lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CCCC4)cc12
InChIKey: DXVZFJFWHBBCDS-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase in HCV genotype 4A infected in HuH7 cells after 40 hrs by Taqman probe based RT-PCR analysis
Measurement: EC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 640.71, ALogP 7.15, HBA 6, HBD 1, PSA 97.44, QED 0.22
Compound (SMILES): CCN1CCCCC1c1nc(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)no1
InChIKey: VYVLFCZOKFCBJQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 529.43, ALogP 6.2, HBA 9, HBD 1, PSA 98.43, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SSNCGXCONZGQSY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 32.36 nM (pChEMBL 7.489999771118164)
Descriptors: MW 509.57, ALogP 4.53, HBA 9, HBD 1, PSA 107.29, QED 0.33
Compound (SMILES): COc1cn(C(CC2(C(F)(F)F)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: PNSIVGGUCOLACI-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 559.93, ALogP 5.66, HBA 6, HBD 2, PSA 121.42, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C#N)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WJQLXQXBPJJDTC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): CCN1CCCCC1c1nc(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)cs1
InChIKey: WVXLPNDNCDLCQW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 544.51, ALogP 7.27, HBA 8, HBD 1, PSA 72.4, QED 0.25
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: MUDOCUNTLILGNS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.02 nM (pChEMBL 7.920000076293945)
Descriptors: MW 486.5, ALogP 4.72, HBA 7, HBD 2, PSA 88.19, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCn2ncnc2C)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: HMOQXJKIXKAECO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 144.54 nM (pChEMBL 6.840000152587891)
Descriptors: MW 512.62, ALogP 4.9, HBA 10, HBD 0, PSA 96.01, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)n(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MVIXBPATNRRIAA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.586 nM (pChEMBL 8.119999885559082)
Descriptors: MW 469.55, ALogP 4.43, HBA 9, HBD 0, PSA 83.12, QED 0.35
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LJSSZFMVOGZNES-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 482.59, ALogP 4.82, HBA 7, HBD 0, PSA 76.38, QED 0.38
Compound (SMILES): N#Cc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: QUQWPSPYENPYJL-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 357.42, ALogP 2.86, HBA 6, HBD 1, PSA 85.9, QED 0.61
Compound (SMILES): COc1ccnc(C#CCN(c2ccc3ncc(-c4cnn(C)c4)nc3c2)c2c(Cl)c(OC)cc(OC)c2Cl)n1
InChIKey: CMWXIQFNVQJMQA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 576.44, ALogP 5.34, HBA 10, HBD 0, PSA 100.31, QED 0.24
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MSSUJWPHHVXXFT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.413 nM (pChEMBL 8.130000114440918)
Descriptors: MW 507.55, ALogP 4.04, HBA 10, HBD 0, PSA 100.31, QED 0.3
Compound (SMILES): COCc1ccc(C(C)=O)c2sc(C(=O)Nc3ccc4c(C(=O)N5CC(OC)C5)cccc4n3)c(C)c12
InChIKey: KHOQORNSGLHMHG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Activity Assay: A human acute lymphoblastic lymphoma T cell line MOLT-4 (which can be purchased under ATCC No. CRL-1582 from ATCC) was cultured in an RPMI1640 medium containing 10% fetal bovine serum to obtain 5108 MOLT-4 cells. The cells were recovered by centrifugation and suspended in 10 ml of buffer solution A (25 mM Tris-HCl, 5 mM 2-mercaptoethanol, 2 mM benzamidine, 2 mM EDTA, and 0.1 mM 4-(2-aminoethyl)benzenesulfonyl hydrochloride, pH 7.5). The cells were homogenized using a Polytron homogenizer and centrifuged (4° C., 25,000 g, 10 minutes). Then, the supernatant was further ultracentrifuged (4° C., 100,000 g, 60 minutes). The obtained supernatant was filtered through a 0.2um filter to obtain a soluble fraction.HiTrap Q HP column (5 ml2, GE Healthcare Japan Corp.) equilibrated with buffer solution A was charged with the obtained soluble fraction. Phosphodiesterase was eluted with 300 ml of buffer solution A containing a linear gradient solution of 0 to 0.8 M NaCl to recover sixty 5-ml fractions. Each fraction was tested for cAMP-metabolizing phosphodiesterase activity. In each fraction, a fraction eluted as an active peak centered around 250 mM NaCl was collected from fractions that had cAMP metabolic activity and did not lose the metabolic activity by 10uM rolipram (PDE4 selective inhibitor) and 10uM milrinone (PDE3 selective inhibitor). In order to confirm whether or not PDE10A mRNA was expressed in the MOLT-4 cells, total RNA was prepared from the MOLT-4 cells according to a standard method and analyzed by RT-PCR using PDE10A gene-specific primers (PDE10A sense primer: 5'-TGCTCCATGGTGGAAGTGGA-3' (SEQ ID NO: 1) and PDE10A antisense primer: 5'-CAACTGGAAGCATGCGGTCA-3' (SEQ ID NO: 2)). As a result, PDE10A mRNA was detected from the total RNA of the MOLT-4 cells. On the other hand, total RNA was prepared from Jurkat cells, one type of human T cell, and similarly subjected to RT-PCR. As a result, PDE10A mRNA was rarely detected. An active peak centered around 250 mM NaCl was not observed in fractions obtained by the treatment of Jurkat cells in the same way as above. Eur J Biochem. 1999, 266 (3), 1118-2 has reported that PDE10A from the rat striatum and testis is eluted as an active peak centered around 250 mM NaCl.
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 517.61, ALogP 4.83, HBA 7, HBD 1, PSA 97.83, QED 0.35
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCO)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: FRFIDSQIINSGEA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.951 nM (pChEMBL 8.529999732971191)
Descriptors: MW 476.54, ALogP 2.78, HBA 9, HBD 2, PSA 114.63, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(S(C)(=O)=O)c4)nc3c2)c1
InChIKey: CNUXPGAXDUDMDQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 479.56, ALogP 3.87, HBA 9, HBD 0, PSA 99.44, QED 0.38
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3cccc(NS(=O)(=O)c4cc(F)ccc4F)c3F)c2c1
InChIKey: WJGKMNJDDJDJHM-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 456.4, ALogP 3.88, HBA 5, HBD 2, PSA 115.71, QED 0.44
Compound (SMILES): COc1cc(OC)c(F)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: UOWDVWIHJKFQPY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 482.54, ALogP 4.46, HBA 8, HBD 1, PSA 77.33, QED 0.38
Compound (SMILES): CC(C)n1cnnc1-c1cccc(N2Cc3ccccc3C2=O)n1
InChIKey: NDBJFFCSTXBTFV-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of ERBB4 (unknown origin)
Measurement: IC50 > 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 319.37, ALogP 3.08, HBA 5, HBD 0, PSA 63.91, QED 0.74
Compound (SMILES): Cl.O=C(CCCN1CCc2ccccc2CC1)c1ccc(Cl)cc1
InChIKey: AXTBQCFVPFLABZ-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H]-pyrilamine from human histamine H1 receptor by liquid scintillation counting method
Measurement: Ki = 1087 nM (pChEMBL 5.960000038146973)
Descriptors: MW 327.86, ALogP 4.4, HBA 2, HBD 0, PSA 20.31, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CCN(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XNZSWBJDMRZZJL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3.236 nM (pChEMBL 8.489999771118164)
Descriptors: MW 432.53, ALogP 3.75, HBA 8, HBD 0, PSA 68.54, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cncn2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WXCQNRFWIHJMLJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.54, ALogP 3.97, HBA 9, HBD 0, PSA 83.12, QED 0.34
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CCCC4)cc12
InChIKey: DXVZFJFWHBBCDS-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase C316Y mutant in HCV genotype 1A infected in HuH7 cells after 40 hrs by Taqman probe based RT-PCR analysis
Measurement: EC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 640.71, ALogP 7.15, HBA 6, HBD 1, PSA 97.44, QED 0.22
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SSNCGXCONZGQSY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 26.92 nM (pChEMBL 7.570000171661377)
Descriptors: MW 509.57, ALogP 4.53, HBA 9, HBD 1, PSA 107.29, QED 0.33
Compound (SMILES): COc1cn(C(CC2(C(F)(F)F)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: PNSIVGGUCOLACI-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 559.93, ALogP 5.66, HBA 6, HBD 2, PSA 121.42, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C#N)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WJQLXQXBPJJDTC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.96 nM (pChEMBL 7.960000038146973)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: MUDOCUNTLILGNS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.248 nM (pChEMBL 8.279999732971191)
Descriptors: MW 486.5, ALogP 4.72, HBA 7, HBD 2, PSA 88.19, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCn2ncnc2C)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: HMOQXJKIXKAECO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 64.57 nM (pChEMBL 7.190000057220459)
Descriptors: MW 512.62, ALogP 4.9, HBA 10, HBD 0, PSA 96.01, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)n(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MVIXBPATNRRIAA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 9.772 nM (pChEMBL 8.010000228881836)
Descriptors: MW 469.55, ALogP 4.43, HBA 9, HBD 0, PSA 83.12, QED 0.35
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LJSSZFMVOGZNES-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 482.59, ALogP 4.82, HBA 7, HBD 0, PSA 76.38, QED 0.38
Compound (SMILES): N#Cc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: QUQWPSPYENPYJL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 357.42, ALogP 2.86, HBA 6, HBD 1, PSA 85.9, QED 0.61
Compound (SMILES): COc1ccnc(C#CCN(c2ccc3ncc(-c4cnn(C)c4)nc3c2)c2c(Cl)c(OC)cc(OC)c2Cl)n1
InChIKey: CMWXIQFNVQJMQA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 20.89 nM (pChEMBL 7.679999828338623)
Descriptors: MW 576.44, ALogP 5.34, HBA 10, HBD 0, PSA 100.31, QED 0.24
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MSSUJWPHHVXXFT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 507.55, ALogP 4.04, HBA 10, HBD 0, PSA 100.31, QED 0.3
Compound (SMILES): COCc1ccc(C(C)=O)c2sc(C(=O)Nc3ccc4c(C(=O)N5CC(OC)C5)cccc4n3)c(C)c12
InChIKey: KHOQORNSGLHMHG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Activity Assay: A human acute lymphoblastic lymphoma T cell line MOLT-4 (which can be purchased under ATCC No. CRL-1582 from ATCC) was cultured in an RPMI1640 medium containing 10% fetal bovine serum to obtain 5108 MOLT-4 cells. The cells were recovered by centrifugation and suspended in 10 ml of buffer solution A (25 mM Tris-HCl, 5 mM 2-mercaptoethanol, 2 mM benzamidine, 2 mM EDTA, and 0.1 mM 4-(2-aminoethyl)benzenesulfonyl hydrochloride, pH 7.5). The cells were homogenized using a Polytron homogenizer and centrifuged (4° C., 25,000 g, 10 minutes). Then, the supernatant was further ultracentrifuged (4° C., 100,000 g, 60 minutes). The obtained supernatant was filtered through a 0.2um filter to obtain a soluble fraction.HiTrap Q HP column (5 ml2, GE Healthcare Japan Corp.) equilibrated with buffer solution A was charged with the obtained soluble fraction. Phosphodiesterase was eluted with 300 ml of buffer solution A containing a linear gradient solution of 0 to 0.8 M NaCl to recover sixty 5-ml fractions. Each fraction was tested for cAMP-metabolizing phosphodiesterase activity. In each fraction, a fraction eluted as an active peak centered around 250 mM NaCl was collected from fractions that had cAMP metabolic activity and did not lose the metabolic activity by 10uM rolipram (PDE4 selective inhibitor) and 10uM milrinone (PDE3 selective inhibitor). In order to confirm whether or not PDE10A mRNA was expressed in the MOLT-4 cells, total RNA was prepared from the MOLT-4 cells according to a standard method and analyzed by RT-PCR using PDE10A gene-specific primers (PDE10A sense primer: 5'-TGCTCCATGGTGGAAGTGGA-3' (SEQ ID NO: 1) and PDE10A antisense primer: 5'-CAACTGGAAGCATGCGGTCA-3' (SEQ ID NO: 2)). As a result, PDE10A mRNA was detected from the total RNA of the MOLT-4 cells. On the other hand, total RNA was prepared from Jurkat cells, one type of human T cell, and similarly subjected to RT-PCR. As a result, PDE10A mRNA was rarely detected. An active peak centered around 250 mM NaCl was not observed in fractions obtained by the treatment of Jurkat cells in the same way as above. Eur J Biochem. 1999, 266 (3), 1118-2 has reported that PDE10A from the rat striatum and testis is eluted as an active peak centered around 250 mM NaCl.
Measurement: IC50 = 0.29 nM (pChEMBL 9.539999961853027)
Descriptors: MW 517.61, ALogP 4.83, HBA 7, HBD 1, PSA 97.83, QED 0.35
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCO)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: FRFIDSQIINSGEA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 0.9772 nM (pChEMBL 9.010000228881836)
Descriptors: MW 476.54, ALogP 2.78, HBA 9, HBD 2, PSA 114.63, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(S(C)(=O)=O)c4)nc3c2)c1
InChIKey: CNUXPGAXDUDMDQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 479.56, ALogP 3.87, HBA 9, HBD 0, PSA 99.44, QED 0.38
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3cccc(NS(=O)(=O)c4cc(F)ccc4F)c3F)c2c1
InChIKey: WJGKMNJDDJDJHM-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.4, ALogP 3.88, HBA 5, HBD 2, PSA 115.71, QED 0.44
Compound (SMILES): COc1cc(OC)c(F)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: UOWDVWIHJKFQPY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.898 nM (pChEMBL 8.3100004196167)
Descriptors: MW 482.54, ALogP 4.46, HBA 8, HBD 1, PSA 77.33, QED 0.38
Compound (SMILES): CC(C)n1cnnc1-c1cccc(N2Cc3ccccc3C2=O)n1
InChIKey: NDBJFFCSTXBTFV-UHFFFAOYSA-N
Target: Ephrin type-A receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P29320
Assay: Inhibition of EPHA3 (unknown origin)
Measurement: IC50 > 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 319.37, ALogP 3.08, HBA 5, HBD 0, PSA 63.91, QED 0.74
Compound (SMILES): Cl.O=C(CCCN1CCc2ccccc2CC1)c1ccc(Cl)cc1
InChIKey: AXTBQCFVPFLABZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D2 receptor by liquid scintillation counting method
Measurement: Ki = 1174.9 nM (pChEMBL 5.929999828338623)
Descriptors: MW 327.86, ALogP 4.4, HBA 2, HBD 0, PSA 20.31, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CCN(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XNZSWBJDMRZZJL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 432.53, ALogP 3.75, HBA 8, HBD 0, PSA 68.54, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cncn2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WXCQNRFWIHJMLJ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.54, ALogP 3.97, HBA 9, HBD 0, PSA 83.12, QED 0.34
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CCCC4)cc12
InChIKey: DXVZFJFWHBBCDS-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase S365A mutant in HCV genotype 1A infected in HuH7 cells after 40 hrs by Taqman probe based RT-PCR analysis
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 640.71, ALogP 7.15, HBA 6, HBD 1, PSA 97.44, QED 0.22
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SSNCGXCONZGQSY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 75.86 nM (pChEMBL 7.119999885559082)
Descriptors: MW 509.57, ALogP 4.53, HBA 9, HBD 1, PSA 107.29, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C#N)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WJQLXQXBPJJDTC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 11.48 nM (pChEMBL 7.940000057220459)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: MUDOCUNTLILGNS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 38.9 nM (pChEMBL 7.409999847412109)
Descriptors: MW 486.5, ALogP 4.72, HBA 7, HBD 2, PSA 88.19, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCn2ncnc2C)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: HMOQXJKIXKAECO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 851.14 nM (pChEMBL 6.070000171661377)
Descriptors: MW 512.62, ALogP 4.9, HBA 10, HBD 0, PSA 96.01, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)n(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MVIXBPATNRRIAA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 107.15 nM (pChEMBL 6.96999979019165)
Descriptors: MW 469.55, ALogP 4.43, HBA 9, HBD 0, PSA 83.12, QED 0.35
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LJSSZFMVOGZNES-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 482.59, ALogP 4.82, HBA 7, HBD 0, PSA 76.38, QED 0.38
Compound (SMILES): N#Cc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: QUQWPSPYENPYJL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 357.42, ALogP 2.86, HBA 6, HBD 1, PSA 85.9, QED 0.61
Compound (SMILES): COc1ccnc(C#CCN(c2ccc3ncc(-c4cnn(C)c4)nc3c2)c2c(Cl)c(OC)cc(OC)c2Cl)n1
InChIKey: CMWXIQFNVQJMQA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 14.79 nM (pChEMBL 7.829999923706055)
Descriptors: MW 576.44, ALogP 5.34, HBA 10, HBD 0, PSA 100.31, QED 0.24
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MSSUJWPHHVXXFT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 10.47 nM (pChEMBL 7.980000019073486)
Descriptors: MW 507.55, ALogP 4.04, HBA 10, HBD 0, PSA 100.31, QED 0.3
Compound (SMILES): CC(CF)Oc1cc(C(=O)NC(C)(CC(N)=O)C2CC2)ncc1C1CC1
InChIKey: FLPDTGMQAJUKQC-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: cAMP Assay: CHO cells expressing human CB1 or CB2 receptors are seeded 17-24 hours prior to the experiment 50.000 cells per well in a black 96 well plate with flat clear bottom (Corning Costar #3904) in DMEM (Invitrogen No. 31331), 1×HT supplement, with 10% fetal calf serum and incubated at 5% CO2 and 37° C. in a humidified incubator. The growth medium was exchanged with Krebs Ringer Bicarbonate buffer with 1 mM IBMX and incubated at 30° C. for 30 min. Compounds were added to a final assay volume of 100 μl and incubated for 30 min at 30° C. Using the cAMP-Nano-TRF detection kit the assay (Roche Diagnostics) was stopped by the addition of 50 μl lysis reagent (Tris, NaCl, 1.5% Triton X100, 2.5% NP40, 10% NaN3) and 50 μl detection solutions (20 μM mAb Alexa700-cAMP 1:1, and 48 μM Ruthenium-2-AHA-cAMP) and shaken for 2 h at room temperature. The time-resolved energy transfer is measured by a TRF reader (Evotec Technologies GmbH), equipped with a ND:YAG laser as excitation source. The plate is measured twice with the excitation at 355 nm and at the emission with a delay of 100 ns and a gate of 100 ns, total exposure time 10 s at 730 (bandwidth 30 nm) or 645 nm (bandwidth 75 nm), respectively. The FRET signal is calculated as follows: FRET=T730-Alexa730-P(T645-B645) with P=Ru730-B730/Ru645-B645, where T730 is the test well measured at 730 nM, T645 is the test well measured at 645 nm, B730 and B645 are the buffer controls at 730 nm and 645 nm, respectively. cAMP content is determined from the function of a standard curve spanning from 10 μM to 0.13 nM cAMP.
Measurement: EC50 = 869 nM (pChEMBL 6.059999942779541)
Descriptors: MW 363.43, ALogP 2.47, HBA 4, HBD 2, PSA 94.31, QED 0.7
Compound (SMILES): COCc1ccc(C(C)=O)c2sc(C(=O)Nc3ccc4c(C(=O)N5CC(OC)C5)cccc4n3)c(C)c12
InChIKey: KHOQORNSGLHMHG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Activity Assay: A human acute lymphoblastic lymphoma T cell line MOLT-4 (which can be purchased under ATCC No. CRL-1582 from ATCC) was cultured in an RPMI1640 medium containing 10% fetal bovine serum to obtain 5108 MOLT-4 cells. The cells were recovered by centrifugation and suspended in 10 ml of buffer solution A (25 mM Tris-HCl, 5 mM 2-mercaptoethanol, 2 mM benzamidine, 2 mM EDTA, and 0.1 mM 4-(2-aminoethyl)benzenesulfonyl hydrochloride, pH 7.5). The cells were homogenized using a Polytron homogenizer and centrifuged (4° C., 25,000 g, 10 minutes). Then, the supernatant was further ultracentrifuged (4° C., 100,000 g, 60 minutes). The obtained supernatant was filtered through a 0.2um filter to obtain a soluble fraction.HiTrap Q HP column (5 ml2, GE Healthcare Japan Corp.) equilibrated with buffer solution A was charged with the obtained soluble fraction. Phosphodiesterase was eluted with 300 ml of buffer solution A containing a linear gradient solution of 0 to 0.8 M NaCl to recover sixty 5-ml fractions. Each fraction was tested for cAMP-metabolizing phosphodiesterase activity. In each fraction, a fraction eluted as an active peak centered around 250 mM NaCl was collected from fractions that had cAMP metabolic activity and did not lose the metabolic activity by 10uM rolipram (PDE4 selective inhibitor) and 10uM milrinone (PDE3 selective inhibitor). In order to confirm whether or not PDE10A mRNA was expressed in the MOLT-4 cells, total RNA was prepared from the MOLT-4 cells according to a standard method and analyzed by RT-PCR using PDE10A gene-specific primers (PDE10A sense primer: 5'-TGCTCCATGGTGGAAGTGGA-3' (SEQ ID NO: 1) and PDE10A antisense primer: 5'-CAACTGGAAGCATGCGGTCA-3' (SEQ ID NO: 2)). As a result, PDE10A mRNA was detected from the total RNA of the MOLT-4 cells. On the other hand, total RNA was prepared from Jurkat cells, one type of human T cell, and similarly subjected to RT-PCR. As a result, PDE10A mRNA was rarely detected. An active peak centered around 250 mM NaCl was not observed in fractions obtained by the treatment of Jurkat cells in the same way as above. Eur J Biochem. 1999, 266 (3), 1118-2 has reported that PDE10A from the rat striatum and testis is eluted as an active peak centered around 250 mM NaCl.
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 517.61, ALogP 4.83, HBA 7, HBD 1, PSA 97.83, QED 0.35
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCO)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: FRFIDSQIINSGEA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.37 nM (pChEMBL 8.270000457763672)
Descriptors: MW 476.54, ALogP 2.78, HBA 9, HBD 2, PSA 114.63, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(S(C)(=O)=O)c4)nc3c2)c1
InChIKey: CNUXPGAXDUDMDQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 467.74 nM (pChEMBL 6.329999923706055)
Descriptors: MW 479.56, ALogP 3.87, HBA 9, HBD 0, PSA 99.44, QED 0.38
Compound (SMILES): COc1cc(OC)c(F)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: UOWDVWIHJKFQPY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 11.22 nM (pChEMBL 7.949999809265137)
Descriptors: MW 482.54, ALogP 4.46, HBA 8, HBD 1, PSA 77.33, QED 0.38
Compound (SMILES): CC(C)n1cnnc1-c1cccc(N2Cc3ccccc3C2=O)n1
InChIKey: NDBJFFCSTXBTFV-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin)
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 319.37, ALogP 3.08, HBA 5, HBD 0, PSA 63.91, QED 0.74
Compound (SMILES): Cl.O=C(CCCN1CCc2ccccc2CC1)c1ccc(Cl)cc1
InChIKey: AXTBQCFVPFLABZ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting method
Measurement: Ki = 107.15 nM (pChEMBL 6.96999979019165)
Descriptors: MW 327.86, ALogP 4.4, HBA 2, HBD 0, PSA 20.31, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CCN(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XNZSWBJDMRZZJL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 89.13 nM (pChEMBL 7.050000190734863)
Descriptors: MW 432.53, ALogP 3.75, HBA 8, HBD 0, PSA 68.54, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cncn2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WXCQNRFWIHJMLJ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.54, ALogP 3.97, HBA 9, HBD 0, PSA 83.12, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SSNCGXCONZGQSY-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 509.57, ALogP 4.53, HBA 9, HBD 1, PSA 107.29, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C#N)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WJQLXQXBPJJDTC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 1659.59 nM (pChEMBL 5.78000020980835)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: MUDOCUNTLILGNS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 134.9 nM (pChEMBL 6.869999885559082)
Descriptors: MW 486.5, ALogP 4.72, HBA 7, HBD 2, PSA 88.19, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCn2ncnc2C)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: HMOQXJKIXKAECO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 512.62, ALogP 4.9, HBA 10, HBD 0, PSA 96.01, QED 0.26
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)n(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MVIXBPATNRRIAA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 245.47 nM (pChEMBL 6.610000133514404)
Descriptors: MW 469.55, ALogP 4.43, HBA 9, HBD 0, PSA 83.12, QED 0.35
Compound (SMILES): COc1cc(C(=O)N2CCCC2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LJSSZFMVOGZNES-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 482.59, ALogP 4.82, HBA 7, HBD 0, PSA 76.38, QED 0.38
Compound (SMILES): COc1ccnc(C#CCN(c2ccc3ncc(-c4cnn(C)c4)nc3c2)c2c(Cl)c(OC)cc(OC)c2Cl)n1
InChIKey: CMWXIQFNVQJMQA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 138.04 nM (pChEMBL 6.860000133514404)
Descriptors: MW 576.44, ALogP 5.34, HBA 10, HBD 0, PSA 100.31, QED 0.24
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2nccc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MSSUJWPHHVXXFT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 602.56 nM (pChEMBL 6.21999979019165)
Descriptors: MW 507.55, ALogP 4.04, HBA 10, HBD 0, PSA 100.31, QED 0.3
Compound (SMILES): CNC(=O)Cn1cc(-c2cnc3ccc(N(CCCO)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: FRFIDSQIINSGEA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 83.18 nM (pChEMBL 7.079999923706055)
Descriptors: MW 476.54, ALogP 2.78, HBA 9, HBD 2, PSA 114.63, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(S(C)(=O)=O)c4)nc3c2)c1
InChIKey: CNUXPGAXDUDMDQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 1819.7 nM (pChEMBL 5.739999771118164)
Descriptors: MW 479.56, ALogP 3.87, HBA 9, HBD 0, PSA 99.44, QED 0.38
Compound (SMILES): COc1cc(OC)c(F)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: UOWDVWIHJKFQPY-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 17.38 nM (pChEMBL 7.760000228881836)
Descriptors: MW 482.54, ALogP 4.46, HBA 8, HBD 1, PSA 77.33, QED 0.38
Compound (SMILES): CC(C)n1cnnc1-c1cccc(N2Cc3ccccc3C2=O)n1
InChIKey: NDBJFFCSTXBTFV-UHFFFAOYSA-N
Target: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13131
Assay: Inhibition of PRKKA1 (unknown origin)
Measurement: IC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 319.37, ALogP 3.08, HBA 5, HBD 0, PSA 63.91, QED 0.74
Compound (SMILES): Cl.O=C(CCCN1CCc2ccccc2CC1)c1ccc(Cl)cc1
InChIKey: AXTBQCFVPFLABZ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30729
Assay: Displacement of [3H]-N-methylspiperone from rat dopamine D4 receptor by liquid scintillation counting method
Measurement: Ki = 81.28 nM (pChEMBL 7.090000152587891)
Descriptors: MW 327.86, ALogP 4.4, HBA 2, HBD 0, PSA 20.31, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CCN(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XNZSWBJDMRZZJL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 432.53, ALogP 3.75, HBA 8, HBD 0, PSA 68.54, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cncn2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WXCQNRFWIHJMLJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.54, ALogP 3.97, HBA 9, HBD 0, PSA 83.12, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SSNCGXCONZGQSY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 912.01 nM (pChEMBL 6.039999961853027)
Descriptors: MW 509.57, ALogP 4.53, HBA 9, HBD 1, PSA 107.29, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C#N)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WJQLXQXBPJJDTC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 6.761 nM (pChEMBL 8.170000076293945)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: MUDOCUNTLILGNS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 436.52 nM (pChEMBL 6.360000133514404)
Descriptors: MW 486.5, ALogP 4.72, HBA 7, HBD 2, PSA 88.19, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CCn2ncnc2C)c2ccc3ncc(-c4cnn(CC(C)C)c4)nc3c2)c1
InChIKey: HMOQXJKIXKAECO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.62, ALogP 4.9, HBA 10, HBD 0, PSA 96.01, QED 0.26