATGTCATAGTTGAGTATGCCTCTAAAGGCAACCT 
               
               
                   
                   
                 CCGAGAATACCTCCGAGCCCGGAGGCCACCCGGGATGGAGTACTCCTATGACATTAA 
               
               
                   
                   
                 CCGTGTTCCTGAGGAGCAGATGACCTTCAAGGACTTGGTGTCATGCACCTACCAGCT 
               
               
                   
                   
                 GGCCAGAGGCATGGAGTACTTGGCTTCCCAAAAATGTATTCATCGAGATTTAGCAGC 
               
               
                   
                   
                 CAGAAATGTTTTGGTAACAGAAAACAATGTGATGAAAATAGCAGACTTTGGACTCGC 
               
               
                   
                   
                 CAGAGATATCAACAATATAGACTATTACAAAAAGACCACCAATGGGCGGCTTCCAGT 
               
               
                   
                   
                 CAAGTGGATGGCTCCAGAAGCCCTGTTTGATAGAGTATACACTCATCAGAGTGATGT 
               
               
                   
                   
                 CTGGTCCTTCGGGGTGTTAATGTGGGAGATCTTCACTTTAGGGGGCTCGCCCTACCC 
               
               
                   
                   
                 AGGGATTCCCGTGGAGGAACTTTTTAAGCTGCTGAAGGAAGGACACAGAATGGATAA 
               
               
                   
                   
                 GCCAGCCAACTGCACCAACGAACTGTACATGATGATGAGGGACTGTTGGCATGCAGT 
               
               
                   
                   
                 GCCCTCCCAGAGACCAACGTTCAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCAC 
               
               
                   
                   
                 TCTCACAACCAATGAGGAGGAGAAGAAGGTTTCTGGAGCAGTGGACTGCCACAAGCC 
               
               
                   
                   
                 ACCATGTAACCCCTCTCACCTGCCGTGCGTACTGGCTGTGGACCAGTAGGACTCAAG 
               
               
                   
                   
                 GTGGACGTGCGTTCTGCCTTCCTTGTTAATTTTGTAATAATTGGAGAAGATTTATGT 
               
               
                   
                   
                 CAGCACACACTTACAGAGCACAAATGCAGTATATAGGTGCTGGATGTATGTAAATAT 
               
               
                   
                   
                 ATTCAAATTATGTATAAATATATATTATATATTTACAAGGAGTTATTTTTTGTATTG 
               
               
                   
                   
                 ATTTTAAATGGATGTCCCAATGCACCTAGAAAATTGGTCTCTCTTTTTTTAATAGCT 
               
               
                   
                   
                 ATTTGCTAAATGCTGTTCTTACACATAATTTCTTAATTTTCACCGAGCAGAGGTGGA 
               
               
                   
                   
                 AAAATACTTTTGCTTTCAGGGAAAATGGTATAACGTTAATTTATTAATAAATTGGTA 
               
               
                   
                   
                 ATATACAAAACAATTAATCATTTATAGTTTTTTTTGTAATTTAAGTGGCATTTCTAT 
               
               
                   
                   
                 GCAGGCAGCACAGCAGACTAGTTAATCTATTGCTTGGACTTAACTAGTTATCAGATC 
               
               
                   
                   
                 CTTTGAAAAGAGAATATTTACAATATATGACTAATTTGGGGAAAATGAAGTTTTGAT 
               
               
                   
                   
                 TTATTTGTGTTTAAATGCTGCTGTCAGACGATTGTTCTTAGACCTCCTAAATGCCCC 
               
               
                   
                   
                 ATATTAAAAGAACTCATTCATAGGAAGGTGTTTCATTTTGGTGTGCAACCCTGTCAT 
               
               
                   
                   
                 TACGTCAACGCAACGTCTAACTGGACTTCCCAAGATAAATGGTACCAGCGTCCTCTT 
               
               
                   
                   
                 AAAAGATGCCTTAATCCATTCCTTGAGGACAGACCTTAGTTGAAATGATAGCAGAAT 
               
               
                   
                   
                 GTGCTTCTCTCTGGCAGCTGGCCTTCTGCTTCTGAGTTGCACATTAATCAGATTAGC 
               
               
                   
                   
                 CTGTATTCTCTTCAGTGAATTTTGATAATGGCTTCCAGACTCTTTGGCGTTGGAGAC 
               
               
                   
                   
                 GCCTGTTAGGATCTTCAAGTCCCATCATAGAAAATTGAAACACAGAGTTGTTCTGCT 
               
               
                   
                   
                 GATAGTTTTGGGGATACGTCCATCTTTTTAAGGGATTGCTTTCATCTAATTCTGGCA 
               
               
                   
                   
                 GGACCTCACCAAAAGATCCAGCCTCATACCTACATCAGACAAAATATCGCCGTTGTT 
               
               
                   
                   
                 CCTTCTGTACTAAAGTATTGTGTTTTGCTTTGGAAACACCCACTCACTTTGCAATAG 
               
               
                   
                   
                 CCGTGCAAGATGAATGCAGATTACACTGATCTTATGTGTTACAAAATTGGAGAAAGT 
               
               
                   
                   
                 ATTTAATAAAACCTGTTAATTTTTATACTGACAATAAAAATGTTTCTACAGATATTA 
               
               
                   
                   
                 ATGTTAACAAGACAAAATAAATGTCACGCAACTTATTTTTTT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEDAISSGDDEDDTDGAEDFVSE 
               
               
                 NO. 28 
                 isoform 5 
                 NSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHR 
               
               
                   
                 Amino acid 
                 IGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQA 
               
               
                   
                 sequence 
                 GLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGV 
               
               
                   
                   
                 NTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLPAPGREKEITASPD 
               
               
                   
                   
                 YLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVS 
               
               
                   
                   
                 AESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLG 
               
               
                   
                   
                 EGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHK 
               
               
                   
                   
                 NIINLLGACTQDGPLYV IVEYASKGNLR EYLRARRPPGMEYSYDINRVPEEQMTFKD 
               
               
                   
                   
                 LVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKK 
               
               
                   
                   
                 TTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLL 
               
               
                   
                   
                 KEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEEKKVS 
               
               
                   
                   
                 GAVDCHKPPCNPSHLPCVLAVDQ 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 GGCGGCGGCTGGAGGAGAGCGCGGTGGAGAGCCGAGCGGGCGGGCGGCGGGTGCGGA 
               
               
                 NO. 29 
                 isoform 6 
                 GCGGGCGAGGGAGCGCGCGCGGCCGCCACAAAGCTCGGGCGCCGCGGGGCTGCATGC 
               
               
                   
                 Nucleic acid 
                 GGCGTACCTGGCCCGGCGCGGCGACTGCTCTCCGGGCTGGCGGGGGCCGGCCGCGAG 
               
               
                   
                 sequence 
                 CCCCGGGGGCCCCGAGGCCGCAGCTTGCCTGCGCGCTCTGAGCCTTCGCAACTCGCG 
               
               
                   
                   
                 AGCAAAGTTTGGTGGAGGCAACGCCAAGCCTGAGTCCTTTCTTCCTCTCGTTCCCCA 
               
               
                   
                   
                 AATCCGAGGGCAGCCCGCGGGCGTCATGCCCGCGCTCCTCCGCAGCCTGGGGTACGC 
               
               
                   
                   
                 GTGAAGCCCGGGAGGCTTGGCGCCGGCGAAGACCCAAGGACCACTCTTCTGCGTTTG 
               
               
                   
                   
                 GAGTTGCTCCCCGCAACCCCGGGCTCGTCGCTTTCTCCATCCCGACCCACGCGGGGC 
               
               
                   
                   
                 GCGGGGACAACACAGGTCGCGGAGGAGCGTTGCCATTCAAGTGACTGCAGCAGCAGC 
               
               
                   
                   
                 GGCAGCGCCTCGGTTCCTGAGCCCACCGCAGGCTGAAGGCATTGCGCGTAGTCCATG 
               
               
                   
                   
                 CCCGTAGAGGAAGTGTGCAGATGGGATTAACGTCCACATGGAGATATGGAAGAGGAC 
               
               
                   
                   
                 CGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTCATCTGCCTGGTCGTGG 
               
               
                   
                   
                 TCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTTAGTTGAGGATACCA 
               
               
                   
                   
                 CATTAGAGCCAGAAGGAGCACCATACTGGACCAACACAGAAAAGATGGAAAAGCGGC 
               
               
                   
                   
                 TCCATGCTGTGCCTGCGGCCAACACTGTCAAGTTTCGCTGCCCAGCCGGGGGGAACC 
               
               
                   
                   
                 CAATGCCAACCATGCGGTGGCTGAAAAACGGGAAGGAGTTTAAGCAGGAGCATCGCA 
               
               
                   
                   
                 TTGGAGGCTACAAGGTACGAAACCAGCACTGGAGCCTCATTATGGAAAGTGTGGTCC 
               
               
                   
                   
                 CATCTGACAAGGGAAATTATACCTGTGTAGTGGAGAATGAATACGGGTCCATCAATC 
               
               
                   
                   
                 ACACGTACCACCTGGATGTTGTGGAGCGATCGCCTCACCGGCCCATCCTCCAAGCCG 
               
               
                   
                   
                 GACTGCCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGAGTTTGTCTGCAAGG 
               
               
                   
                   
                 TTTACAGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGTGGAAAAGAACGGCA 
               
               
                   
                   
                 GTAAATACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAAGGCCGCCGGTGTTA 
               
               
                   
                   
                 ACACCACGGACAAAGAGATTGAGGTTCTCTATATTCGGAATGTAACTTTTGAGGACG 
               
               
                   
                   
                 CTGGGGAATATACGTGCTTGGCGGGTAATTCTATTGGGATATCCTTTCACTCTGCAT 
               
               
                   
                   
                 GGTTGACAGTTCTGCCAGCGCCTGGAAGAGAAAAGGAGATTACAGCTTCCCCAGACT 
               
               
                   
                   
                 ACCTGGAGATAGCCATTTACTGCATAGGGGTCTTCTTAATCGCCTGTATGGTGGTAA 
               
               
                   
                   
                 CAGTCATCCTGTGCCGAATGAAGAACACGACCAAGAAGCCAGACTTCAGCAGCCAGC 
               
               
                   
                   
                 CGGCTGTGCACAAGCTGACCAAACGTATCCCCCTGCGGAGACAGGTTTCGGCTGAGT 
               
               
                   
                   
                 CCAGCTCCTCCATGAACTCCAACACCCCGCTGGTGAGGATAACAACACGCCTCTCTT 
               
               
                   
                   
                 CAACGGCAGACACCCCCATGCTGGCAGGGGTCTCCGAGTATGAACTTCCAGAGGACC 
               
               
                   
                   
                 CAAAATGGGAGTTTCCAAGAGATAAGCTGACACTGGGCAAGCCCCTGGGAGAAGGTT 
               
               
                   
                   
                 GCTTTGGGCAAGTGGTCATGGCGGAAGCAGTGGGAATTGACAAAGACAAGCCCAAGG 
               
               
                   
                   
                 AGGCGGTCACCGTGGCCGTGAAGATGTTGAAAGATGATGCCACAGAGAAAGACCTTT 
               
               
                   
                   
                 CTGATCTGGTGTCAGAGATGGAGATGATGAAGATGATTGGGAAACACAAGAATATCA 
               
               
                   
                   
                 TAAATCTTCTTGGAGCCTGCACACAGGATGGGCCTCTCTATGTCATAGTTGAGTATG 
               
               
                   
                   
                 CCTCTAAAGGCAACCTCCGAGAATACCTCCGAGCCCGGAGGCCACCCGGGATGGAGT 
               
               
                   
                   
                 ACTCCTATGACATTAACCGTGTTCCTGAGGAGCAGATGACCTTCAAGGACTTGGTGT 
               
               
                   
                   
                 CATGCACCTACCAGCTGGCCAGAGGCATGGAGTACTTGGCTTCCCAAAAATGTATTC 
               
               
                   
                   
                 ATCGAGATTTAGCAGCCAGAAATGTTTTGGTAACAGAAAACAATGTGATGAAAATAG 
               
               
                   
                   
                 CAGACTTTGGACTCGCCAGAGATATCAACAATATAGACTATTACAAAAAGACCACCA 
               
               
                   
                   
                 ATGGGCGGCTTCCAGTCAAGTGGATGGCTCCAGAAGCCCTGTTTGATAGAGTATACA 
               
               
                   
                   
                 CTCATCAGAGTGATGTCTGGTCCTTCGGGGTGTTAATGTGGGAGATCTTCACTTTAG 
               
               
                   
                   
                 GGGGCTCGCCCTACCCAGGGATTCCCGTGGAGGAACTTTTTAAGCTGCTGAAGGAAG 
               
               
                   
                   
                 GACACAGAATGGATAAGCCAGCCAACTGCACCAACGAACTGTACATGATGATGAGGG 
               
               
                   
                   
                 ACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAGCAGTTGGTAGAAGACT 
               
               
                   
                   
                 TGGATCGAATTCTCACTCTCACAACCAATGAGGAATACTTGGACCTCAGCCAACCTC 
               
               
                   
                   
                 TCGAACAGTATTCACCTAGTTACCCTGACACAAGAAGTTCTTGTTCTTCAGGAGATG 
               
               
                   
                   
                 ATTCTGTTTTTTCTCCAGACCCCATGCCTTACGAACCATGCCTTCCTCAGTATCCAC 
               
               
                   
                   
                 ACATAAACGGCAGTGTTAAAACATGAATGACTGTGTCTGCCTGTCCCCAAACAGGAC 
               
               
                   
                   
                 AGCACTGGGAACCTAGCTACACTGAGCAGGGAGACCATGCCTCCCAGAGCTTGTTGT 
               
               
                   
                   
                 CTCCACTTGTATATATGGATCAGAGGAGTAAATAATTGGAAAAGTAATCAGCATATG 
               
               
                   
                   
                 TGTAAAGATTTATACAGTTGAAAACTTGTAATCTTCCCCAGGAGGAGAAGAAGGTTT 
               
               
                   
                   
                 CTGGAGCAGTGGACTGCCACAAGCCACCATGTAACCCCTCTCACCTGCCGTGCGTAC 
               
               
                   
                   
                 TGGCTGTGGACCAGTAGGACTCAAGGTGGACGTGCGTTCTGCCTTCCTTGTTAATTT 
               
               
                   
                   
                 TGTAATAATTGGAGAAGATTTATGTCAGCACACACTTACAGAGCACAAATGCAGTAT 
               
               
                   
                   
                 ATAGGTGCTGGATGTATGTAAATATATTCAAATTATGTATAAATATATATTATATAT 
               
               
                   
                   
                 TTACAAGGAGTTATTTTTTGTATTGATTTTAAATGGATGTCCCAATGCACCTAGAAA 
               
               
                   
                   
                 ATTGGTCTCTCTTTTTTTAATAGCTATTTGCTAAATGCTGTTCTTACACATAATTTC 
               
               
                   
                   
                 TTAATTTTCACCGAGCAGAGGTGGAAAAATACTTTTGCTTTCAGGGAAAATGGTATA 
               
               
                   
                   
                 ACGTTAATTTATTAATAAATTGGTAATATACAAAACAATTAATCATTTATAGTTTTT 
               
               
                   
                   
                 TTTGTAATTTAAGTGGCATTTCTATGCAGGCAGCACAGCAGACTAGTTAATCTATTG 
               
               
                   
                   
                 CTTGGACTTAACTAGTTATCAGATCCTTTGAAAAGAGAATATTTACAATATATGACT 
               
               
                   
                   
                 AATTTGGGGAAAA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEGAPYWTNTEKMEKRLHAVPAA 
               
               
                 NO: 30 
                 isoform 6 
                 NTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNY 
               
               
                   
                 Amino acid 
                 TCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQP 
               
               
                   
                 sequence 
                 HIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCL 
               
               
                   
                   
                 AGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRM 
               
               
                   
                   
                 KNTTKKPDFSSQPAVHKLTKRIPLRRQVSAESSSSMNSNTPLVRITTRLSSTADTPM 
               
               
                   
                   
                 LAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAV 
               
               
                   
                   
                 KMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNLR   
               
               
                   
                   
                 EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAAR 
               
               
                   
                   
                 NVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVW 
               
               
                   
                   
                 SFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVP 
               
               
                   
                   
                 SQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPD 
               
               
                   
                   
                 PMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 CCGGCCGCGAGCCCCGGGGGCCCCGAGGCCGCAGCTTGCCTGCGCGCTCTGAGCCTT 
               
               
                 NO: 31 
                 isoform 7 
                 CGCAACTCGCGAGCAAAGTTTGGTGGAGGCAACGCCAAGCCTGAGTCCTTTCTTCCT 
               
               
                   
                 Nucleic acid 
                 CTCGTTCCCCAAATCCGAGGGCAGCCCGCGGGCGTCATGCCCGCGCTCCTCCGCAGC 
               
               
                   
                 sequence 
                 CTGGGGTACGCGTGAAGCCCGGGAGGCTTGGCGCCGGCGAAGACCCAAGGACCACTC 
               
               
                   
                   
                 TTCTGCGTTTGGAGTTGCTCCCCGCAACCCCGGGCTCGTCGCTTTCTCCATCCCGAC 
               
               
                   
                   
                 CCACGCGGGGCGCGGGGACAACACAGGTCGCGGAGGAGCGTTGCCATTCAAGTGACT 
               
               
                   
                   
                 GCAGCAGCAGCGGCAGCGCCTCGGTTCCTGAGCCCACCGCAGGCTGAAGGCATTGCG 
               
               
                   
                   
                 CGTAGTCCATGCCCGTAGAGGAAGTGTGCAGATGGGATTAACGTCCACATGGAGATA 
               
               
                   
                   
                 TGGAAGAGGACCGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTCATCTG 
               
               
                   
                   
                 CCTGGTCGTGGTCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTTAGT 
               
               
                   
                   
                 TGAGGATACCACATTAGAGCCAGAAGAGCCACCAACCAAATACCAAATCTCTCAACC 
               
               
                   
                   
                 AGAAGTGTACGTGGCTGCGCCAGGGGAGTCGCTAGAGGTGCGCTGCCTGTTGAAAGA 
               
               
                   
                   
                 TGCCGCCGTGATCAGTTGGACTAAGGATGGGGTGCACTTGGGGCCCAACAATAGGAC 
               
               
                   
                   
                 AGTGCTTATTGGGGAGTACTTGCAGATAAAGGGCGCCACGCCTAGAGACTCCGGCCT 
               
               
                   
                   
                 CTATGCTTGTACTGCCAGTAGGACTGTAGACAGTGAAACTTGGTACTTCATGGTGAA 
               
               
                   
                   
                 TGTCACAGATGCCATCTCATCCGGAGATGATGAGGATGACACCGATGGTGCGGAAGA 
               
               
                   
                   
                 TTTTGTCAGTGAGAACAGTAACAACAAGAGAGCACCATACTGGACCAACACAGAAAA 
               
               
                   
                   
                 GATGGAAAAGCGGCTCCATGCTGTGCCTGCGGCCAACACTGTCAAGTTTCGCTGCCC 
               
               
                   
                   
                 AGCCGGGGGGAACCCAATGCCAACCATGCGGTGGCTGAAAAACGGGAAGGAGTTTAA 
               
               
                   
                   
                 GCAGGAGCATCGCATTGGAGGCTACAAGGTACGAAACCAGCACTGGAGCCTCATTAT 
               
               
                   
                   
                 GGAAAGTGTGGTCCCATCTGACAAGGGAAATTATACCTGTGTAGTGGAGAATGAATA 
               
               
                   
                   
                 CGGGTCCATCAATCACACGTACCACCTGGATGTTGTGGAGCGATCGCCTCACCGGCC 
               
               
                   
                   
                 CATCCTCCAAGCCGGACTGCCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGA 
               
               
                   
                   
                 GTTTGTCTGCAAGGTTTACAGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGT 
               
               
                   
                   
                 GGAAAAGAACGGCAGTAAATACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAA 
               
               
                   
                   
                 GGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAACACCCCGCTGGTGAGGATAAC 
               
               
                   
                   
                 AACACGCCTCTCTTCAACGGCAGACACCCCCATGCTGGCAGGGGTCTCCGAGTATGA 
               
               
                   
                   
                 ACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGATAAGCTGACACTGGGCAAGCC 
               
               
                   
                   
                 CCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCGGAAGCAGTGGGAATTGACAA 
               
               
                   
                   
                 AGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAGATGTTGAAAGATGATGCCAC 
               
               
                   
                   
                 AGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAGATGATGAAGATGATTGGGAA 
               
               
                   
                   
                 ACACAAGAATATCATAAATCTTCTTGGAGCCTGCACACAGGATGGGCCTCTCTATGT 
               
               
                   
                   
                 CATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAATACCTCCGAGCCCGGAGGCC 
               
               
                   
                   
                 ACCCGGGATGGAGTACTCCTATGACATTAACCGTGTTCCTGAGGAGCAGATGACCTT 
               
               
                   
                   
                 CAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGAGGCATGGAGTACTTGGCTTC 
               
               
                   
                   
                 CCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAATGTTTTGGTAACAGAAAACAA 
               
               
                   
                   
                 TGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGATATCAACAATATAGACTATTA 
               
               
                   
                   
                 CAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGGATGGCTCCAGAAGCCCTGTT 
               
               
                   
                   
                 TGATAGAGTATACACTCATCAGAGTGATGTCTGGTCCTTCGGGGTGTTAATGTGGGA 
               
               
                   
                   
                 GATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATTCCCGTGGAGGAACTTTTTAA 
               
               
                   
                   
                 GCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCCAACTGCACCAACGAACTGTA 
               
               
                   
                   
                 CATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAGCA 
               
               
                   
                   
                 GTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACAACCAATGAGGAATACTTGGA 
               
               
                   
                   
                 CCTCAGCCAACCTCTCGAACAGTATTCACCTAGTTACCCTGACACAAGAAGTTCTTG 
               
               
                   
                   
                 TTCTTCAGGAGATGATTCTGTTTTTTCTCCAGACCCCATGCCTTACGAACCATGCCT 
               
               
                   
                   
                 TCCTCAGTATCCACACATAAACGGCAGTGTTAAAACATGAATGACTGTGTCTGCCTG 
               
               
                   
                   
                 TCCCCAAACAGGACAGCACTGGGAACCTAGCTACACTGAGCAGGGAGACCATGCCTC 
               
               
                   
                   
                 CCAGAGCTTGTTGTCTCCACTTGTATATATGGATCAGAGGAGTAAATAATTGGAAAA 
               
               
                   
                   
                 GTAATCAGCATATGTGTAAAGATTTATACAGTTGAAAACTTGTAATCTTCCCCAGGA 
               
               
                   
                   
                 GGAGAAGAAGGTTTCTGGAGCAGTGGACTGCCACAAGCCACCATGTAACCCCTCTCA 
               
               
                   
                   
                 CCTGCCGTGCGTACTGGCTGTGGACCAGTAGGACTCAAGGTGGACGTGCGTTCTGCC 
               
               
                   
                   
                 TTCCTTGTTAATTTTGTAATAATTGGAGAAGATTTATGTCAGCACACACTTACAGAG 
               
               
                   
                   
                 CACAAATGCAGTATATAGGTGCTGGATGTATGTAAATATATTCAAATTATGTATAAA 
               
               
                   
                   
                 TATATATTATATATTTACAAGGAGTTATTTTTTGTATTGATTTTAAATGGATGTCCC 
               
               
                   
                   
                 AATGCACCTAGAAAATTGGTCTCTCTTTTTTTAATAGCTATTTGCTAAATGCTGTTC 
               
               
                   
                   
                 TTACACATAATTTCTTAATTTTCACCGAGCAGAGGTGGAAAAATACTTTTGCTTTCA 
               
               
                   
                   
                 GGGAAAATGGTATAACGTTAATTTATTAATAAATTGGTAATATACAAAACAA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGES 
               
               
                 NO: 32 
                 isoform 7 
                 LEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVD 
               
               
                   
                 Amino acid 
                 SETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPA 
               
               
                   
                 sequence 
                 ANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGN 
               
               
                   
                   
                 YTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQ 
               
               
                   
                   
                 PHIQWIKHVEKNGSKYGPDGLPYLKVLKVSAESSSSMNSNTPLVRITTRLSSTADTP 
               
               
                   
                   
                 MLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVA 
               
               
                   
                   
                 VKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNL   
               
               
                   
                   
                   R EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAA 
               
               
                   
                   
                 RNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDV 
               
               
                   
                   
                 WSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAV 
               
               
                   
                   
                 PSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSP 
               
               
                   
                   
                 DPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 GAGCGGGCGAGGGAGCGCGCGCGGCCGCCACAAAGCTCGGGCGCCGCGGGGCTGCAT 
               
               
                 NO: 33 
                 isoform 8 
                 GCGGCGTACCTGGCCCGGCGCGGCGACTGCTCTCCGGGCTGGCGGGGGCCGGCCGCG 
               
               
                   
                 Nucleic acid 
                 AGCCCCGGGGGCCCCGAGGCCGCAGCTTGCCTGCGCGCTCTGAGCCTTCGCAACTCG 
               
               
                   
                 sequence 
                 CGAGCAAAGTTTGGTGGAGGCAACGCCAAGCCTGAGTCCTTTCTTCCTCTCGTTCCC 
               
               
                   
                   
                 CAAATCCGAGGGCAGCCCGCGGGCGTCATGCCCGCGCTCCTCCGCAGCCTGGGGTAC 
               
               
                   
                   
                 GCGTGAAGCCCGGGAGGCTTGGCGCCGGCGAAGACCCAAGGACCACTCTTCTGCGTT 
               
               
                   
                   
                 TGGAGTTGCTCCCCGCAACCCCGGGCTCGTCGCTTTCTCCATCCCGACCCACGCGGG 
               
               
                   
                   
                 GCGCGGGGACAACACAGGTCGCGGAGGAGCGTTGCCATTCAAGTGACTGCAGCAGCA 
               
               
                   
                   
                 GCGGCAGCGCCTCGGTTCCTGAGCCCACCGCAGGCTGAAGGCATTGCGCGTAGTCCA 
               
               
                   
                   
                 TGCCCGTAGAGGAAGTGTGCAGATGGGATTAACGTCCACATGGAGATATGGAAGAGG 
               
               
                   
                   
                 ACCGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTCATCTGCCTGGTCGT 
               
               
                   
                   
                 GGTCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTTAGTTGAGGATAC 
               
               
                   
                   
                 CACATTAGAGCCAGAAGAGCCACCAACCAAATACCAAATCTCTCAACCAGAAGTGTA 
               
               
                   
                   
                 CGTGGCTGCGCCAGGGGAGTCGCTAGAGGTGCGCTGCCTGTTGAAAGATGCCGCCGT 
               
               
                   
                   
                 GATCAGTTGGACTAAGGATGGGGTGCACTTGGGGCCCAACAATAGGACAGTGCTTAT 
               
               
                   
                   
                 TGGGGAGTACTTGCAGATAAAGGGCGCCACGCCTAGAGACTCCGGCCTCTATGCTTG 
               
               
                   
                   
                 TACTGCCAGTAGGACTGTAGACAGTGAAACTTGGTACTTCATGGTGAATGTCACAGA 
               
               
                   
                   
                 TGCCATCTCATCCGGAGATGATGAGGATGACACCGATGGTGCGGAAGATTTTGTCAG 
               
               
                   
                   
                 TGAGAACAGTAACAACAAGAGAGCACCATACTGGACCAACACAGAAAAGATGGAAAA 
               
               
                   
                   
                 GCGGCTCCATGCTGTGCCTGCGGCCAACACTGTCAAGTTTCGCTGCCCAGCCGGGGG 
               
               
                   
                   
                 GAACCCAATGCCAACCATGCGGTGGCTGAAAAACGGGAAGGAGTTTAAGCAGGAGCA 
               
               
                   
                   
                 TCGCATTGGAGGCTACAAGGTACGAAACCAGCACTGGAGCCTCATTATGGAAAGTGT 
               
               
                   
                   
                 GGTCCCATCTGACAAGGGAAATTATACCTGTGTAGTGGAGAATGAATACGGGTCCAT 
               
               
                   
                   
                 CAATCACACGTACCACCTGGATGTTGTGGAGCGATCGCCTCACCGGCCCATCCTCCA 
               
               
                   
                   
                 AGCCGGACTGCCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGAGTTTGTCTG 
               
               
                   
                   
                 CAAGGTTTACAGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGTGGAAAAGAA 
               
               
                   
                   
                 CGGCAGTAAATACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAAGCACTCGGG 
               
               
                   
                   
                 GATAAATAGTTCCAATGCAGAAGTGCTGGCTCTGTTCAATGTGACCGAGGCGGATGC 
               
               
                   
                   
                 TGGGGAATATATATGTAAGGTCTCCAATTATATAGGGCAGGCCAACCAGTCTGCCTG 
               
               
                   
                   
                 GCTCACTGTCCTGCCAAAACAGCAAGCGCCTGGAAGAGAAAAGGAGATTACAGCTTC 
               
               
                   
                   
                 CCCAGACTACCTGGAGATAGCCATTTACTGCATAGGGGTCTTCTTAATCGCCTGTAT 
               
               
                   
                   
                 GGTGGTAACAGTCATCCTGTGCCGAATGAAGAACACGACCAAGAAGCCAGACTTCAG 
               
               
                   
                   
                 CAGCCAGCCGGCTGTGCACAAGCTGACCAAACGTATCCCCCTGCGGAGACAGGTAAC 
               
               
                   
                   
                 AGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAACACCCCGCTGGTGAGGATAAC 
               
               
                   
                   
                 AACACGCCTCTCTTCAACGGCAGACACCCCCATGCTGGCAGGGGTCTCCGAGTATGA 
               
               
                   
                   
                 ACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGATAAGCTGACACTGGGCAAGCC 
               
               
                   
                   
                 CCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCGGAAGCAGTGGGAATTGACAA 
               
               
                   
                   
                 AGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAGATGTTGAAAGATGATGCCAC 
               
               
                   
                   
                 AGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAGATGATGAAGATGATTGGGAA 
               
               
                   
                   
                 ACACAAGAATATCATAAATCTTCTTGGAGCCTGCACACAGGATGGGCCTCTCTATGT 
               
               
                   
                   
                 CATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAATACCTCCGAGCCCGGAGGCC 
               
               
                   
                   
                 ACCCGGGATGGAGTACTCCTATGACATTAACCGTGTTCCTGAGGAGCAGATGACCTT 
               
               
                   
                   
                 CAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGAGGCATGGAGTACTTGGCTTC 
               
               
                   
                   
                 CCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAATGTTTTGGTAACAGAAAACAA 
               
               
                   
                   
                 TGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGATATCAACAATATAGACTATTA 
               
               
                   
                   
                 CAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGGATGGCTCCAGAAGCCCTGTT 
               
               
                   
                   
                 TGATAGAGTATACACTCATCAGAGTGATGTCTGGTCCTTCGGGGTGTTAATGTGGGA 
               
               
                   
                   
                 GATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATTCCCGTGGAGGAACTTTTTAA 
               
               
                   
                   
                 GCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCCAACTGCACCAACGAACTGTA 
               
               
                   
                   
                 CATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAGCA 
               
               
                   
                   
                 GTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACAACCAATGAGGAATACTTGGA 
               
               
                   
                   
                 CCTCAGCCAACCTCTCGAACAGTATTCACCTAGTTACCCTGACACAAGAAGTTCTTG 
               
               
                   
                   
                 TTCTTCAGGAGATGATTCTGTTTTTTCTCCAGACCCCATGCCTTACGAACCATGCCT 
               
               
                   
                   
                 TCCTCAGTATCCACACATAAACGGCAGTGTTAAAACATGA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGES 
               
               
                 NO: 34 
                 isoform 8 
                 LEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVD 
               
               
                   
                 Amino acid 
                 SETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPA 
               
               
                   
                 sequence 
                 ANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGN 
               
               
                   
                   
                 YTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQ 
               
               
                   
                   
                 PHIQWIKHVEKNGSKYGPDGLPYLKVLKHSGINSSNAEVLALFNVTEADAGEYICKV 
               
               
                   
                   
                 SNYIGQANQSAWLTVLPKQQAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILC 
               
               
                   
                   
                 RMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTA 
               
               
                   
                   
                 DTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAV 
               
               
                   
                   
                 TVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASK   
               
               
                   
                   
                   GNLR EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRD 
               
               
                   
                   
                 LAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQ 
               
               
                   
                   
                 SDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCW 
               
               
                   
                   
                 HAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSV 
               
               
                   
                   
                 FSPDPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 GAGAGCCGAGCGGGCGGGCGGCGGGTGCGGAGCGGGCGAGGGAGCGCGCGCGGCCGC 
               
               
                 NO: 35 
                 isoform 9 
                 CACAAAGCTCGGGCGCCGCGGGGCTGCATGCGGCGTACCTGGCCCGGCGCGGCGACT 
               
               
                   
                 Nucleic acid 
                 GCTCTCCGGGCTGGCGGGGGCCGGCCGCGAGCCCCGGGGGCCCCGAGGCCGCAGCTT 
               
               
                   
                 sequence 
                 GCCTGCGCGCTCTGAGCCTTCGCAACTCGCGAGCAAAGTTTGGTGGAGGCAACGCCA 
               
               
                   
                   
                 AGCCTGAGTCCTTTCTTCCTCTCGTTCCCCAAATCCGAGGGCAGCCCGCGGGCGTCA 
               
               
                   
                   
                 TGCCCGCGCTCCTCCGCAGCCTGGGGTACGCGTGAAGCCCGGGAGGCTTGGCGCCGG 
               
               
                   
                   
                 CGAAGACCCAAGGACCACTCTTCTGCGTTTGGAGTTGCTCCCCGCAACCCCGGGCTC 
               
               
                   
                   
                 GTCGCTTTCTCCATCCCGACCCACGCGGGGCGCGGGGACAACACAGGTCGCGGAGGA 
               
               
                   
                   
                 GCGTTGCCATTCAAGTGACTGCAGCAGCAGCGGCAGCGCCTCGGTTCCTGAGCCCAC 
               
               
                   
                   
                 CGCAGGCTGAAGGCATTGCGCGTAGTCCATGCCCGTAGAGGAAGTGTGCAGATGGGA 
               
               
                   
                   
                 TTAACGTCCACATGGAGATATGGAAGAGGACCGGGGATTGGTACCGTAACCATGGTC 
               
               
                   
                   
                 AGCTGGGGTCGTTTCATCTGCCTGGTCGTGGTCACCATGGCAACCTTGTCCCTGGCC 
               
               
                   
                   
                 CGGCCCTCCTTCAGTTTAGTTGAGGATACCACATTAGAGCCAGAAGATGCCATCTCA 
               
               
                   
                   
                 TCCGGAGATGATGAGGATGACACCGATGGTGCGGAAGATTTTGTCAGTGAGAACAGT 
               
               
                   
                   
                 AACAACAAGAGAGCACCATACTGGACCAACACAGAAAAGATGGAAAAGCGGCTCCAT 
               
               
                   
                   
                 GCTGTGCCTGCGGCCAACACTGTCAAGTTTCGCTGCCCAGCCGGGGGGAACCCAATG 
               
               
                   
                   
                 CCAACCATGCGGTGGCTGAAAAACGGGAAGGAGTTTAAGCAGGAGCATCGCATTGGA 
               
               
                   
                   
                 GGCTACAAGGTACGAAACCAGCACTGGAGCCTCATTATGGAAAGTGTGGTCCCATCT 
               
               
                   
                   
                 GACAAGGGAAATTATACCTGTGTAGTGGAGAATGAATACGGGTCCATCAATCACACG 
               
               
                   
                   
                 TACCACCTGGATGTTGTGGAGCGATCGCCTCACCGGCCCATCCTCCAAGCCGGACTG 
               
               
                   
                   
                 CCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGAGTTTGTCTGCAAGGTTTAC 
               
               
                   
                   
                 AGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGTGGAAAAGAACGGCAGTAAA 
               
               
                   
                   
                 TACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAAGCACTCGGGGATAAATAGT 
               
               
                   
                   
                 TCCAATGCAGAAGTGCTGGCTCTGTTCAATGTGACCGAGGCGGATGCTGGGGAATAT 
               
               
                   
                   
                 ATATGTAAGGTCTCCAATTATATAGGGCAGGCCAACCAGTCTGCCTGGCTCACTGTC 
               
               
                   
                   
                 CTGCCAAAACAGCAAGCGCCTGGAAGAGAAAAGGAGATTACAGCTTCCCCAGACTAC 
               
               
                   
                   
                 CTGGAGATAGCCATTTACTGCATAGGGGTCTTCTTAATCGCCTGTATGGTGGTAACA 
               
               
                   
                   
                 GTCATCCTGTGCCGAATGAAGAACACGACCAAGAAGCCAGACTTCAGCAGCCAGCCG 
               
               
                   
                   
                 GCTGTGCACAAGCTGACCAAACGTATCCCCCTGCGGAGACAGGTAACAGTTTCGGCT 
               
               
                   
                   
                 GAGTCCAGCTCCTCCATGAACTCCAACACCCCGCTGGTGAGGATAACAACACGCCTC 
               
               
                   
                   
                 TCTTCAACGGCAGACACCCCCATGCTGGCAGGGGTCTCCGAGTATGAACTTCCAGAG 
               
               
                   
                   
                 GACCCAAAATGGGAGTTTCCAAGAGATAAGCTGACACTGGGCAAGCCCCTGGGAGAA 
               
               
                   
                   
                 GGTTGCTTTGGGCAAGTGGTCATGGCGGAAGCAGTGGGAATTGACAAAGACAAGCCC 
               
               
                   
                   
                 AAGGAGGCGGTCACCGTGGCCGTGAAGATGTTGAAAGATGATGCCACAGAGAAAGAC 
               
               
                   
                   
                 CTTTCTGATCTGGTGTCAGAGATGGAGATGATGAAGATGATTGGGAAACACAAGAAT 
               
               
                   
                   
                 ATCATAAATCTTCTTGGAGCCTGCACACAGGATGGGCCTCTCTATGTCATAGTTGAG 
               
               
                   
                   
                 TATGCCTCTAAAGGCAACCTCCGAGAATACCTCCGAGCCCGGAGGCCACCCGGGATG 
               
               
                   
                   
                 GAGTACTCCTATGACATTAACCGTGTTCCTGAGGAGCAGATGACCTTCAAGGACTTG 
               
               
                   
                   
                 GTGTCATGCACCTACCAGCTGGCCAGAGGCATGGAGTACTTGGCTTCCCAAAAATGT 
               
               
                   
                   
                 ATTCATCGAGATTTAGCAGCCAGAAATGTTTTGGTAACAGAAAACAATGTGATGAAA 
               
               
                   
                   
                 ATAGCAGACTTTGGACTCGCCAGAGATATCAACAATATAGACTATTACAAAAAGACC 
               
               
                   
                   
                 ACCAATGGGCGGCTTCCAGTCAAGTGGATGGCTCCAGAAGCCCTGTTTGATAGAGTA 
               
               
                   
                   
                 TACACTCATCAGAGTGATGTCTGGTCCTTCGGGGTGTTAATGTGGGAGATCTTCACT 
               
               
                   
                   
                 TTAGGGGGCTCGCCCTACCCAGGGATTCCCGTGGAGGAACTTTTTAAGCTGCTGAAG 
               
               
                   
                   
                 GAAGGACACAGAATGGATAAGCCAGCCAACTGCACCAACGAACTGTACATGATGATG 
               
               
                   
                   
                 AGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAGCAGTTGGTAGAA 
               
               
                   
                   
                 GACTTGGATCGAATTCTCACTCTCACAACCAATGAGATCTGAAAGTTTATGGCTTCA 
               
               
                   
                   
                 TTGAGAAACTGGGAAAAGTTGGTCAGGCGCAGTGGCTCATGCCTGTAATCCCAGCAC 
               
               
                   
                   
                 TTTGGGAGGCCGAGGCAGGCGGATCATGAGGTCAGGAGTTCCAGACCAGCCTGGCCA 
               
               
                   
                   
                 ACATGGTGAAACCCTGTCTCTACTAAAGATACAAAAAATTAGCCGGGCGTGTTGGTG 
               
               
                   
                   
                 TGCACCTGTAATCCCAGCTACTCCGGGAGGCTGAGGCAGGAGAGTCACTTGAACCGG 
               
               
                   
                   
                 GGAGGCGGAGGTTGCAGTGAGCCGAGATCATGCCATTGCATTCCAGCCTTGGCGACA 
               
               
                   
                   
                 GAGCGAGACTCCGTCTCAAAAAAAAATAAAAA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEDAISSGDDEDDTDGAEDFVSE 
               
               
                 NO: 36 
                 isoform 9 
                 NSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHR 
               
               
                   
                 Amino acid 
                 IGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQA 
               
               
                   
                 sequence 
                 GLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKHSGI 
               
               
                   
                   
                 NSSNAEVLALFNVTEADAGEYICKVSNYIGQANQSAWLTVLPKQQAPGREKEITASP 
               
               
                   
                   
                 DYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTV 
               
               
                   
                   
                 SAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPL 
               
               
                   
                   
                 GEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKH 
               
               
                   
                   
                 KNIINLLGACTQDGPLYV IVEYASKGNLR EYLRARRPPGMEYSYDINRVPEEQMTFK 
               
               
                   
                   
                 DLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYK 
               
               
                   
                   
                 KTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKL 
               
               
                   
                   
                 LKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEI 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 GGACCGGGGATTGGTACCGTAACCATGGTCAGCTGGGGTCGTTTCATCTGCCTGGTC 
               
               
                 NO: 37 
                 isoform 10 
                 GTGGTCACCATGGCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTTAGTTGAGGAT 
               
               
                   
                 Nucleic acid 
                 ACCACATTAGAGCCAGAAGAGCCACCAACCAAATACCAAATCTCTCAACCAGAAGTG 
               
               
                   
                 sequence 
                 TACGTGGCTGCGCCAGGGGAGTCGCTAGAGGTGCGCTGCCTGTTGAAAGATGCCGCC 
               
               
                   
                   
                 GTGATCAGTTGGACTAAGGATGGGGTGCACTTGGGGCCCAACAATAGGACAGTGCTT 
               
               
                   
                   
                 ATTGGGGAGTACTTGCAGATAAAGGGCGCCACGCCTAGAGACTCCGGCCTCTATGCT 
               
               
                   
                   
                 TGTACTGCCAGTAGGACTGTAGACAGTGAAACTTGGTACTTCATGGTGAATGTCACA 
               
               
                   
                   
                 GATGCCATCTCATCCGGAGATGATGAGGATGACACCGATGGTGCGGAAGATTTTGTC 
               
               
                   
                   
                 AGTGAGAACAGTAACAACAAGAGAGCACCATACTGGACCAACACAGAAAAGATGGAA 
               
               
                   
                   
                 AAGCGGCTCCATGCTGTGCCTGCGGCCAACACTGTCAAGTTTCGCTGCCCAGCCGGG 
               
               
                   
                   
                 GGGAACCCAATGCCAACCATGCGGTGGCTGAAAAACGGGAAGGAGTTTAAGCAGGAG 
               
               
                   
                   
                 CATCGCATTGGAGGCTACAAGGTACGAAACCAGCACTGGAGCCTCATTATGGAAAGT 
               
               
                   
                   
                 GTGGTCCCATCTGACAAGGGAAATTATACCTGTGTAGTGGAGAATGAATACGGGTCC 
               
               
                   
                   
                 ATCAATCACACGTACCACCTGGATGTTGTGGAGCGATCGCCTCACCGGCCCATCCTC 
               
               
                   
                   
                 CAAGCCGGACTGCCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGAGTTTGTC 
               
               
                   
                   
                 TGCAAGGTTTACAGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGTGGAAAAG 
               
               
                   
                   
                 AACGGCAGTAAATACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAAGCACTCG 
               
               
                   
                   
                 GGGATAAATAGTTCCAATGCAGAAGTGCTGGCTCTGTTCAATGTGACCGAGGCGGAT 
               
               
                   
                   
                 GCTGGGGAATATATATGTAAGGTCTCCAATTATATAGGGCAGGCCAACCAGTCTGCC 
               
               
                   
                   
                 TGGCTCACTGTCCTGCCAAAACAGCAAGCGCCTGGAAGAGAAAAGGAGATTACAGCT 
               
               
                   
                   
                 TCCCCAGACTACCTGGAGATAGCCATTTACTGCATAGGGGTCTTCTTAATCGCCTGT 
               
               
                   
                   
                 ATGGTGGTAACAGTCATCCTGTGCCGAATGAAGAACACGACCAAGAAGCCAGACTTC 
               
               
                   
                   
                 AGCAGCCAGCCGGCTGTGCACAAGCTGACCAAACGTATCCCCCTGCGGAGACAGGTA 
               
               
                   
                   
                 ACAGTTTCGGCTGAGTCCAGCTCCTCCATGAACTCCAACACCCCGCTGGTGAGGATA 
               
               
                   
                   
                 ACAACACGCCTCTCTTCAACGGCAGACACCCCCATGCTGGCAGGGGTCTCCGAGTAT 
               
               
                   
                   
                 GAACTTCCAGAGGACCCAAAATGGGAGTTTCCAAGAGATAAGCTGACACTGGGCAAG 
               
               
                   
                   
                 CCCCTGGGAGAAGGTTGCTTTGGGCAAGTGGTCATGGCGGAAGCAGTGGGAATTGAC 
               
               
                   
                   
                 AAAGACAAGCCCAAGGAGGCGGTCACCGTGGCCGTGAAGATGTTGAAAGATGATGCC 
               
               
                   
                   
                 ACAGAGAAAGACCTTTCTGATCTGGTGTCAGAGATGGAGATGATGAAGATGATTGGG 
               
               
                   
                   
                 AAACACAAGAATATCATAAATCTTCTTGGAGCCTGCACACAGGATGGGCCTCTCTAT 
               
               
                   
                   
                 GTCATAGTTGAGTATGCCTCTAAAGGCAACCTCCGAGAATACCTCCGAGCCCGGAGG 
               
               
                   
                   
                 CCACCCGGGATGGAGTACTCCTATGACATTAACCGTGTTCCTGAGGAGCAGATGACC 
               
               
                   
                   
                 TTCAAGGACTTGGTGTCATGCACCTACCAGCTGGCCAGAGGCATGGAGTACTTGGCT 
               
               
                   
                   
                 TCCCAAAAATGTATTCATCGAGATTTAGCAGCCAGAAATGTTTTGGTAACAGAAAAC 
               
               
                   
                   
                 AATGTGATGAAAATAGCAGACTTTGGACTCGCCAGAGATATCAACAATATAGACTAT 
               
               
                   
                   
                 TACAAAAAGACCACCAATGGGCGGCTTCCAGTCAAGTGGATGGCTCCAGAAGCCCTG 
               
               
                   
                   
                 TTTGATAGAGTATACACTCATCAGAGTGATGTCTGGTCCTTCGGGGTGTTAATGTGG 
               
               
                   
                   
                 GAGATCTTCACTTTAGGGGGCTCGCCCTACCCAGGGATTCCCGTGGAGGAACTTTTT 
               
               
                   
                   
                 AAGCTGCTGAAGGAAGGACACAGAATGGATAAGCCAGCCAACTGCACCAACGAACTG 
               
               
                   
                   
                 TACATGATGATGAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAG 
               
               
                   
                   
                 CAGTTGGTAGAAGACTTGGATCGAATTCTCACTCTCACAACCAATGAGATCTGAAAG 
               
               
                   
                   
                 TTTATGGCTTCATTGAGAAACTGGGAAAAGTTGGTCAGGCGCAGTGGCTCATGCCTG 
               
               
                   
                   
                 TAATCCCAGCACTTTGGGAGGCCGAGGCAGGCGGATCATGAGGTCAGGAGTTCCAGA 
               
               
                   
                   
                 CCAGCCTGGCCAACATGGTGAAACCCTGTCTCTACTAAAGATACAAAAAATTAGCCG 
               
               
                   
                   
                 GGCGTGTTGGTGTGCACCTGTAATCCCAGCTACTCCGGGAGGCTGAGGCAGGAGAGT 
               
               
                   
                   
                 CACTTGAACCGGGGAGGCGGAGGTTGCAGTGAGCCGAGATCATGCCATTGCATTCCA 
               
               
                   
                   
                 GCCTTGGCGACAGAGCGAGACTCCGTCT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGES 
               
               
                 NO: 38 
                 isoform 10 
                 LEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVD 
               
               
                   
                 Amino acid 
                 SETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPA 
               
               
                   
                 sequence 
                 ANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGN 
               
               
                   
                   
                 YTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQ 
               
               
                   
                   
                 PHIQWIKHVEKNGSKYGPDGLPYLKVLKHSGINSSNAEVLALFNVTEADAGEYICKV 
               
               
                   
                   
                 SNYIGQANQSAWLTVLPKQQAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILC 
               
               
                   
                   
                 RMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTA 
               
               
                   
                   
                 DTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAV 
               
               
                   
                   
                 TVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASK   
               
               
                   
                   
                   GNLR EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRD 
               
               
                   
                   
                 LAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQ 
               
               
                   
                   
                 SDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCW 
               
               
                   
                   
                 HAVPSQRPTFKQLVEDLDRILTLTTNEI 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 GGTACCGTAACCATGGTCAGCTGGGGTCGTTTCATCTGCCTGGTCGTGGTCACCATG 
               
               
                 NO: 39 
                 isoform 11 
                 GCAACCTTGTCCCTGGCCCGGCCCTCCTTCAGTTTAGTTGAGGATACCACATTAGAG 
               
               
                   
                 Nucleic acid 
                 CCAGAAGAGCCACCAACCAAATACCAAATCTCTCAACCAGAAGTGTACGTGGCTGCG 
               
               
                   
                 sequence 
                 CCAGGGGAGTCGCTAGAGGTGCGCTGCCTGTTGAAAGATGCCGCCGTGATCAGTTGG 
               
               
                   
                   
                 ACTAAGGATGGGGTGCACTTGGGGCCCAACAATAGGACAGTGCTTATTGGGGAGTAC 
               
               
                   
                   
                 TTGCAGATAAAGGGCGCCACGCCTAGAGACTCCGGCCTCTATGCTTGTACTGCCAGT 
               
               
                   
                   
                 AGGACTGTAGACAGTGAAACTTGGTACTTCATGGTGAATGTCACAGATGCCATCTCA 
               
               
                   
                   
                 TCCGGAGATGATGAGGATGACACCGATGGTGCGGAAGATTTTGTCAGTGAGAACAGT 
               
               
                   
                   
                 AACAACAAGAGAGCACCATACTGGACCAACACAGAAAAGATGGAAAAGCGGCTCCAT 
               
               
                   
                   
                 GCTGTGCCTGCGGCCAACACTGTCAAGTTTCGCTGCCCAGCCGGGGGGAACCCAATG 
               
               
                   
                   
                 CCAACCATGCGGTGGCTGAAAAACGGGAAGGAGTTTAAGCAGGAGCATCGCATTGGA 
               
               
                   
                   
                 GGCTACAAGGTACGAAACCAGCACTGGAGCCTCATTATGGAAAGTGTGGTCCCATCT 
               
               
                   
                   
                 GACAAGGGAAATTATACCTGTGTAGTGGAGAATGAATACGGGTCCATCAATCACACG 
               
               
                   
                   
                 TACCACCTGGATGTTGTGGAGCGATCGCCTCACCGGCCCATCCTCCAAGCCGGACTG 
               
               
                   
                   
                 CCGGCAAATGCCTCCACAGTGGTCGGAGGAGACGTAGAGTTTGTCTGCAAGGTTTAC 
               
               
                   
                   
                 AGTGATGCCCAGCCCCACATCCAGTGGATCAAGCACGTGGAAAAGAACGGCAGTAAA 
               
               
                   
                   
                 TACGGGCCCGACGGGCTGCCCTACCTCAAGGTTCTCAAGGCCGCCGGTGTTAACACC 
               
               
                   
                   
                 ACGGACAAAGAGATTGAGGTTCTCTATATTCGGAATGTAACTTTTGAGGACGCTGGG 
               
               
                   
                   
                 GAATATACGTGCTTGGCGGGTAATTCTATTGGGATATCCTTTCACTCTGCATGGTTG 
               
               
                   
                   
                 ACAGTTCTGCCAGCGCCTGGAAGAGAAAAGGAGATTACAGCTTCCCCAGACTACCTG 
               
               
                   
                   
                 GAGATAGCCATTTACTGCATAGGGGTCTTCTTAATCGCCTGTATGGTGGTAACAGTC 
               
               
                   
                   
                 ATCCTGTGCCGAATGAAGAACACGACCAAGAAGCCAGACTTCAGCAGCCAGCCGGCT 
               
               
                   
                   
                 GTGCACAAGCTGACCAAACGTATCCCCCTGCGGAGACAGGTTTCGGCTGAGTCCAGC 
               
               
                   
                   
                 TCCTCCATGAACTCCAACACCCCGCTGGTGAGGATAACAACACGCCTCTCTTCAACG 
               
               
                   
                   
                 GCAGACACCCCCATGCTGGCAGGGGTCTCCGAGTATGAACTTCCAGAGGACCCAAAA 
               
               
                   
                   
                 TGGGAGTTTCCAAGAGATAAGCTGACACTGGGCAAGCCCCTGGGAGAAGGTTGCTTT 
               
               
                   
                   
                 GGGCAAGTGGTCATGGCGGAAGCAGTGGGAATTGACAAAGACAAGCCCAAGGAGGCG 
               
               
                   
                   
                 GTCACCGTGGCCGTGAAGATGTTGAAAGATGATGCCACAGAGAAAGACCTTTCTGAT 
               
               
                   
                   
                 CTGGTGTCAGAGATGGAGATGATGAAGATGATTGGGAAACACAAGAATATCATAAAT 
               
               
                   
                   
                 CTTCTTGGAGCCTGCACACAGGATGGGCCTCTCTATGTCATAGTTGAGTATGCCTCT 
               
               
                   
                   
                 AAAGGCAACCTCCGAGAATACCTCCGAGCCCGGAGGCCACCCGGGATGGAGTACTCC 
               
               
                   
                   
                 TATGACATTAACCGTGTTCCTGAGGAGCAGATGACCTTCAAGGACTTGGTGTCATGC 
               
               
                   
                   
                 ACCTACCAGCTGGCCAGAGGCATGGAGTACTTGGCTTCCCAAAAATGTATTCATCGA 
               
               
                   
                   
                 GATTTAGCAGCCAGAAATGTTTTGGTAACAGAAAACAATGTGATGAAAATAGCAGAC 
               
               
                   
                   
                 TTTGGACTCGCCAGAGATATCAACAATATAGACTATTACAAAAAGACCACCAATGGG 
               
               
                   
                   
                 CGGCTTCCAGTCAAGTGGATGGCTCCAGAAGCCCTGTTTGATAGAGTATACACTCAT 
               
               
                   
                   
                 CAGAGTGATGTCTGGTCCTTCGGGGTGTTAATGTGGGAGATCTTCACTTTAGGGGGC 
               
               
                   
                   
                 TCGCCCTACCCAGGGATTCCCGTGGAGGAACTTTTTAAGCTGCTGAAGGAAGGACAC 
               
               
                   
                   
                 AGAATGGATAAGCCAGCCAACTGCACCAACGAACTGTACATGATGATGAGGGACTGT 
               
               
                   
                   
                 TGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAGCAGTTGGTAGAAGACTTGGAT 
               
               
                   
                   
                 CGAATTCTCACTCTCACAACCAATGAGGAATACTTGGACCTCAGCCAACCTCTCGAA 
               
               
                   
                   
                 CAGTATTCACCTAGTTACCCTGACACAAGAAGTTCTTGTTCTTCAGGAGATGATTCT 
               
               
                   
                   
                 GTTTTTTCTCCAGACCCCATGCCTTACGAACCATGCCTTCCTCAGTATCCACACATA 
               
               
                   
                   
                 AACGGCAGTGTTAAAACATGA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGES 
               
               
                 NO: 40 
                 isoform 11 
                 LEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVD 
               
               
                   
                 Amino acid 
                 SETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPA 
               
               
                   
                 sequence 
                 ANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGN 
               
               
                   
                   
                 YTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQ 
               
               
                   
                   
                 PHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTC 
               
               
                   
                   
                 LAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCR 
               
               
                   
                   
                 MKNTTKKPDFSSQPAVHKLTKRIPLRRQVSAESSSSMNSNTPLVRITTRLSSTADTP 
               
               
                   
                   
                 MLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVA 
               
               
                   
                   
                 VKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYV IVEYASKGNL   
               
               
                   
                   
                   R EYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAA 
               
               
                   
                   
                 RNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDV 
               
               
                   
                   
                 WSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAV 
               
               
                   
                   
                 PSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSP 
               
               
                   
                   
                 DPMPYEPCLPQYPHINGSVKT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 AGTGCGCGGTGGCGGCGGCGTCGCGGGCAGCTGGCGCCGCGCGGTCCTGCTCTGCCG 
               
               
                 NO: 41 
                 isoform 1 
                 GTCGCACGGACGCACCGGCGGGCCGCCGGCCGGAGGGACGGGGCGGGAGCTGGGCCC 
               
               
                   
                 Nucleic acid 
                 GCGGACAGCGAGCCGGAGCGGGAGCCGCGCGTAGCGAGCCGGGCTCCGGCGCTCGCC 
               
               
                   
                 sequence 
                 AGTCTCCCGAGCGGCGCCCGCCTCCCGCCGGTGCCCGCGCCGGGCCGTGGGGGGCAG 
               
               
                   
                   
                 CATGCCCGCGCGCGCTGCCTGAGGACGCCGCGGCCCCCGCCCCCGCCATGGGCGCCC 
               
               
                   
                   
                 CTGCCTGCGCCCTCGCGCTCTGCGTGGCCGTGGCCATCGTGGCCGGCGCCTCCTCGG 
               
               
                   
                   
                 AGTCCTTGGGGACGGAGCAGCGCGTCGTGGGGCGAGCGGCAGAAGTCCCGGGCCCAG 
               
               
                   
                   
                 AGCCCGGCCAGCAGGAGCAGTTGGTCTTCGGCAGCGGGGATGCTGTGGAGCTGAGCT 
               
               
                   
                   
                 GTCCCCCGCCCGGGGGTGGTCCCATGGGGCCCACTGTCTGGGTCAAGGATGGCACAG 
               
               
                   
                   
                 GGCTGGTGCCCTCGGAGCGTGTCCTGGTGGGGCCCCAGCGGCTGCAGGTGCTGAATG 
               
               
                   
                   
                 CCTCCCACGAGGACTCCGGGGCCTACAGCTGCCGGCAGCGGCTCACGCAGCGCGTAC 
               
               
                   
                   
                 TGTGCCACTTCAGTGTGCGGGTGACAGACGCTCCATCCTCGGGAGATGACGAAGACG 
               
               
                   
                   
                 GGGAGGACGAGGCTGAGGACACAGGTGTGGACACAGGGGCCCCTTACTGGACACGGC 
               
               
                   
                   
                 CCGAGCGGATGGACAAGAAGCTGCTGGCCGTGCCGGCCGCCAACACCGTCCGCTTCC 
               
               
                   
                   
                 GCTGCCCAGCCGCTGGCAACCCCACTCCCTCCATCTCCTGGCTGAAGAACGGCAGGG 
               
               
                   
                   
                 AGTTCCGCGGCGAGCACCGCATTGGAGGCATCAAGCTGCGGCATCAGCAGTGGAGCC 
               
               
                   
                   
                 TGGTCATGGAAAGCGTGGTGCCCTCGGACCGCGGCAACTACACCTGCGTCGTGGAGA 
               
               
                   
                   
                 ACAAGTTTGGCAGCATCCGGCAGACGTACACGCTGGACGTGCTGGAGCGCTCCCCGC 
               
               
                   
                   
                 ACCGGCCCATCCTGCAGGCGGGGCTGCCGGCCAACCAGACGGCGGTGCTGGGCAGCG 
               
               
                   
                   
                 ACGTGGAGTTCCACTGCAAGGTGTACAGTGACGCACAGCCCCACATCCAGTGGCTCA 
               
               
                   
                   
                 AGCACGTGGAGGTGAATGGCAGCAAGGTGGGCCCGGACGGCACACCCTACGTTACCG 
               
               
                   
                   
                 TGCTCAAGACGGCGGGCGCTAACACCACCGACAAGGAGCTAGAGGTTCTCTCCTTGC 
               
               
                   
                   
                 ACAACGTCACCTTTGAGGACGCCGGGGAGTACACCTGCCTGGCGGGCAATTCTATTG 
               
               
                   
                   
                 GGTTTTCTCATCACTCTGCGTGGCTGGTGGTGCTGCCAGCCGAGGAGGAGCTGGTGG 
               
               
                   
                   
                 AGGCTGACGAGGCGGGCAGTGTGTATGCAGGCATCCTCAGCTACGGGGTGGGCTTCT 
               
               
                   
                   
                 TCCTGTTCATCCTGGTGGTGGCGGCTGTGACGCTCTGCCGCCTGCGCAGCCCCCCCA 
               
               
                   
                   
                 AGAAAGGCCTGGGCTCCCCCACCGTGCACAAGATCTCCCGCTTCCCGCTCAAGCGAC 
               
               
                   
                   
                 AGGTGTCCCTGGAGTCCAACGCGTCCATGAGCTCCAACACACCACTGGTGCGCATCG 
               
               
                   
                   
                 CAAGGCTGTCCTCAGGGGAGGGCCCCACGCTGGCCAATGTCTCCGAGCTCGAGCTGC 
               
               
                   
                   
                 CTGCCGACCCCAAATGGGAGCTGTCTCGGGCCCGGCTGACCCTGGGCAAGCCCCTTG 
               
               
                   
                   
                 GGGAGGGCTGCTTCGGCCAGGTGGTCATGGCGGAGGCCATCGGCATTGACAAGGACC 
               
               
                   
                   
                 GGGCCGCCAAGCCTGTCACCGTAGCCGTGAAGATGCTGAAAGACGATGCCACTGACA 
               
               
                   
                   
                 AGGACCTGTCGGACCTGGTGTCTGAGATGGAGATGATGAAGATGATCGGGAAACACA 
               
               
                   
                   
                 AAAACATCATCAACCTGCTGGGCGCCTGCACGCAGGGCGGGCCCCTGTACGTGCTGG 
               
               
                   
                   
                 TGGAGTACGCGGCCAAGGGTAACCTGCGGGAGTTTCTGCGGGCGCGGCGGCCCCCGG 
               
               
                   
                   
                 GCCTGGACTACTCCTTCGACACCTGCAAGCCGCCCGAGGAGCAGCTCACCTTCAAGG 
               
               
                   
                   
                 ACCTGGTGTCCTGTGCCTACCAGGTGGCCCGGGGCATGGAGTACTTGGCCTCCCAGA 
               
               
                   
                   
                 AGTGCATCCACAGGGACCTGGCTGCCCGCAATGTGCTGGTGACCGAGGACAACGTGA 
               
               
                   
                   
                 TGAAGATCGCAGACTTCGGGCTGGCCCGGGACGTGCACAACCTCGACTACTACAAGA 
               
               
                   
                   
                 AGACGACCAACGGCCGGCTGCCCGTGAAGTGGATGGCGCCTGAGGCCTTGTTTGACC 
               
               
                   
                   
                 GAGTCTACACTCACCAGAGTGACGTCTGGTCCTTTGGGGTCCTGCTCTGGGAGATCT 
               
               
                   
                   
                 TCACGCTGGGGGGCTCCCCGTACCCCGGCATCCCTGTGGAGGAGCTCTTCAAGCTGC 
               
               
                   
                   
                 TGAAGGAGGGCCACCGCATGGACAAGCCCGCCAACTGCACACACGACCTGTACATGA 
               
               
                   
                   
                 TCATGCGGGAGTGCTGGCATGCCGCGCCCTCCCAGAGGCCCACCTTCAAGCAGCTGG 
               
               
                   
                   
                 TGGAGGACCTGGACCGTGTCCTTACCGTGACGTCCACCGACGAGTACCTGGACCTGT 
               
               
                   
                   
                 CGGCGCCTTTCGAGCAGTACTCCCCGGGTGGCCAGGACACCCCCAGCTCCAGCTCCT 
               
               
                   
                   
                 CAGGGGACGACTCCGTGTTTGCCCACGACCTGCTGCCCCCGGCCCCACCCAGCAGTG 
               
               
                   
                   
                 GGGGCTCGCGGACGTGAAGGGCCACTGGTCCCCAACAATGTGAGGGGTCCCTAGCAG 
               
               
                   
                   
                 CCCACCCTGCTGCTGGTGCACAGCCACTCCCCGGCATGAGACTCAGTGCAGATGGAG 
               
               
                   
                   
                 AGACAGCTACACAGAGCTTTGGTCTGTGTGTGTGTGTGTGCGTGTGTGTGTGTGTGT 
               
               
                   
                   
                 GTGCACATCCGCGTGTGCCTGTGTGCGTGCGCATCTTGCCTCCAGGTGCAGAGGTAC 
               
               
                   
                   
                 CCTGGGTGTCCCCGCTGCTGTGCAACGGTCTCCTGACTGGTGCTGCAGCACCGAGGG 
               
               
                   
                   
                 GCCTTTGTTCTGGGGGGACCCAGTGCAGAATGTAAGTGGGCCCACCCGGTGGGACCC 
               
               
                   
                   
                 CCGTGGGGCAGGGAGCTGGGCCCGACATGGCTCCGGCCTCTGCCTTTGCACCACGGG 
               
               
                   
                   
                 ACATCACAGGGTGGGCCTCGGCCCCTCCCACACCCAAAGCTGAGCCTGCAGGGAAGC 
               
               
                   
                   
                 CCCACATGTCCAGCACCTTGTGCCTGGGGTGTTAGTGGCACCGCCTCCCCACCTCCA 
               
               
                   
                   
                 GGCTTTCCCACTTCCCACCCTGCCCCTCAGAGACTGAAATTACGGGTACCTGAAGAT 
               
               
                   
                   
                 GGGAGCCTTTACCTTTTATGCAAAAGGTTTATTCCGGAAACTAGTGTACATTTCTAT 
               
               
                   
                   
                 AAATAGATGCTGTGTATATGGTATATATACATATATATATATAACATATATGGAAGA 
               
               
                   
                   
                 GGAAAAGGCTGGTACAACGGAGGCCTGCGACCCTGGGGGCACAGGAGGCAGGCATGG 
               
               
                   
                   
                 CCCTGGGCGGGGCGTGGGGGGGCGTGGAGGGAGGCCCCAGGGGGTCTCACCCATGCA 
               
               
                   
                   
                 AGCAGAGGACCAGGGCCTTTTCTGGCACCGCAGTTTTGTTTTAAAACTGGACCTGTA 
               
               
                   
                   
                 TATTTGTAAAGCTATTTATGGGCCCCTGGCACTCTTGTTCCCACACCCCAACACTTC 
               
               
                   
                   
                 CAGCATTTAGCTGGCCACATGGCGGAGAGTTTTAATTTTTAACTTATTGACAACCGA 
               
               
                   
                   
                 GAAGGTTTATCCCGCCGATAGAGGGACGGCCAAGAATGTACGTCCAGCCTGCCCCGG 
               
               
                   
                   
                 AGCTGGAGGATCCCCTCCAAGCCTAAAAGGTTGTTAATAGTTGGAGGTGATTCCAGT 
               
               
                   
                   
                 GAAGATATTTTATTTCCTTTGTCCTTTTTCAGGAGAATTAGATTTCTATAGGATTTT 
               
               
                   
                   
                 TCTTTAGGAGATTTATTTTTTGGACTTCAAAGCAAGCTGGTATTTTCATACAAATTC 
               
               
                   
                   
                 TTCTAATTGCTGTGTGTCCCAGGCAGGGAGACGGTTTCCAGGGAGGGGCCGGCCCTG 
               
               
                   
                   
                 TGTGCAGGTTCCGATGTTATTAGATGTTACAAGTTTATATATATCTATATATATAAT 
               
               
                   
                   
                 TTATTGAGTTTTTACAAGATGTATTTGTTGTAGACTTAACACTTCTTACGCAATGCT 
               
               
                   
                   
                 TCTAGAGTTTTATAGCCTGGACTGCTACCTTTCAAAGCTTGGAGGGAAGCCGTGAAT 
               
               
                   
                   
                 TCAGTTGGTTCGTTCTGTACTGTTACTGGGCCCTGAGTCTGGGCAGCTGTCCCTTGC 
               
               
                   
                   
                 TTGCCTGCAGGGCCATGGCTCAGGGTGGTCTCTTCTTGGGGCCCAGTGCATGGTGGC 
               
               
                   
                   
                 CAGAGGTGTCACCCAAACCGGCAGGTGCGATTTTGTTAACCCAGCGACGAACTTTCC 
               
               
                   
                   
                 GAAAAATAAAGACACCTGGTTGCTAACCTGG 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAV 
               
               
                 NO: 42 
                 isoform 1 
                 ELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLT 
               
               
                   
                 Amino acid 
                 QRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANT 
               
               
                   
                 sequence 
                 VRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTC 
               
               
                   
                   
                 VVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHI 
               
               
                   
                   
                 QWLKHVEVNGSKVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAG 
               
               
                   
                   
                 NSIGFSHHSAWLVVLPAEEELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLR 
               
               
                   
                   
                 SPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGPTLANVSE 
               
               
                   
                   
                 LELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDD 
               
               
                   
                   
                 ATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYV LVEYAAKGNLR EFLRAR 
               
               
                   
                   
                 RPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTE 
               
               
                   
                   
                 DNVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLL 
               
               
                   
                   
                 WEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTF 
               
               
                   
                   
                 KQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAP 
               
               
                   
                   
                 PSSGGSRT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 GTCGCGGGCAGCTGGCGCCGCGCGGTCCTGCTCTGCCGGTCGCACGGACGCACCGGC 
               
               
                 NO: 43 
                 isoform 2 
                 GGGCCGCCGGCCGGAGGGACGGGGCGGGAGCTGGGCCCGCGGACAGCGAGCCGGAGC 
               
               
                   
                 Nucleic acid 
                 GGGAGCCGCGCGTAGCGAGCCGGGCTCCGGCGCTCGCCAGTCTCCCGAGCGGCGCCC 
               
               
                   
                 sequence 
                 GCCTCCCGCCGGTGCCCGCGCCGGGCCGTGGGGGGCAGCATGCCCGCGCGCGCTGCC 
               
               
                   
                   
                 TGAGGACGCCGCGGCCCCCGCCCCCGCCATGGGCGCCCCTGCCTGCGCCCTCGCGCT 
               
               
                   
                   
                 CTGCGTGGCCGTGGCCATCGTGGCCGGCGCCTCCTCGGAGTCCTTGGGGACGGAGCA 
               
               
                   
                   
                 GCGCGTCGTGGGGCGAGCGGCAGAAGTCCCGGGCCCAGAGCCCGGCCAGCAGGAGCA 
               
               
                   
                   
                 GTTGGTCTTCGGCAGCGGGGATGCTGTGGAGCTGAGCTGTCCCCCGCCCGGGGGTGG 
               
               
                   
                   
                 TCCCATGGGGCCCACTGTCTGGGTCAAGGATGGCACAGGGCTGGTGCCCTCGGAGCG 
               
               
                   
                   
                 TGTCCTGGTGGGGCCCCAGCGGCTGCAGGTGCTGAATGCCTCCCACGAGGACTCCGG 
               
               
                   
                   
                 GGCCTACAGCTGCCGGCAGCGGCTCACGCAGCGCGTACTGTGCCACTTCAGTGTGCG 
               
               
                   
                   
                 GGTGACAGACGCTCCATCCTCGGGAGATGACGAAGACGGGGAGGACGAGGCTGAGGA 
               
               
                   
                   
                 CACAGGTGTGGACACAGGGGCCCCTTACTGGACACGGCCCGAGCGGATGGACAAGAA 
               
               
                   
                   
                 GCTGCTGGCCGTGCCGGCCGCCAACACCGTCCGCTTCCGCTGCCCAGCCGCTGGCAA 
               
               
                   
                   
                 CCCCACTCCCTCCATCTCCTGGCTGAAGAACGGCAGGGAGTTCCGCGGCGAGCACCG 
               
               
                   
                   
                 CATTGGAGGCATCAAGCTGCGGCATCAGCAGTGGAGCCTGGTCATGGAAAGCGTGGT 
               
               
                   
                   
                 GCCCTCGGACCGCGGCAACTACACCTGCGTCGTGGAGAACAAGTTTGGCAGCATCCG 
               
               
                   
                   
                 GCAGACGTACACGCTGGACGTGCTGGAGCGCTCCCCGCACCGGCCCATCCTGCAGGC 
               
               
                   
                   
                 GGGGCTGCCGGCCAACCAGACGGCGGTGCTGGGCAGCGACGTGGAGTTCCACTGCAA 
               
               
                   
                   
                 GGTGTACAGTGACGCACAGCCCCACATCCAGTGGCTCAAGCACGTGGAGGTGAATGG 
               
               
                   
                   
                 CAGCAAGGTGGGCCCGGACGGCACACCCTACGTTACCGTGCTCAAGTCCTGGATCAG 
               
               
                   
                   
                 TGAGAGTGTGGAGGCCGACGTGCGCCTCCGCCTGGCCAATGTGTCGGAGCGGGACGG 
               
               
                   
                   
                 GGGCGAGTACCTCTGTCGAGCCACCAATTTCATAGGCGTGGCCGAGAAGGCCTTTTG 
               
               
                   
                   
                 GCTGAGCGTTCACGGGCCCCGAGCAGCCGAGGAGGAGCTGGTGGAGGCTGACGAGGC 
               
               
                   
                   
                 GGGCAGTGTGTATGCAGGCATCCTCAGCTACGGGGTGGGCTTCTTCCTGTTCATCCT 
               
               
                   
                   
                 GGTGGTGGCGGCTGTGACGCTCTGCCGCCTGCGCAGCCCCCCCAAGAAAGGCCTGGG 
               
               
                   
                   
                 CTCCCCCACCGTGCACAAGATCTCCCGCTTCCCGCTCAAGCGACAGGTGTCCCTGGA 
               
               
                   
                   
                 GTCCAACGCGTCCATGAGCTCCAACACACCACTGGTGCGCATCGCAAGGCTGTCCTC 
               
               
                   
                   
                 AGGGGAGGGCCCCACGCTGGCCAATGTCTCCGAGCTCGAGCTGCCTGCCGACCCCAA 
               
               
                   
                   
                 ATGGGAGCTGTCTCGGGCCCGGCTGACCCTGGGCAAGCCCCTTGGGGAGGGCTGCTT 
               
               
                   
                   
                 CGGCCAGGTGGTCATGGCGGAGGCCATCGGCATTGACAAGGACCGGGCCGCCAAGCC 
               
               
                   
                   
                 TGTCACCGTAGCCGTGAAGATGCTGAAAGACGATGCCACTGACAAGGACCTGTCGGA 
               
               
                   
                   
                 CCTGGTGTCTGAGATGGAGATGATGAAGATGATCGGGAAACACAAAAACATCATCAA 
               
               
                   
                   
                 CCTGCTGGGCGCCTGCACGCAGGGCGGGCCCCTGTACGTGCTGGTGGAGTACGCGGC 
               
               
                   
                   
                 CAAGGGTAACCTGCGGGAGTTTCTGCGGGCGCGGCGGCCCCCGGGCCTGGACTACTC 
               
               
                   
                   
                 CTTCGACACCTGCAAGCCGCCCGAGGAGCAGCTCACCTTCAAGGACCTGGTGTCCTG 
               
               
                   
                   
                 TGCCTACCAGGTGGCCCGGGGCATGGAGTACTTGGCCTCCCAGAAGTGCATCCACAG 
               
               
                   
                   
                 GGACCTGGCTGCCCGCAATGTGCTGGTGACCGAGGACAACGTGATGAAGATCGCAGA 
               
               
                   
                   
                 CTTCGGGCTGGCCCGGGACGTGCACAACCTCGACTACTACAAGAAGACGACCAACGG 
               
               
                   
                   
                 CCGGCTGCCCGTGAAGTGGATGGCGCCTGAGGCCTTGTTTGACCGAGTCTACACTCA 
               
               
                   
                   
                 CCAGAGTGACGTCTGGTCCTTTGGGGTCCTGCTCTGGGAGATCTTCACGCTGGGGGG 
               
               
                   
                   
                 CTCCCCGTACCCCGGCATCCCTGTGGAGGAGCTCTTCAAGCTGCTGAAGGAGGGCCA 
               
               
                   
                   
                 CCGCATGGACAAGCCCGCCAACTGCACACACGACCTGTACATGATCATGCGGGAGTG 
               
               
                   
                   
                 CTGGCATGCCGCGCCCTCCCAGAGGCCCACCTTCAAGCAGCTGGTGGAGGACCTGGA 
               
               
                   
                   
                 CCGTGTCCTTACCGTGACGTCCACCGACGAGTACCTGGACCTGTCGGCGCCTTTCGA 
               
               
                   
                   
                 GCAGTACTCCCCGGGTGGCCAGGACACCCCCAGCTCCAGCTCCTCAGGGGACGACTC 
               
               
                   
                   
                 CGTGTTTGCCCACGACCTGCTGCCCCCGGCCCCACCCAGCAGTGGGGGCTCGCGGAC 
               
               
                   
                   
                 GTGAAGGGCCACTGGTCCCCAACAATGTGAGGGGTCCCTAGCAGCCCACCCTGCTGC 
               
               
                   
                   
                 TGGTGCACAGCCACTCCCCGGCATGAGACTCAGTGCAGATGGAGAGACAGCTACACA 
               
               
                   
                   
                 GAGCTTTGGTCTGTGTGTGTGTGTGTGCGTGTGTGTGTGTGTGTGTGCACATCCGCG 
               
               
                   
                   
                 TGTGCCTGTGTGCGTGCGCATCTTGCCTCCAGGTGCAGAGGTACCCTGGGTGTCCCC 
               
               
                   
                   
                 GCTGCTGTGCAACGGTCTCCTGACTGGTGCTGCAGCACCGAGGGGCCTTTGTTCTGG 
               
               
                   
                   
                 GGGGACCCAGTGCAGAATGTAAGTGGGCCCACCCGGTGGGACCCCCGTGGGGCAGGG 
               
               
                   
                   
                 AGCTGGGCCCGACATGGCTCCGGCCTCTGCCTTTGCACCACGGGACATCACAGGGTG 
               
               
                   
                   
                 GGCCTCGGCCCCTCCCACACCCAAAGCTGAGCCTGCAGGGAAGCCCCACATGTCCAG 
               
               
                   
                   
                 CACCTTGTGCCTGGGGTGTTAGTGGCACCGCCTCCCCACCTCCAGGCTTTCCCACTT 
               
               
                   
                   
                 CCCACCCTGCCCCTCAGAGACTGAAATTACGGGTACCTGAAGATGGGAGCCTTTACC 
               
               
                   
                   
                 TTTTATGCAAAAGGTTTATTCCGGAAACTAGTGTACATTTCTATAAATAGATGCTGT 
               
               
                   
                   
                 GTATATGGTATATATACATATATATATATAACATATATGGAAGAGGAAAAGGCTGGT 
               
               
                   
                   
                 ACAACGGAGGCCTGCGACCCTGGGGGCACAGGAGGCAGGCATGGCCCTGGGCGGGGC 
               
               
                   
                   
                 GTGGGGGGGCGTGGAGGGAGGCCCCAGGGGGTCTCACCCATGCAAGCAGAGGACCAG 
               
               
                   
                   
                 GGCCTTTTCTGGCACCGCAGTTTTGTTTTAAAACTGGACCTGTATATTTGTAAAGCT 
               
               
                   
                   
                 ATTTATGGGCCCCTGGCACTCTTGTTCCCACACCCCAACACTTCCAGCATTTAGCTG 
               
               
                   
                   
                 GCCACATGGCGGAGAGTTTTAATTTTTAACTTATTGACAACCGAGAAGGTTTATCCC 
               
               
                   
                   
                 GCCGATAGAGGGACGGCCAAGAATGTACGTCCAGCCTGCCCCGGAGCTGGAGGATCC 
               
               
                   
                   
                 CCTCCAAGCCTAAAAGGTTGTTAATAGTTGGAGGTGATTCCAGTGAAGATATTTTAT 
               
               
                   
                   
                 TTCCTTTGTCCTTTTTCAGGAGAATTAGATTTCTATAGGATTTTTCTTTAGGAGATT 
               
               
                   
                   
                 TATTTTTTGGACTTCAAAGCAAGCTGGTATTTTCATACAAATTCTTCTAATTGCTGT 
               
               
                   
                   
                 GTGTCCCAGGCAGGGAGACGGTTTCCAGGGAGGGGCCGGCCCTGTGTGCAGGTTCCG 
               
               
                   
                   
                 ATGTTATTAGATGTTACAAGTTTATATATATCTATATATATAATTTATTGAGTTTTT 
               
               
                   
                   
                 ACAAGATGTATTTGTTGTAGACTTAACACTTCTTACGCAATGCTTCTAGAGTTTTAT 
               
               
                   
                   
                 AGCCTGGACTGCTACCTTTCAAAGCTTGGAGGGAAGCCGTGAATTCAGTTGGTTCGT 
               
               
                   
                   
                 TCTGTACTGTTACTGGGCCCTGAGTCTGGGCAGCTGTCCCTTGCTTGCCTGCAGGGC 
               
               
                   
                   
                 CATGGCTCAGGGTGGTCTCTTCTTGGGGCCCAGTGCATGGTGGCCAGAGGTGTCACC 
               
               
                   
                   
                 CAAACCGGCAGGTGCGATTTTGTTAACCCAGCGACGAACTTTCCGAAAAATAAAGAC 
               
               
                   
                   
                 ACCTGGTTGCTAACCTGG 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAV 
               
               
                 NO: 44 
                 isoform 2 
                 ELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLT 
               
               
                   
                 Amino acid 
                 QRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANT 
               
               
                   
                 sequence 
                 VRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTC 
               
               
                   
                   
                 VVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHI 
               
               
                   
                   
                 QWLKHVEVNGSKVGPDGTPYVTVLKSWISESVEADVRLRLANVSERDGGEYLCRATN 
               
               
                   
                   
                 FIGVAEKAFWLSVHGPRAAEEELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCR 
               
               
                   
                   
                 LRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGPTLANV 
               
               
                   
                   
                 SELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLK 
               
               
                   
                   
                 DDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYV LVEYAAKGNLR EFLR 
               
               
                   
                   
                 ARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLV 
               
               
                   
                   
                 TEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGV 
               
               
                   
                   
                 LLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRP 
               
               
                   
                   
                 TFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPP 
               
               
                   
                   
                 APPSSGGSRT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 GTCGCGGGCAGCTGGCGCCGCGCGGTCCTGCTCTGCCGGTCGCACGGACGCACCGGC 
               
               
                 NO: 45 
                 isoform 3 
                 GGGCCGCCGGCCGGAGGGACGGGGCGGGAGCTGGGCCCGCGGACAGCGAGCCGGAGC 
               
               
                   
                 Nucleic acid 
                 GGGAGCCGCGCGTAGCGAGCCGGGCTCCGGCGCTCGCCAGTCTCCCGAGCGGCGCCC 
               
               
                   
                 sequence 
                 GCCTCCCGCCGGTGCCCGCGCCGGGCCGTGGGGGGCAGCATGCCCGCGCGCGCTGCC 
               
               
                   
                   
                 TGAGGACGCCGCGGCCCCCGCCCCCGCCATGGGCGCCCCTGCCTGCGCCCTCGCGCT 
               
               
                   
                   
                 CTGCGTGGCCGTGGCCATCGTGGCCGGCGCCTCCTCGGAGTCCTTGGGGACGGAGCA 
               
               
                   
                   
                 GCGCGTCGTGGGGCGAGCGGCAGAAGTCCCGGGCCCAGAGCCCGGCCAGCAGGAGCA 
               
               
                   
                   
                 GTTGGTCTTCGGCAGCGGGGATGCTGTGGAGCTGAGCTGTCCCCCGCCCGGGGGTGG 
               
               
                   
                   
                 TCCCATGGGGCCCACTGTCTGGGTCAAGGATGGCACAGGGCTGGTGCCCTCGGAGCG 
               
               
                   
                   
                 TGTCCTGGTGGGGCCCCAGCGGCTGCAGGTGCTGAATGCCTCCCACGAGGACTCCGG 
               
               
                   
                   
                 GGCCTACAGCTGCCGGCAGCGGCTCACGCAGCGCGTACTGTGCCACTTCAGTGTGCG 
               
               
                   
                   
                 GGTGACAGACGCTCCATCCTCGGGAGATGACGAAGACGGGGAGGACGAGGCTGAGGA 
               
               
                   
                   
                 CACAGGTGTGGACACAGGGGCCCCTTACTGGACACGGCCCGAGCGGATGGACAAGAA 
               
               
                   
                   
                 GCTGCTGGCCGTGCCGGCCGCCAACACCGTCCGCTTCCGCTGCCCAGCCGCTGGCAA 
               
               
                   
                   
                 CCCCACTCCCTCCATCTCCTGGCTGAAGAACGGCAGGGAGTTCCGCGGCGAGCACCG 
               
               
                   
                   
                 CATTGGAGGCATCAAGCTGCGGCATCAGCAGTGGAGCCTGGTCATGGAAAGCGTGGT 
               
               
                   
                   
                 GCCCTCGGACCGCGGCAACTACACCTGCGTCGTGGAGAACAAGTTTGGCAGCATCCG 
               
               
                   
                   
                 GCAGACGTACACGCTGGACGTGCTGGAGCGCTCCCCGCACCGGCCCATCCTGCAGGC 
               
               
                   
                   
                 GGGGCTGCCGGCCAACCAGACGGCGGTGCTGGGCAGCGACGTGGAGTTCCACTGCAA 
               
               
                   
                   
                 GGTGTACAGTGACGCACAGCCCCACATCCAGTGGCTCAAGCACGTGGAGGTGAATGG 
               
               
                   
                   
                 CAGCAAGGTGGGCCCGGACGGCACACCCTACGTTACCGTGCTCAAGGTGTCCCTGGA 
               
               
                   
                   
                 GTCCAACGCGTCCATGAGCTCCAACACACCACTGGTGCGCATCGCAAGGCTGTCCTC 
               
               
                   
                   
                 AGGGGAGGGCCCCACGCTGGCCAATGTCTCCGAGCTCGAGCTGCCTGCCGACCCCAA 
               
               
                   
                   
                 ATGGGAGCTGTCTCGGGCCCGGCTGACCCTGGGCAAGCCCCTTGGGGAGGGCTGCTT 
               
               
                   
                   
                 CGGCCAGGTGGTCATGGCGGAGGCCATCGGCATTGACAAGGACCGGGCCGCCAAGCC 
               
               
                   
                   
                 TGTCACCGTAGCCGTGAAGATGCTGAAAGACGATGCCACTGACAAGGACCTGTCGGA 
               
               
                   
                   
                 CCTGGTGTCTGAGATGGAGATGATGAAGATGATCGGGAAACACAAAAACATCATCAA 
               
               
                   
                   
                 CCTGCTGGGCGCCTGCACGCAGGGCGGGCCCCTGTACGTGCTGGTGGAGTACGCGGC 
               
               
                   
                   
                 CAAGGGTAACCTGCGGGAGTTTCTGCGGGCGCGGCGGCCCCCGGGCCTGGACTACTC 
               
               
                   
                   
                 CTTCGACACCTGCAAGCCGCCCGAGGAGCAGCTCACCTTCAAGGACCTGGTGTCCTG 
               
               
                   
                   
                 TGCCTACCAGGTGGCCCGGGGCATGGAGTACTTGGCCTCCCAGAAGTGCATCCACAG 
               
               
                   
                   
                 GGACCTGGCTGCCCGCAATGTGCTGGTGACCGAGGACAACGTGATGAAGATCGCAGA 
               
               
                   
                   
                 CTTCGGGCTGGCCCGGGACGTGCACAACCTCGACTACTACAAGAAGACGACCAACGG 
               
               
                   
                   
                 CCGGCTGCCCGTGAAGTGGATGGCGCCTGAGGCCTTGTTTGACCGAGTCTACACTCA 
               
               
                   
                   
                 CCAGAGTGACGTCTGGTCCTTTGGGGTCCTGCTCTGGGAGATCTTCACGCTGGGGGG 
               
               
                   
                   
                 CTCCCCGTACCCCGGCATCCCTGTGGAGGAGCTCTTCAAGCTGCTGAAGGAGGGCCA 
               
               
                   
                   
                 CCGCATGGACAAGCCCGCCAACTGCACACACGACCTGTACATGATCATGCGGGAGTG 
               
               
                   
                   
                 CTGGCATGCCGCGCCCTCCCAGAGGCCCACCTTCAAGCAGCTGGTGGAGGACCTGGA 
               
               
                   
                   
                 CCGTGTCCTTACCGTGACGTCCACCGACGAGTACCTGGACCTGTCGGCGCCTTTCGA 
               
               
                   
                   
                 GCAGTACTCCCCGGGTGGCCAGGACACCCCCAGCTCCAGCTCCTCAGGGGACGACTC 
               
               
                   
                   
                 CGTGTTTGCCCACGACCTGCTGCCCCCGGCCCCACCCAGCAGTGGGGGCTCGCGGAC 
               
               
                   
                   
                 GTGAAGGGCCACTGGTCCCCAACAATGTGAGGGGTCCCTAGCAGCCCACCCTGCTGC 
               
               
                   
                   
                 TGGTGCACAGCCACTCCCCGGCATGAGACTCAGTGCAGATGGAGAGACAGCTACACA 
               
               
                   
                   
                 GAGCTTTGGTCTGTGTGTGTGTGTGTGCGTGTGTGTGTGTGTGTGTGCACATCCGCG 
               
               
                   
                   
                 TGTGCCTGTGTGCGTGCGCATCTTGCCTCCAGGTGCAGAGGTACCCTGGGTGTCCCC 
               
               
                   
                   
                 GCTGCTGTGCAACGGTCTCCTGACTGGTGCTGCAGCACCGAGGGGCCTTTGTTCTGG 
               
               
                   
                   
                 GGGGACCCAGTGCAGAATGTAAGTGGGCCCACCCGGTGGGACCCCCGTGGGGCAGGG 
               
               
                   
                   
                 AGCTGGGCCCGACATGGCTCCGGCCTCTGCCTTTGCACCACGGGACATCACAGGGTG 
               
               
                   
                   
                 GGCCTCGGCCCCTCCCACACCCAAAGCTGAGCCTGCAGGGAAGCCCCACATGTCCAG 
               
               
                   
                   
                 CACCTTGTGCCTGGGGTGTTAGTGGCACCGCCTCCCCACCTCCAGGCTTTCCCACTT 
               
               
                   
                   
                 CCCACCCTGCCCCTCAGAGACTGAAATTACGGGTACCTGAAGATGGGAGCCTTTACC 
               
               
                   
                   
                 TTTTATGCAAAAGGTTTATTCCGGAAACTAGTGTACATTTCTATAAATAGATGCTGT 
               
               
                   
                   
                 GTATATGGTATATATACATATATATATATAACATATATGGAAGAGGAAAAGGCTGGT 
               
               
                   
                   
                 ACAACGGAGGCCTGCGACCCTGGGGGCACAGGAGGCAGGCATGGCCCTGGGCGGGGC 
               
               
                   
                   
                 GTGGGGGGGCGTGGAGGGAGGCCCCAGGGGGTCTCACCCATGCAAGCAGAGGACCAG 
               
               
                   
                   
                 GGCCTTTTCTGGCACCGCAGTTTTGTTTTAAAACTGGACCTGTATATTTGTAAAGCT 
               
               
                   
                   
                 ATTTATGGGCCCCTGGCACTCTTGTTCCCACACCCCAACACTTCCAGCATTTAGCTG 
               
               
                   
                   
                 GCCACATGGCGGAGAGTTTTAATTTTTAACTTATTGACAACCGAGAAGGTTTATCCC 
               
               
                   
                   
                 GCCGATAGAGGGACGGCCAAGAATGTACGTCCAGCCTGCCCCGGAGCTGGAGGATCC 
               
               
                   
                   
                 CCTCCAAGCCTAAAAGGTTGTTAATAGTTGGAGGTGATTCCAGTGAAGATATTTTAT 
               
               
                   
                   
                 TTCCTTTGTCCTTTTTCAGGAGAATTAGATTTCTATAGGATTTTTCTTTAGGAGATT 
               
               
                   
                   
                 TATTTTTTGGACTTCAAAGCAAGCTGGTATTTTCATACAAATTCTTCTAATTGCTGT 
               
               
                   
                   
                 GTGTCCCAGGCAGGGAGACGGTTTCCAGGGAGGGGCCGGCCCTGTGTGCAGGTTCCG 
               
               
                   
                   
                 ATGTTATTAGATGTTACAAGTTTATATATATCTATATATATAATTTATTGAGTTTTT 
               
               
                   
                   
                 ACAAGATGTATTTGTTGTAGACTTAACACTTCTTACGCAATGCTTCTAGAGTTTTAT 
               
               
                   
                   
                 AGCCTGGACTGCTACCTTTCAAAGCTTGGAGGGAAGCCGTGAATTCAGTTGGTTCGT 
               
               
                   
                   
                 TCTGTACTGTTACTGGGCCCTGAGTCTGGGCAGCTGTCCCTTGCTTGCCTGCAGGGC 
               
               
                   
                   
                 CATGGCTCAGGGTGGTCTCTTCTTGGGGCCCAGTGCATGGTGGCCAGAGGTGTCACC 
               
               
                   
                   
                 CAAACCGGCAGGTGCGATTTTGTTAACCCAGCGACGAACTTTCCGAAAAATAAAGAC 
               
               
                   
                   
                 ACCTGGTTGCTAACCTGG 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAV 
               
               
                 NO: 46 
                 isoform 3 
                 ELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLT 
               
               
                   
                 Amino acid 
                 QRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANT 
               
               
                   
                 sequence 
                 VRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTC 
               
               
                   
                   
                 VVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHI 
               
               
                   
                   
                 QWLKHVEVNGSKVGPDGTPYVTVLKVSLESNASMSSNTPLVRIARLSSGEGPTLANV 
               
               
                   
                   
                 SELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLK 
               
               
                   
                   
                 DDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYV LVEYAAKGNLR EFLR 
               
               
                   
                   
                 ARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLV 
               
               
                   
                   
                 TEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGV 
               
               
                   
                   
                 LLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRP 
               
               
                   
                   
                 TFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPP 
               
               
                   
                   
                 APPSSGGSRT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 CGCGCGCTGCCTGAGGACGCCGCGGCCCCCGCCCCCGCCATGGGCGCCCCTGCCTGC 
               
               
                 NO: 47 
                 isoform 4 
                 GCCCTCGCGCTCTGCGTGGCCGTGGCCATCGTGGCCGGCGCCTCCTCGGAGTCCTTG 
               
               
                   
                 Nucleic acid 
                 GGGACGGAGCAGCGCGTCGTGGGGCGAGCGGCAGAAGTCCCGGGCCCAGAGCCCGGC 
               
               
                   
                 sequence 
                 CAGCAGGAGCAGTTGGTCTTCGGCAGCGGGGATGCTGTGGAGCTGAGCTGTCCCCCG 
               
               
                   
                   
                 CCCGGGGGTGGTCCCATGGGGCCCACTGTCTGGGTCAAGGATGGCACAGGGCTGGTG 
               
               
                   
                   
                 CCCTCGGAGCGTGTCCTGGTGGGGCCCCAGCGGCTGCAGGTGCTGAATGCCTCCCAC 
               
               
                   
                   
                 GAGGACTCCGGGGCCTACAGCTGCCGGCAGCGGCTCACGCAGCGCGTACTGTGCCAC 
               
               
                   
                   
                 TTCAGTGTGCGGGTGACAGACGCTCCATCCTCGGGAGATGACGAAGACGGGGAGGAC 
               
               
                   
                   
                 GAGGCTGAGGACACAGGTGTGGACACAGGGGCCCCTTACTGGACACGGCCCGAGCGG 
               
               
                   
                   
                 ATGGACAAGAAGCTGCTGGCCGTGCCGGCCGCCAACACCGTCCGCTTCCGCTGCCCA 
               
               
                   
                   
                 GCCGCTGGCAACCCCACTCCCTCCATCTCCTGGCTGAAGAACGGCAGGGAGTTCCGC 
               
               
                   
                   
                 GGCGAGCACCGCATTGGAGGCATCAAGCTGCGGCATCAGCAGTGGAGCCTGGTCATG 
               
               
                   
                   
                 GAAAGCGTGGTGCCCTCGGACCGCGGCAACTACACCTGCGTCGTGGAGAACAAGTTT 
               
               
                   
                   
                 GGCAGCATCCGGCAGACGTACACGCTGGACGTGCTGGAGCGCTCCCCGCACCGGCCC 
               
               
                   
                   
                 ATCCTGCAGGCGGGGCTGCCGGCCAACCAGACGGCGGTGCTGGGCAGCGACGTGGAG 
               
               
                   
                   
                 TTCCACTGCAAGGTGTACAGTGACGCACAGCCCCACATCCAGTGGCTCAAGCACGTG 
               
               
                   
                   
                 GAGGTGAATGGCAGCAAGGTGGGCCCGGACGGCACACCCTACGTTACCGTGCTCAAG 
               
               
                   
                   
                 GTGTCCCTGGAGTCCAACGCGTCCATGAGCTCCAACACACCACTGGTGCGCATCGCA 
               
               
                   
                   
                 AGGCTGTCCTCAGGGGAGGGCCCCACGCTGGCCAATGTCTCCGAGCTCGAGCTGCCT 
               
               
                   
                   
                 GCCGACCCCAAATGGGAGCTGTCTCGGGCCCGGCTGACCCTGGGCAAGCCCCTTGGG 
               
               
                   
                   
                 GAGGGCTGCTTCGGCCAGGTGGTCATGGCGGAGGCCATCGGCATTGACAAGGACCGG 
               
               
                   
                   
                 GCCGCCAAGCCTGTCACCGTAGCCGTGAAGATGCTGAAAGACGATGCCACTGACAAG 
               
               
                   
                   
                 GACCTGTCGGACCTGGTGTCTGAGATGGAGATGATGAAGATGATCGGGAAACACAAA 
               
               
                   
                   
                 AACATCATCAACCTGCTGGGCGCCTGCACGCAGGGCGGGCCCCTGTACGTGCTGGTG 
               
               
                   
                   
                 GAGTACGCGGCCAAGGGTAACCTGCGGGAGTTTCTGCGGGCGCGGCGGCCCCCGGGC 
               
               
                   
                   
                 CTGGACTACTCCTTCGACACCTGCAAGCCGCCCGAGGAGCAGCTCACCTTCAAGGAC 
               
               
                   
                   
                 CTGGTGTCCTGTGCCTACCAGGTGGCCCGGGGCATGGAGTACTTGGCCTCCCAGAAG 
               
               
                   
                   
                 TGCATCCACAGGGACCTGGCTGCCCGCAATGTGCTGGTGACCGAGGACAACGTGATG 
               
               
                   
                   
                 AAGATCGCAGACTTCGGGCTGGCCCGGGACGTGCACAACCTCGACTACTACAAGAAG 
               
               
                   
                   
                 ACGACCAACGGCCGGCTGCCCGTGAAGTGGATGGCGCCTGAGGCCTTGTTTGACCGA 
               
               
                   
                   
                 GTCTACACTCACCAGAGTGACGTCTGGTCCTTTGGGGTCCTGCTCTGGGAGATCTTC 
               
               
                   
                   
                 ACGCTGGGGGGCTCCCCGTACCCCGGCATCCCTGTGGAGGAGCTCTTCAAGCTGCTG 
               
               
                   
                   
                 AAGGAGGGCCACCGCATGGACAAGCCCGCCAACTGCACACACGACCTGTACATGATC 
               
               
                   
                   
                 ATGCGGGAGTGCTGGCATGCCGCGCCCTCCCAGAGGCCCACCTTCAAGCAGCTGGTG 
               
               
                   
                   
                 GAGGACCTGGACCGTGTCCTTACCGTGACGTCCACCGACGAGTACCTGGACCTGTCG 
               
               
                   
                   
                 GCGCCTTTCGAGCAGTACTCCCCGGGTGGCCAGGACACCCCCAGCTCCAGCTCCTCA 
               
               
                   
                   
                 GGGGACGACTCCGTGTTTGCCCACGACCTGCTGCCCCCGGCCCCACCCAGCAGTGGG 
               
               
                   
                   
                 GGCTCGCGGACGTGAAGGGCCACTGGTCCCCAACAATGTGAGGGGTCCCTAGCAGCC 
               
               
                   
                   
                 CACCCTGCTGCTGGTGCA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAV 
               
               
                 NO: 48 
                 isoform 4 
                 ELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLT 
               
               
                   
                 Amino acid 
                 QRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANT 
               
               
                   
                 sequence 
                 VRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTC 
               
               
                   
                   
                 VVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHI 
               
               
                   
                   
                 QWLKHVEVNGSKVGPDGTPYVTVLKVSLESNASMSSNTPLVRIARLSSGEGPTLANV 
               
               
                   
                   
                 SELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRAAKPVTVAVKMLK 
               
               
                   
                   
                 DDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYV LVEYAAKGNLR EFLR 
               
               
                   
                   
                 ARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLV 
               
               
                   
                   
                 TEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGV 
               
               
                   
                   
                 LLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRP 
               
               
                   
                   
                 TFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPP 
               
               
                   
                   
                 APPSSGGSRT 
               
               
                   
               
               
                 SEQ ID 
                 FGFRA 
                 CGCTCGCGGCCACGCCGCCGTCGCGGGTACATTCCTCGCTCCCGGCCGAGGAGCGCT 
               
               
                 NO: 49 
                 isoform 1 
                 CGGGCTGTCTGCGGACCCTGCCGCGTGCAGGGGTCGCGGCCGGCTGGAGCTGGGAGT 
               
               
                   
                 Nucleic acid 
                 GAGGCGGCGGAGGAGCCAGGTGAGGAGGAGCCAGGTGAGCAGGACCCTGTGCTGGGC 
               
               
                   
                 sequence 
                 GCGGAGTCACGCAGGCTCGAGGAAGGCAGTTGGTGGGAAGTCCAGCTTGGGTCCCTG 
               
               
                   
                   
                 AGAGCTGTGAGAAGGAGATGCGGCTGCTGCTGGCCCTGTTGGGGGTCCTGCTGAGTG 
               
               
                   
                   
                 TGCCTGGGCCTCCAGTCTTGTCCCTGGAGGCCTCTGAGGAAGTGGAGCTTGAGCCCT 
               
               
                   
                   
                 GCCTGGCTCCCAGCCTGGAGCAGCAAGAGCAGGAGCTGACAGTAGCCCTTGGGCAGC 
               
               
                   
                   
                 CTGTGCGTCTGTGCTGTGGGCGGGCTGAGCGTGGTGGCCACTGGTACAAGGAGGGCA 
               
               
                   
                   
                 GTCGCCTGGCACCTGCTGGCCGTGTACGGGGCTGGAGGGGCCGCCTAGAGATTGCCA 
               
               
                   
                   
                 GCTTCCTACCTGAGGATGCTGGCCGCTACCTCTGCCTGGCACGAGGCTCCATGATCG 
               
               
                   
                   
                 TCCTGCAGAATCTCACCTTGATTACAGGTGACTCCTTGACCTCCAGCAACGATGATG 
               
               
                   
                   
                 AGGACCCCAAGTCCCATAGGGACCCCTCGAATAGGCACAGTTACCCCCAGCAAGCAC 
               
               
                   
                   
                 CCTACTGGACACACCCCCAGCGCATGGAGAAGAAACTGCATGCAGTACCTGCGGGGA 
               
               
                   
                   
                 ACACCGTCAAGTTCCGCTGTCCAGCTGCAGGCAACCCCACGCCCACCATCCGCTGGC 
               
               
                   
                   
                 TTAAGGATGGACAGGCCTTTCATGGGGAGAACCGCATTGGAGGCATTCGGCTGCGCC 
               
               
                   
                   
                 ATCAGCACTGGAGTCTCGTGATGGAGAGCGTGGTGCCCTCGGACCGCGGCACATACA 
               
               
                   
                   
                 CCTGCCTGGTAGAGAACGCTGTGGGCAGCATCCGCTATAACTACCTGCTAGATGTGC 
               
               
                   
                   
                 TGGAGCGGTCCCCGCACCGGCCCATCCTGCAGGCCGGGCTCCCGGCCAACACCACAG 
               
               
                   
                   
                 CCGTGGTGGGCAGCGACGTGGAGCTGCTGTGCAAGGTGTACAGCGATGCCCAGCCCC 
               
               
                   
                   
                 ACATCCAGTGGCTGAAGCACATCGTCATCAACGGCAGCAGCTTCGGAGCCGACGGTT 
               
               
                   
                   
                 TCCCCTATGTGCAAGTCCTAAAGACTGCAGACATCAATAGCTCAGAGGTGGAGGTCC 
               
               
                   
                   
                 TGTACCTGCGGAACGTGTCAGCCGAGGACGCAGGCGAGTACACCTGCCTCGCAGGCA 
               
               
                   
                   
                 ATTCCATCGGCCTCTCCTACCAGTCTGCCTGGCTCACGGTGCTGCCAGAGGAGGACC 
               
               
                   
                   
                 CCACATGGACCGCAGCAGCGCCCGAGGCCAGGTATACGGACATCATCCTGTACGCGT 
               
               
                   
                   
                 CGGGCTCCCTGGCCTTGGCTGTGCTCCTGCTGCTGGCCGGGCTGTATCGAGGGCAGG 
               
               
                   
                   
                 CGCTCCACGGCCGGCACCCCCGCCCGCCCGCCACTGTGCAGAAGCTCTCCCGCTTCC 
               
               
                   
                   
                 CTCTGGCCCGACAGTTCTCCCTGGAGTCAGGCTCTTCCGGCAAGTCAAGCTCATCCC 
               
               
                   
                   
                 TGGTACGAGGCGTGCGTCTCTCCTCCAGCGGCCCCGCCTTGCTCGCCGGCCTCGTGA 
               
               
                   
                   
                 GTCTAGATCTACCTCTCGACCCACTATGGGAGTTCCCCCGGGACAGGCTGGTGCTTG 
               
               
                   
                   
                 GGAAGCCCCTAGGCGAGGGCTGCTTTGGCCAGGTAGTACGTGCAGAGGCCTTTGGCA 
               
               
                   
                   
                 TGGACCCTGCCCGGCCTGACCAAGCCAGCACTGTGGCCGTCAAGATGCTCAAAGACA 
               
               
                   
                   
                 ACGCCTCTGACAAGGACCTGGCCGACCTGGTCTCGGAGATGGAGGTGATGAAGCTGA 
               
               
                   
                   
                 TCGGCCGACACAAGAACATCATCAACCTGCTTGGTGTCTGCACCCAGGAAGGGCCCC 
               
               
                   
                   
                 TGTACGTGATCGTGGAGTGCGCCGCCAAGGGAAACCTGCGGGAGTTCCTGCGGGCCC 
               
               
                   
                   
                 GGCGCCCCCCAGGCCCCGACCTCAGCCCCGACGGTCCTCGGAGCAGTGAGGGGCCGC 
               
               
                   
                   
                 TCTCCTTCCCAGTCCTGGTCTCCTGCGCCTACCAGGTGGCCCGAGGCATGCAGTATC 
               
               
                   
                   
                 TGGAGTCCCGGAAGTGTATCCACCGGGACCTGGCTGCCCGCAATGTGCTGGTGACTG 
               
               
                   
                   
                 AGGACAATGTGATGAAGATTGCTGACTTTGGGCTGGCCCGCGGCGTCCACCACATTG 
               
               
                   
                   
                 ACTACTATAAGAAAACCAGCAACGGCCGCCTGCCTGTGAAGTGGATGGCGCCCGAGG 
               
               
                   
                   
                 CCTTGTTTGACCGGGTGTACACACACCAGAGTGACGTGTGGTCTTTTGGGATCCTGC 
               
               
                   
                   
                 TATGGGAGATCTTCACCCTCGGGGGCTCCCCGTATCCTGGCATCCCGGTGGAGGAGC 
               
               
                   
                   
                 TGTTCTCGCTGCTGCGGGAGGGACATCGGATGGACCGACCCCCACACTGCCCCCCAG 
               
               
                   
                   
                 AGCTGTACGGGCTGATGCGTGAGTGCTGGCACGCAGCGCCCTCCCAGAGGCCTACCT 
               
               
                   
                   
                 TCAAGCAGCTGGTGGAGGCGCTGGACAAGGTCCTGCTGGCCGTCTCTGAGGAGTACC 
               
               
                   
                   
                 TCGACCTCCGCCTGACCTTCGGACCCTATTCCCCCTCTGGTGGGGACGCCAGCAGCA 
               
               
                   
                   
                 CCTGCTCCTCCAGCGATTCTGTCTTCAGCCACGACCCCCTGCCATTGGGATCCAGCT 
               
               
                   
                   
                 CCTTCCCCTTCGGGTCTGGGGTGCAGACATGAGCAAGGCTCAAGGCTGTGCAGGCAC 
               
               
                   
                   
                 ATAGGCTGGTGGCCTTGGGCCTTGGGGCTCAGCCACAGCCTGACACAGTGCTCGACC 
               
               
                   
                   
                 TTGATAGCATGGGGCCCCTGGCCCAGAGTTGCTGTGCCGTGTCCAAGGGCCGTGCCC 
               
               
                   
                   
                 TTGCCCTTGGAGCTGCCGTGCCTGTGTCCTGATGGCCCAAATGTCAGGGTTCTGCTC 
               
               
                   
                   
                 GGCTTCTTGGACCTTGGCGCTTAGTCCCCATCCCGGGTTTGGCTGAGCCTGGCTGGA 
               
               
                   
                   
                 GAGCTGCTATGCTAAACCTCCTGCCTCCCAATACCAGCAGGAGGTTCTGGGCCTCTG 
               
               
                   
                   
                 AACCCCCTTTCCCCACACCTCCCCCTGCTGCTGCTGCCCCAGCGTCTTGACGGGAGC 
               
               
                   
                   
                 ATTGGCCCCTGAGCCCAGAGAAGCTGGAAGCCTGCCGAAAACAGGAGCAAATGGCGT 
               
               
                   
                   
                 TTTATAAATTATTTTTTTGAAATAAAGCTCTGTGTGCCTGGGTC 
               
               
                   
               
               
                 SEQ ID 
                 FGFRA 
                 MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCC 
               
               
                 NO: 50 
                 isoform 1 
                 GRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLT 
               
               
                   
                 Amino acid 
                 LITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFR 
               
               
                   
                 sequence 
                 CPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVEN 
               
               
                   
                   
                 AVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLK 
               
               
                   
                   
                 HIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLS 
               
               
                   
                   
                 YQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRH 
               
               
                   
                   
                 PRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPL 
               
               
                   
                   
                 DPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKD 
               
               
                   
                   
                 LADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYV IVE     C     AAKGNLR EFLRARRPPGP 
               
               
                   
                   
                 DLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMK 
               
               
                   
                   
                 IADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFT 
               
               
                   
                   
                 LGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVE 
               
               
                   
                   
                 ALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGS 
               
               
                   
                   
                 GVQT 
               
               
                   
               
               
                 SEQ ID 
                 FGFRA 
                 GTCGCGGGTACATTCCTCGCTCCCGGCCGAGGAGCGCTCGGGCTGTCTGCGGACCCT 
               
               
                 NO: 51 
                 isoform 2 
                 GCCGCGTGCAGGGGTCGCGGCCGGCTGGAGCTGGGAGTGAGGCGGCGGAGGAGCCAG 
               
               
                   
                 Nucleic acid 
                 GTGAGGAGGAGCCAGGAAGGCAGTTGGTGGGAAGTCCAGCTTGGGTCCCTGAGAGCT 
               
               
                   
                 sequence 
                 GTGAGAAGGAGATGCGGCTGCTGCTGGCCCTGTTGGGGGTCCTGCTGAGTGTGCCTG 
               
               
                   
                   
                 GGCCTCCAGTCTTGTCCCTGGAGGCCTCTGAGGAAGTGGAGCTTGAGCCCTGCCTGG 
               
               
                   
                   
                 CTCCCAGCCTGGAGCAGCAAGAGCAGGAGCTGACAGTAGCCCTTGGGCAGCCTGTGC 
               
               
                   
                   
                 GTCTGTGCTGTGGGCGGGCTGAGCGTGGTGGCCACTGGTACAAGGAGGGCAGTCGCC 
               
               
                   
                   
                 TGGCACCTGCTGGCCGTGTACGGGGCTGGAGGGGCCGCCTAGAGATTGCCAGCTTCC 
               
               
                   
                   
                 TACCTGAGGATGCTGGCCGCTACCTCTGCCTGGCACGAGGCTCCATGATCGTCCTGC 
               
               
                   
                   
                 AGAATCTCACCTTGATTACAGGTGACTCCTTGACCTCCAGCAACGATGATGAGGACC 
               
               
                   
                   
                 CCAAGTCCCATAGGGACCCCTCGAATAGGCACAGTTACCCCCAGCAAGCACCCTACT 
               
               
                   
                   
                 GGACACACCCCCAGCGCATGGAGAAGAAACTGCATGCAGTACCTGCGGGGAACACCG 
               
               
                   
                   
                 TCAAGTTCCGCTGTCCAGCTGCAGGCAACCCCACGCCCACCATCCGCTGGCTTAAGG 
               
               
                   
                   
                 ATGGACAGGCCTTTCATGGGGAGAACCGCATTGGAGGCATTCGGCTGCGCCATCAGC 
               
               
                   
                   
                 ACTGGAGTCTCGTGATGGAGAGCGTGGTGCCCTCGGACCGCGGCACATACACCTGCC 
               
               
                   
                   
                 TGGTAGAGAACGCTGTGGGCAGCATCCGCTATAACTACCTGCTAGATGTGCTGGAGC 
               
               
                   
                   
                 GGTCCCCGCACCGGCCCATCCTGCAGGCCGGGCTCCCGGCCAACACCACAGCCGTGG 
               
               
                   
                   
                 TGGGCAGCGACGTGGAGCTGCTGTGCAAGGTGTACAGCGATGCCCAGCCCCACATCC 
               
               
                   
                   
                 AGTGGCTGAAGCACATCGTCATCAACGGCAGCAGCTTCGGAGCCGACGGTTTCCCCT 
               
               
                   
                   
                 ATGTGCAAGTCCTAAAGACTGCAGACATCAATAGCTCAGAGGTGGAGGTCCTGTACC 
               
               
                   
                   
                 TGCGGAACGTGTCAGCCGAGGACGCAGGCGAGTACACCTGCCTCGCAGGCAATTCCA 
               
               
                   
                   
                 TCGGCCTCTCCTACCAGTCTGCCTGGCTCACGGTGCTGCCAGAGGAGGACCCCACAT 
               
               
                   
                   
                 GGACCGCAGCAGCGCCCGAGGCCAGTTCTCCCTGGAGTCAGGCTCTTCCGGCAAGTC 
               
               
                   
                   
                 AAGCTCATCCCTGGTACGAGGCGTGCGTCTCTCCTCCAGCGGCCCCGCCTTGCTCGC 
               
               
                   
                   
                 CGGCCTCGCTGGTGCTTGGGAAGCCCCTAGGCGAGGGCTGCTTTGGCCAGGTAGTAC 
               
               
                   
                   
                 GTGCAGAGGCCTTTGGCATGGACCCTGCCCGGCCTGACCAAGCCAGCACTGTGGCCG 
               
               
                   
                   
                 TCAAGATGCTCAAAGACAACGCCTCTGACAAGGACCTGGCCGACCTGGTCTCGGAGA 
               
               
                   
                   
                 TGGAGGTGATGAAGCTGATCGGCCGACACAAGAACATCATCAACCTGCTTGGTGTCT 
               
               
                   
                   
                 GCACCCAGGAAGGGCCCCTGTACGTGATCGTGGAGTGCGCCGCCAAGGGAAACCTGC 
               
               
                   
                   
                 GGGAGTTCCTGCGGGCCCGGCGCCCCCCAGGCCCCGACCTCAGCCCCGACGGTCCTC 
               
               
                   
                   
                 GGAGCAGTGAGGGGCCGCTCTCCTTCCCAGTCCTGGTCTCCTGCGCCTACCAGGTGG 
               
               
                   
                   
                 CCCGAGGCATGCAGTATCTGGAGTCCCGGAAGTGTATCCACCGGGACCTGGCTGCCC 
               
               
                   
                   
                 GCAATGTGCTGGTGACTGAGGACAATGTGATGAAGATTGCTGACTTTGGGCTGGCCC 
               
               
                   
                   
                 GCGGCGTCCACCACATTGACTACTATAAGAAAACCAGCAACGGCCGCCTGCCTGTGA 
               
               
                   
                   
                 AGTGGATGGCGCCCGAGGCCTTGTTTGACCGGGTGTACACACACCAGAGTGACGTGT 
               
               
                   
                   
                 GGTCTTTTGGGATCCTGCTATGGGAGATCTTCACCCTCGGGGGCTCCCCGTATCCTG 
               
               
                   
                   
                 GCATCCCGGTGGAGGAGCTGTTCTCGCTGCTGCGGGAGGGACATCGGATGGACCGAC 
               
               
                   
                   
                 CCCCACACTGCCCCCCAGAGCTGTACGGGCTGATGCGTGAGTGCTGGCACGCAGCGC 
               
               
                   
                   
                 CCTCCCAGAGGCCTACCTTCAAGCAGCTGGTGGAGGCGCTGGACAAGGTCCTGCTGG 
               
               
                   
                   
                 CCGTCTCTGAGGAGTACCTCGACCTCCGCCTGACCTTCGGACCCTATTCCCCCTCTG 
               
               
                   
                   
                 GTGGGGACGCCAGCAGCACCTGCTCCTCCAGCGATTCTGTCTTCAGCCACGACCCCC 
               
               
                   
                   
                 TGCCATTGGGATCCAGCTCCTTCCCCTTCGGGTCTGGGGTGCAGACATGAGCAAGGC 
               
               
                   
                   
                 TCAAGGCTGTGCAGGCACATAGGCTGGTGGCCTTGGGCCTTGGGGCTCAGCCACAGC 
               
               
                   
                   
                 CTGACACAGTGCTCGACCTTGATAGCATGGGGCCCCTGGCCCAGAGTTGCTGTGCCG 
               
               
                   
                   
                 TGTCCAAGGGCCGTGCCCTTGCCCTTGGAGCTGCCGTGCCTGTGTCCTGATGGCCCA 
               
               
                   
                   
                 AATGTCAGGGTTCTGCTCGGCTTCTTGGACCTTGGCGCTTAGTCCCCATCCCGGGTT 
               
               
                   
                   
                 TGGCTGAGCCTGGCTGGAGAGCTGCTATGCTAAACCTCCTGCCTCCCAATACCAGCA 
               
               
                   
                   
                 GGAGGTTCTGGGCCTCTGAACCCCCTTTCCCCACACCTCCCCCTGCTGCTGCTG 
               
               
                   
               
               
                 SEQ ID 
                 FGFR4 
                 MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCC 
               
               
                 NO: 52 
                 isoform 2 
                 GRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLT 
               
               
                   
                 Amino acid 
                 LITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFR 
               
               
                   
                 sequence 
                 CPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVEN 
               
               
                   
                   
                 AVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLK 
               
               
                   
                   
                 HIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLS 
               
               
                   
                   
                 YQSAWLTVLPEEDPTWTAAAPEASSPWSQALPASQAHPWYEACVSPPAAPPCSPASL 
               
               
                   
                   
                 VLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVM 
               
               
                   
                   
                 KLIGRHKNIINLLGVCTQEGPLYV IVE     C     AAKGNLR EFLRARRPPGPDLSPDGPRSSE 
               
               
                   
                   
                 GPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVH 
               
               
                   
                   
                 HIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPV 
               
               
                   
                   
                 EELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSE 
               
               
                   
                   
                 EYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR4 
                 ACATTCCTCGCTCCCGGCCGAGGAGCGCTCGGGCTGTCTGCGGACCCTGCCGCGTGC 
               
               
                 NO: 53 
                 isoform 3 
                 AGGGGTCGCGGCCGGCTGGAGCTGGGAGTGAGGCGGCGGAGGAGCCAGGTGAGGAGG 
               
               
                   
                 Nucleic acid 
                 AGCCAGGAAGGCAGTTGGTGGGAAGTCCAGCTTGGGTCCCTGAGAGCTGTGAGAAGG 
               
               
                   
                 sequence 
                 AGATGCGGCTGCTGCTGGCCCTGTTGGGGGTCCTGCTGAGTGTGCCTGGGCCTCCAG 
               
               
                   
                   
                 TCTTGTCCCTGGAGGCCTCTGAGGAAGTGGAGCTTGAGCCCTGCCTGGCTCCCAGCC 
               
               
                   
                   
                 TGGAGCAGCAAGAGCAGGAGCTGACAGTAGCCCTTGGGCAGCCTGTGCGTCTGTGCT 
               
               
                   
                   
                 GTGGGCGGGCTGAGCGTGGTGGCCACTGGTACAAGGAGGGCAGTCGCCTGGCACCTG 
               
               
                   
                   
                 CTGGCCGTGTACGGGGCTGGAGGGGCCGCCTAGAGATTGCCAGCTTCCTACCTGAGG 
               
               
                   
                   
                 ATGCTGGCCGCTACCTCTGCCTGGCACGAGGCTCCATGATCGTCCTGCAGAATCTCA 
               
               
                   
                   
                 CCTTGATTACAGGTGACTCCTTGACCTCCAGCAACGATGATGAGGACCCCAAGTCCC 
               
               
                   
                   
                 ATAGGGACCCCTCGAATAGGCACAGTTACCCCCAGCAAGCACCCTACTGGACACACC 
               
               
                   
                   
                 CCCAGCGCATGGAGAAGAAACTGCATGCAGTACCTGCGGGGAACACCGTCAAGTTCC 
               
               
                   
                   
                 GCTGTCCAGCTGCAGGCAACCCCACGCCCACCATCCGCTGGCTTAAGGATGGACAGG 
               
               
                   
                   
                 CCTTTCATGGGGAGAACCGCATTGGAGGCATTCGGCTGCGCCATCAGCACTGGAGTC 
               
               
                   
                   
                 TCGTGATGGAGAGCGTGGTGCCCTCGGACCGCGGCACATACACCTGCCTGGTAGAGA 
               
               
                   
                   
                 ACGCTGTGGGCAGCATCCGCTATAACTACCTGCTAGATGTGCTGGAGCGGTCCCCGC 
               
               
                   
                   
                 ACCGGCCCATCCTGCAGGCCGGGCTCCCGGCCAACACCACAGCCGTGGTGGGCAGCG 
               
               
                   
                   
                 ACGTGGAGCTGCTGTGCAAGGTGTACAGCGATGCCCAGCCCCACATCCAGTGGCTGA 
               
               
                   
                   
                 AGCACATCGTCATCAACGGCAGCAGCTTCGGAGCCGACGGTTTCCCCTATGTGCAAG 
               
               
                   
                   
                 TCCTAAAGACTGCAGACATCAATAGCTCAGAGGTGGAGGTCCTGTACCTGCGGAACG 
               
               
                   
                   
                 TGTCAGCCGAGGACGCAGGCGAGTACACCTGCCTCGCAGGCAATTCCATCGGCCTCT 
               
               
                   
                   
                 CCTACCAGTCTGCCTGGCTCACGGTGCTGCCAGAGGAGGACCCCACATGGACCGCAG 
               
               
                   
                   
                 CAGCGCCCGAGGCCAGGTATACGGACATCATCCTGTACGCGTCGGGCTCCCTGGCCT 
               
               
                   
                   
                 TGGCTGTGCTCCTGCTGCTGGCCGGGCTGTATCGAGGGCAGGCGCTCCACGGCCGGC 
               
               
                   
                   
                 ACCCCCGCCCGCCCGCCACTGTGCAGAAGCTCTCCCGCTTCCCTCTGGCCCGACAGT 
               
               
                   
                   
                 TCTCCCTGGAGTCAGGCTCTTCCGGCAAGTCAAGCTCATCCCTGGTACGAGGCGTGC 
               
               
                   
                   
                 GTCTCTCCTCCAGCGGCCCCGCCTTGCTCGCCGGCCTCGTGAGTCTAGATCTACCTC 
               
               
                   
                   
                 TCGACCCACTATGGGAGTTCCCCCGGGACAGGCTGGTGCTTGGGAAGCCCCTAGGCG 
               
               
                   
                   
                 AGGGCTGCTTTGGCCAGGTAGTACGTGCAGAGGCCTTTGGCATGGACCCTGCCCGGC 
               
               
                   
                   
                 CTGACCAAGCCAGCACTGTGGCCGTCAAGATGCTCAAAGACAACGCCTCTGACAAGG 
               
               
                   
                   
                 ACCTGGCCGACCTGGTCTCGGAGATGGAGGTGATGAAGCTGATCGGCCGACACAAGA 
               
               
                   
                   
                 ACATCATCAACCTGCTTGGTGTCTGCACCCAGGAAGGGCCCCTGTACGTGATCGTGG 
               
               
                   
                   
                 AGTGCGCCGCCAAGGGAAACCTGCGGGAGTTCCTGCGGGCCCGGCGCCCCCCAGGCC 
               
               
                   
                   
                 CCGACCTCAGCCCCGACGGTCCTCGGAGCAGTGAGGGGCCGCTCTCCTTCCCAGTCC 
               
               
                   
                   
                 TGGTCTCCTGCGCCTACCAGGTGGCCCGAGGCATGCAGTATCTGGAGTCCCGGAAGT 
               
               
                   
                   
                 GTATCCACCGGGACCTGGCTGCCCGCAATGTGCTGGTGACTGAGGACAATGTGATGA 
               
               
                   
                   
                 AGATTGCTGACTTTGGGCTGGCCCGCGGCGTCCACCACATTGACTACTATAAGAAAA 
               
               
                   
                   
                 CCAGCAACGGCCGCCTGCCTGTGAAGTGGATGGCGCCCGAGGCCTTGTTTGACCGGG 
               
               
                   
                   
                 TGTACACACACCAGAGTGACGTGTGGTCTTTTGGGATCCTGCTATGGGAGATCTTCA 
               
               
                   
                   
                 CCCTCGGGGGCTCCCCGTATCCTGGCATCCCGGTGGAGGAGCTGTTCTCGCTGCTGC 
               
               
                   
                   
                 GGGAGGGACATCGGATGGACCGACCCCCACACTGCCCCCCAGAGCTGTACGGGCTGA 
               
               
                   
                   
                 TGCGTGAGTGCTGGCACGCAGCGCCCTCCCAGAGGCCTACCTTCAAGCAGCTGGTGG 
               
               
                   
                   
                 AGGCGCTGGACAAGGTCCTGCTGGCCGTCTCTGAGGAGTACCTCGACCTCCGCCTGA 
               
               
                   
                   
                 CCTTCGGACCCTATTCCCCCTCTGGTGGGGACGCCAGCAGCACCTGCTCCTCCAGCG 
               
               
                   
                   
                 ATTCTGTCTTCAGCCACGACCCCCTGCCATTGGGATCCAGCTCCTTCCCCTTCGGGT 
               
               
                   
                   
                 CTGGGGTGCAGACATGAGCAAGGCTCAAGGCTGTGCAGGCACATAGGCTGGTGGCCT 
               
               
                   
                   
                 TGGGCCTTGGGGCTCA 
               
               
                   
               
               
                 SEQ ID 
                 FGFR4 
                 MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCC 
               
               
                 NO: 54 
                 isoform 3 
                 GRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLT 
               
               
                   
                 Amino acid 
                 LITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFR 
               
               
                   
                 sequence 
                 CPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVEN 
               
               
                   
                   
                 AVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLK 
               
               
                   
                   
                 HIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLS 
               
               
                   
                   
                 YQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRH 
               
               
                   
                   
                 PRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPL 
               
               
                   
                   
                 DPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKD 
               
               
                   
                   
                 LADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYV IVE     C     AAKGNLR EFLRARRPPGP 
               
               
                   
                   
                 DLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMK 
               
               
                   
                   
                 IADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFT 
               
               
                   
                   
                 LGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVE 
               
               
                   
                   
                 ALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGS 
               
               
                   
                   
                 GVQT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR4 
                 AGTCCAGCTTGGGTCCCTGAGAGCTGTGAGAAGGAGATGCGGCTGCTGCTGGCCCTG 
               
               
                 NO: 55 
                 isoform 4 
                 TTGGGGGTCCTGCTGAGTGTGCCTGGGCCTCCAGTCTTGTCCCTGGAGGCCTCTGAG 
               
               
                   
                 Nucleic acid 
                 GAAGTGGAGCTTGAGCCCTGCCTGGCTCCCAGCCTGGAGCAGCAAGAGCAGGAGCTG 
               
               
                   
                 sequence 
                 ACAGTAGCCCTTGGGCAGCCTGTGCGTCTGTGCTGTGGGCGGGCTGAGCGTGGTGGC 
               
               
                   
                   
                 CACTGGTACAAGGAGGGCAGTCGCCTGGCACCTGCTGGCCGTGTACGGGGCTGGAGG 
               
               
                   
                   
                 GGCCGCCTAGAGATTGCCAGCTTCCTACCTGAGGATGCTGGCCGCTACCTCTGCCTG 
               
               
                   
                   
                 GCACGAGGCTCCATGATCGTCCTGCAGAATCTCACCTTGATTACAGGTGACTCCTTG 
               
               
                   
                   
                 ACCTCCAGCAACGATGATGAGGACCCCAAGTCCCATAGGGACCCCTCGAATAGGCAC 
               
               
                   
                   
                 AGTTACCCCCAGCAAGCACCCTACTGGACACACCCCCAGCGCATGGAGAAGAAACTG 
               
               
                   
                   
                 CATGCAGTACCTGCGGGGAACACCGTCAAGTTCCGCTGTCCAGCTGCAGGCAACCCC 
               
               
                   
                   
                 ACGCCCACCATCCGCTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCGCATT 
               
               
                   
                   
                 GGAGGCATTCGGCTGCGCCATCAGCACTGGAGTCTCGTGATGGAGAGCGTGGTGCCC 
               
               
                   
                   
                 TCGGACCGCGGCACATACACCTGCCTGGTAGAGAACGCTGTGGGCAGCATCCGCTAT 
               
               
                   
                   
                 AACTACCTGCTAGATGTGCTGGAGCGGTCCCCGCACCGGCCCATCCTGCAGGCCGGG 
               
               
                   
                   
                 CTCCCGGCCAACACCACAGCCGTGGTGGGCAGCGACGTGGAGCTGCTGTGCAAGGTG 
               
               
                   
                   
                 TACAGCGATGCCCAGCCCCACATCCAGTGGCTGAAGCACATCGTCATCAACGGCAGC 
               
               
                   
                   
                 AGCTTCGGAGCCGACGGTTTCCCCTATGTGCAAGTCCTAAAGACTGCAGACATCAAT 
               
               
                   
                   
                 AGCTCAGAGGTGGAGGTCCTGTACCTGCGGAACGTGTCAGCCGAGGACGCAGGCGAG 
               
               
                   
                   
                 TACACCTGCCTCGCAGGCAATTCCATCGGCCTCTCCTACCAGTCTGCCTGGCTCACG 
               
               
                   
                   
                 GTGCTGCCAGGTACTGGGCGCATCCCCCACCTCACATGTGACAGCCTGACTCCAGCA 
               
               
                   
                   
                 GGCAGAACCAAGTCTCCCACTTTGCAGTTCTCCCTGGAGTCAGGCTCTTCCGGCAAG 
               
               
                   
                   
                 TCAAGCTCATCCCTGGTACGAGGCGTGCGTCTCTCCTCCAGCGGCCCCGCCTTGCTC 
               
               
                   
                   
                 GCCGGCCTCGTGAGTCTAGATCTACCTCTCGACCCACTATGGGAGTTCCCCCGGGAC 
               
               
                   
                   
                 AGGCTGGTGCTTGGGAAGCCCCTAGGCGAGGGCTGCTTTGGCCAGGTAGTACGTGCA 
               
               
                   
                   
                 GAGGCCTTTGGCATGGACCCTGCCCGGCCTGACCAAGCCAGCACTGTGGCCGTCAAG 
               
               
                   
                   
                 ATGCTCAAAGACAACGCCTCTGACAAGGACCTGGCCGACCTGGTCTCGGAGATGGAG 
               
               
                   
                   
                 GTGATGAAGCTGATCGGCCGACACAAGAACATCATCAACCTGCTTGGTGTCTGCACC 
               
               
                   
                   
                 CAGGAAGGGCCCCTGTACGTGATCGTGGAGTGCGCCGCCAAGGGAAACCTGCGGGAG 
               
               
                   
                   
                 TTCCTGCGGGCCCGGCGCCCCCCAGGCCCCGACCTCAGCCCCGACGGTCCTCGGAGC 
               
               
                   
                   
                 AGTGAGGGGCCGCTCTCCTTCCCAGTCCTGGTCTCCTGCGCCTACCAGGTGGCCCGA 
               
               
                   
                   
                 GGCATGCAGTATCTGGAGTCCCGGAAGTGTATCCACCGGGACCTGGCTGCCCGCAAT 
               
               
                   
                   
                 GTGCTGGTGACTGAGGACAATGTGATGAAGATTGCTGACTTTGGGCTGGCCCGCGGC 
               
               
                   
                   
                 GTCCACCACATTGACTACTATAAGAAAACCAGCAACGGCCGCCTGCCTGTGAAGTGG 
               
               
                   
                   
                 ATGGCGCCCGAGGCCTTGTTTGACCGGGTGTACACACACCAGAGTGACGTGTGGTCT 
               
               
                   
                   
                 TTTGGGATCCTGCTATGGGAGATCTTCACCCTCGGGGGCTCCCCGTATCCTGGCATC 
               
               
                   
                   
                 CCGGTGGAGGAGCTGTTCTCGCTGCTGCGGGAGGGACATCGGATGGACCGACCCCCA 
               
               
                   
                   
                 CACTGCCCCCCAGAGCTGTACGGGCTGATGCGTGAGTGCTGGCACGCAGCGCCCTCC 
               
               
                   
                   
                 CAGAGGCCTACCTTCAAGCAGCTGGTGGAGGCGCTGGACAAGGTCCTGCTGGCCGTC 
               
               
                   
                   
                 TCTGAGGAGTACCTCGACCTCCGCCTGACCTTCGGACCCTATTCCCCCTCTGGTGGG 
               
               
                   
                   
                 GACGCCAGCAGCACCTGCTCCTCCAGCGATTCTGTCTTCAGCCACGACCCCCTGCCA 
               
               
                   
                   
                 TTGGGATCCAGCTCCTTCCCCTTCGGGTCTGGGGTGCAGACATGAGCAAGGCTCAAG 
               
               
                   
                   
                 GCTGTGCAGGCACATAGGCTGGTGGCCTTGGGCCTTGGGGCTCAGCCACAGCCTGAC 
               
               
                   
                   
                 ACAGTGCTCGACCTTGATAGCATG 
               
               
                   
               
               
                 SEQ ID 
                 FGFRA 
                 MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCC 
               
               
                 NO: 56 
                 isoform 4 
                 GRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLT 
               
               
                   
                 Amino acid 
                 LITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFR 
               
               
                   
                 sequence 
                 CPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVEN 
               
               
                   
                   
                 AVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLK 
               
               
                   
                   
                 HIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLS 
               
               
                   
                   
                 YQSAWLTVLPGTGRIPHLTCDSLTPAGRTKSPTLQFSLESGSSGKSSSSLVRGVRLS 
               
               
                   
                   
                 SSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQ 
               
               
                   
                   
                 ASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYV IVE     C     A   
               
               
                   
                   
                   AKGNLR EFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIH 
               
               
                   
                   
                 RDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYT 
               
               
                   
                   
                 HQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRE 
               
               
                   
                   
                 CWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSV 
               
               
                   
                   
                 FSHDPLPLGSSSFPFGSGVQT 
               
               
                   
               
               
                 SEQ ID 
                 FGFR1 
                 IVEYASKGNLR 
               
               
                 NO: 57 
                 Subdomain V 
                   
               
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                   
               
               
                   
               
               
                 SEQ ID 
                 FGFR2 
                 IVEYASKGNLR 
               
               
                 NO: 58 
                 Subdomain V 
                   
               
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                   
               
               
                   
               
               
                 SEQ ID 
                 FGFR3 
                 LVEYAAKGNLR 
               
               
                 NO: 59 
                 Subdomain V 
                   
               
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                   
               
               
                   
               
               
                 SEQ ID 
                 FGFR4 
                 IVE C AAKGNLR 
               
               
                 NO: 60 
                 Subdomain V 
                   
               
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
               
               
                   
               
               
                 Bold: FGFR subdomain V 
               
               
                 Underlined: Cysteine in FGFR4 subdomain V 
               
            
           
         
       
     
     Although the invention has been described with reference to the above examples, it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims.