lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCSc2nc(-c3ccc(S(C)(=O)=O)cc3)n(-c3ccc(C(F)(F)F)cc3)n2)cc1OC(C)=O
InChIKey: QDVOVMDRCGSSHA-PJQLUOCWSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P12527
Assay: Inhibition of 5-LOX in Sprague-Dawley rat leukocytes assessed as A23187 stimulated LTB4 production pretreated for 30 mins followed by addition of A23187 for 30 mins by EIA
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 689.69, ALogP 5.56, HBA 12, HBD 0, PSA 143.75, QED 0.06
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCCSc2nc(-c3ccc(S(C)(=O)=O)cc3)n(-c3ccc(Br)cc3)n2)cc1OC(C)=O
InChIKey: NCAJXGYQGGKOJU-OMCISZLKSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P12527
Assay: Inhibition of 5-LOX in Sprague-Dawley rat leukocytes assessed as A23187 stimulated LTB4 production pretreated for 30 mins followed by addition of A23187 for 30 mins by EIA
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 714.62, ALogP 5.69, HBA 12, HBD 0, PSA 143.75, QED 0.06
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCSc2nc(-c3ccc(S(N)(=O)=O)cc3)n(-c3ccc(Br)cc3)n2)cc1OC(C)=O
InChIKey: MRFWDBCFIGASGO-LNKIKWGQSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 701.58, ALogP 4.54, HBA 12, HBD 1, PSA 169.77, QED 0.08
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCSc2nc(-c3ccc(S(N)(=O)=O)cc3)n(-c3ccc(F)cc3)n2)cc1OC(C)=O
InChIKey: BWORMQUAGDJQCG-LNKIKWGQSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 640.67, ALogP 3.92, HBA 12, HBD 1, PSA 169.77, QED 0.08
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCSc2nc(-c3ccc(S(N)(=O)=O)cc3)n(-c3ccccc3)n2)cc1OC(C)=O
InChIKey: RJAVEKISNFNUKD-OQLLNIDSSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 622.68, ALogP 3.78, HBA 12, HBD 1, PSA 169.77, QED 0.08
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCCSc2nc(-c3ccc(S(N)(=O)=O)cc3)n(-c3ccc(F)cc3)n2)cc1OC(C)=O
InChIKey: SVZXXIMBDHIMHF-PJQLUOCWSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 654.7, ALogP 4.31, HBA 12, HBD 1, PSA 169.77, QED 0.08
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)OCCCSc2nc(-c3ccc(S(N)(=O)=O)cc3)n(-c3ccccc3)n2)cc1OC(C)=O
InChIKey: ZRSLTYQNGUAXTK-MHWRWJLKSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 636.71, ALogP 4.17, HBA 12, HBD 1, PSA 169.77, QED 0.08
Compound (SMILES): CS(=O)(=O)c1ccc(-c2nc(SCCOC(=O)/C=C/c3ccc(O)c(O)c3)nn2-c2ccccc2)cc1
InChIKey: ISHRWFHSYGSUJA-RIYZIHGNSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 537.62, ALogP 4.1, HBA 10, HBD 2, PSA 131.61, QED 0.11
Compound (SMILES): CS(=O)(=O)c1ccc(-c2nc(SCCCOC(=O)/C=C/c3ccc(O)c(O)c3)nn2-c2ccc(Br)cc2)cc1
InChIKey: JQXRDICUKMKSEW-LNKIKWGQSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 630.54, ALogP 5.25, HBA 10, HBD 2, PSA 131.61, QED 0.08
Compound (SMILES): CS(=O)(=O)c1ccc(-c2nc(SCCCOC(=O)/C=C/c3ccc(O)c(O)c3)nn2-c2ccc(F)cc2)cc1
InChIKey: DXYAYWHIYCPLTL-LNKIKWGQSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 569.64, ALogP 4.63, HBA 10, HBD 2, PSA 131.61, QED 0.09
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nc(SCCOC(=O)/C=C/c3ccc(O)c(O)c3)nn2-c2ccccc2)cc1
InChIKey: AOJLCKAGSOKLCP-NTUHNPAUSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 538.61, ALogP 3.34, HBA 10, HBD 3, PSA 157.63, QED 0.1
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nc(SCCCOC(=O)/C=C/c3ccc(O)c(O)c3)nn2-c2ccccc2)cc1
InChIKey: CQDKYCVCYZWZRH-RIYZIHGNSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 552.63, ALogP 3.73, HBA 10, HBD 3, PSA 157.63, QED 0.09
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)NCCSc2nc(-c3ccc(S(C)(=O)=O)cc3)n(-c3ccc(F)cc3)n2)cc1OC(C)=O
InChIKey: DOFAPWKNJKOEES-PJQLUOCWSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 638.7, ALogP 4.25, HBA 11, HBD 1, PSA 146.55, QED 0.08
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)NCCCSc2nc(-c3ccc(S(C)(=O)=O)cc3)n(-c3ccc(Br)cc3)n2)cc1OC(C)=O
InChIKey: GTYNQOGINKDAST-OMCISZLKSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 713.63, ALogP 5.26, HBA 11, HBD 1, PSA 146.55, QED 0.07
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)NCCCSc2nc(-c3ccc(S(C)(=O)=O)cc3)n(-c3ccc(F)cc3)n2)cc1OC(C)=O
InChIKey: JGJCEFSNGGQSOF-OMCISZLKSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 652.73, ALogP 4.64, HBA 11, HBD 1, PSA 146.55, QED 0.08
Compound (SMILES): CC(=O)Oc1ccc(/C=C/C(=O)NCCSc2nc(-c3ccc(S(N)(=O)=O)cc3)n(-c3ccc(Br)cc3)n2)cc1OC(C)=O
InChIKey: TYIXEVDIWPISAZ-LNKIKWGQSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35355
Assay: Inhibition of COX2 in rat abdominal macrophages assessed as PGE2 production pretreated for 30 mins followed by addition of 10 uM arachidonic acid as substrate for 20 mins by EIA
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 700.59, ALogP 4.12, HBA 11, HBD 2, PSA 172.57, QED 0.08
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(-n4cc(-c5ccccc5)nn4)nc31)[C@H](O)[C@@H]2O
InChIKey: UMSIUKJTKPZJHN-DHTGQPOCSA-N
Target: Transmembrane domain-containing protein TMIGD3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS9
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyl-uronamide from human adenosine A3 receptor stably expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 0.96 nM (pChEMBL 9.020000457763672)
Descriptors: MW 461.49, ALogP 0.14, HBA 11, HBD 4, PSA 155.9, QED 0.32
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(-n4cc(-c5ccccc5Cl)nn4)nc31)[C@H](O)[C@@H]2O
InChIKey: LLQDFDPAVIHJQU-CKMXMFDLSA-N
Target: Transmembrane domain-containing protein TMIGD3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS9
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyl-uronamide from human adenosine A3 receptor stably expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 0.95 nM (pChEMBL 9.020000457763672)
Descriptors: MW 495.93, ALogP 0.8, HBA 11, HBD 4, PSA 155.9, QED 0.31
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(-n4cc(-c5ccc(F)c(F)c5)nn4)nc31)[C@H](O)[C@@H]2O
InChIKey: AOOMEUGIAVTZCU-RHQIVRABSA-N
Target: Transmembrane domain-containing protein TMIGD3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS9
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyl-uronamide from human adenosine A3 receptor stably expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 497.47, ALogP 0.42, HBA 11, HBD 4, PSA 155.9, QED 0.31
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(-n4cc(-c5ccccn5)nn4)nc31)[C@H](O)[C@@H]2O
InChIKey: BNIPIPFEHPVNHN-ZHIUVZOMSA-N
Target: Transmembrane domain-containing protein TMIGD3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS9
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyl-uronamide from human adenosine A3 receptor stably expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 1.84 nM (pChEMBL 8.729999542236328)
Descriptors: MW 462.47, ALogP -0.46, HBA 12, HBD 4, PSA 168.79, QED 0.3
Compound (SMILES): O=C(/C=C/c1ccc(O)c2c1[C@@H](C(=O)O[C@H](Cc1ccc(O)c(O)c1)C(=O)O)[C@H](c1ccc(O)c(O)c1)O2)O[C@H](Cc1ccc(O)c(O)c1)C(=O)O
InChIKey: SNKFFCBZYFGCQN-PDVBOLEISA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: SARS-CoV-2 3CL-Pro protease inhibition IC50 determined by FRET kind of response from peptide substrate
Measurement: IC50 = 3420 nM (pChEMBL 5.46999979019165)
Descriptors: MW 718.62, ALogP 3.33, HBA 14, HBD 9, PSA 278.04, QED 0.06
Compound (SMILES): Cc1nc(C)c(CNc2nc(CCC#Cc3ccccn3)nc(Cl)c2C)s1
InChIKey: DGFINCOKRZPERW-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 397.94, ALogP 4.5, HBA 6, HBD 1, PSA 63.59, QED 0.51
Compound (SMILES): Cc1nc(C)c(CNc2nc(OCC#Cc3ccccn3)nc(Cl)c2C)s1
InChIKey: QGXVZSSOCCXFBD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 399.91, ALogP 3.95, HBA 7, HBD 1, PSA 72.82, QED 0.52
Compound (SMILES): Cc1nc(C)c(CNc2nc(NCC(C)(C)Cc3ccccn3)nc(Cl)c2C)s1
InChIKey: FKAJGECGZRZOTP-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 431.01, ALogP 5.2, HBA 7, HBD 2, PSA 75.62, QED 0.48
Compound (SMILES): Cc1nc(C)c(CNc2nc(NCCCc3ccccn3)nc(Cl)c2C)s1
InChIKey: YFEVNZSHYJVISN-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 402.96, ALogP 4.56, HBA 7, HBD 2, PSA 75.62, QED 0.42
Compound (SMILES): Cc1nc(C)c(CNc2nc(CCCCc3ccccn3)nc(Cl)c2C)s1
InChIKey: WQJYXOMJIHDJNC-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 401.97, ALogP 5.08, HBA 6, HBD 1, PSA 63.59, QED 0.42
Compound (SMILES): Cc1nc(C)c(CNc2nc(CCCOc3ccccn3)nc(Cl)c2C)s1
InChIKey: VXECAYIGMKDKPM-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 403.94, ALogP 4.53, HBA 7, HBD 1, PSA 72.82, QED 0.44
Compound (SMILES): Cc1nc(C)c(CNc2nc(OCCCc3ccccn3)nc(Cl)c2C)s1
InChIKey: IXPUOLNOFVYFMG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 403.94, ALogP 4.53, HBA 7, HBD 1, PSA 72.82, QED 0.44
Compound (SMILES): Cc1nc(C)c(CNc2nc(OC[C@H]3C[C@H]3c3ccccn3)nc(Cl)c2C)s1
InChIKey: MAFLAYQHEPPOKU-HUUCEWRRSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 415.95, ALogP 4.7, HBA 7, HBD 1, PSA 72.82, QED 0.56
Compound (SMILES): Cc1nc(C)c(CNc2nc(CC[C@H]3C[C@@H]3c3ccccn3)nc(Cl)c2C)s1
InChIKey: MDXQQOOZCSAVOU-HOTGVXAUSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 413.98, ALogP 5.26, HBA 6, HBD 1, PSA 63.59, QED 0.54
Compound (SMILES): Cc1nc(C)c(CNc2nc(OC[C@@H]3C[C@H]3c3ccccn3)nc(Cl)c2C)s1
InChIKey: MAFLAYQHEPPOKU-LSDHHAIUSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 415.95, ALogP 4.7, HBA 7, HBD 1, PSA 72.82, QED 0.56
Compound (SMILES): Cc1ccnc(C2CC2COc2nc(Cl)c(C)c(NCc3sc(C)nc3C)n2)c1
InChIKey: MLOPVEXBAIYYGS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 0.01 nM (pChEMBL 11)
Descriptors: MW 429.98, ALogP 5.01, HBA 7, HBD 1, PSA 72.82, QED 0.53
Compound (SMILES): CN1CCC(C(=O)N2CCC[C@@H](n3nc(-c4ccc(Oc5ccccc5)cc4)c4c(N)ncnc43)C2)CC1
InChIKey: UAHGKVLVIDPPFN-JOCHJYFZSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 421 nM (pChEMBL 6.380000114440918)
Descriptors: MW 511.63, ALogP 4.37, HBA 8, HBD 1, PSA 102.4, QED 0.42
Compound (SMILES): CS(=O)(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: ZSPZCUAATJGYMC-QGZVFWFLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 464.55, ALogP 3.46, HBA 8, HBD 1, PSA 116.23, QED 0.48
Compound (SMILES): NCC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: FOVHNHKLUWEBIJ-QGZVFWFLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 443.51, ALogP 2.99, HBA 8, HBD 2, PSA 125.18, QED 0.49
Compound (SMILES): CN(C)CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: IZNAFSDUTMZGSF-LJQANCHMSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 autophosphorylation at Tyr589/591 residue in human MV4-11 cells for 4 hrs by immunoblot analysis
Measurement: EC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 471.57, ALogP 3.59, HBA 8, HBD 1, PSA 102.4, QED 0.46
Compound (SMILES): C[C@@H](N)C(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: OTEIDYMRWGMHOA-SJLPKXTDSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 457.54, ALogP 3.38, HBA 8, HBD 2, PSA 125.18, QED 0.47
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2[C@@H]1CCCN(C(=O)[C@H](N)CO)C1
InChIKey: CLIPDXMIFFETPP-YLJYHZDGSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 473.54, ALogP 2.35, HBA 9, HBD 3, PSA 145.41, QED 0.39
Compound (SMILES): CC(C)[C@@H](N)C(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: DASBULWGLYMECT-AUSIDOKSSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 485.59, ALogP 4.01, HBA 8, HBD 2, PSA 125.18, QED 0.42
Compound (SMILES): CC(O)[C@@H](N)C(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: INHDKUIENWRTPW-AGVRXMCOSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 487.56, ALogP 2.74, HBA 9, HBD 3, PSA 145.41, QED 0.38
Compound (SMILES): CC[C@@H](C)[C@@H](N)C(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: STGQGYIZOGKZHX-DRMXPCRNSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 499.62, ALogP 4.4, HBA 8, HBD 2, PSA 125.18, QED 0.39
Compound (SMILES): CC(C)C[C@@H](N)C(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: QLYJNZOOGSPPSH-NFBKMPQASA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Detection of In Vitro Inhibition Activity (Enzymatic Activity): In the experiments of in vitro enzymatic activity, the IC50 values of Compound 33, Compound 30, Compound 14, Compound 20, Compound 22, Compound 23, Compound 25, Compound 26, Compound 27, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 2, Compound 3, Compound 4, Compound 76, Compound 77, Compound 78, Compound 48, Compound 47, Compound 45, Compound 44, Compound 43 and AC220 on protein kinase FLT3, FLT3/ITD and BTK were determined. The intracellular segment regions of protein kinase FLT3, FLT3/ITD and BTK were cloned into the insect expression vector pAcG2T, and the proteins were expressed by using an insect expression system, BaculoGold Baculovirus Expression System (BD Pharmingen), with GST tag. The established vectors were transfected into SF9 packaging viruses, so as to infect the SF9-expressed proteins with the viruses.9 μL (6 ng/μL) of purified FLT3 and BTK protein kinase were reacted with 1 μL of three-fold gradient dilution of the above compounds (final concentrations of the agents were 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM, 0.003 μM), respectively, at room temperature for 4 hours;2 μL of ATP and 3 μL of substrate, Poly(4:1 Glu, Tyr)Peptide (Promega, US), were added (final concentrations are 10 μM and 0.2 μg/μL, respectively), and reacted at 37° C. for 1 hour;5 μL of reacted kinase solution was added into 5 μL of ADP-Glo (Promega, US) and reacted at room temperature for 40 min, the kinase reaction was stopped and the remained ATP was consumed;10 μL of kinase detection reagent was added to transfer ADP into ATP, and the newly obtained ATP was detected by using coupled luciferase/fluorescein reaction, then the IC50 values were calculated by using a plotting method based on the Envision reading (Table 3).The experimental results were shown in FIG. 2: the exemplary compounds of the present invention have a strong inhibitory effect on FLT3, FLT3/ITD and BTK protein kinase, and these results demonstrate that the Compound of the present invention is an inhibitor of FLT3 kinase and also inhibits FLT3/ITD and BTK kinase.
Measurement: IC50 = 688 nM (pChEMBL 6.159999847412109)
Descriptors: MW 499.62, ALogP 4.4, HBA 8, HBD 2, PSA 125.18, QED 0.39
Compound (SMILES): CN1CCN(C)C(c2ccc(Nc3nc(-c4cccc(NC(=O)c5cc6c(s5)CCCC6)c4)cn(C)c3=O)cc2)C1=O
InChIKey: RAYABIUAYLVIIX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 582.73, ALogP 4.83, HBA 8, HBD 2, PSA 99.57, QED 0.34
Compound (SMILES): CN1CCN(C)C(c2ccc(Nc3nc(-c4cccc(NC(=O)c5cc6c(s5)CCCC6)c4F)cn(C)c3=O)cc2)C1=O
InChIKey: CWJGFAKENKXHPE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 600.72, ALogP 4.97, HBA 8, HBD 2, PSA 99.57, QED 0.32
Compound (SMILES): CN1CCN(C)C(c2ccc(Nc3nc(-c4cccc(NC(=O)c5cc6c(s5)CCCC6)c4Cl)cn(C)c3=O)cc2)C1=O
InChIKey: NTIUJPKOSDQHQP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 617.18, ALogP 5.48, HBA 8, HBD 2, PSA 99.57, QED 0.3
Compound (SMILES): CN1CCN(C)C(c2ccc(Nc3nc(-c4ccc(C#N)c(NC(=O)c5cc6c(s5)CCCC6)c4)cn(C)c3=O)cc2)C1=O
InChIKey: ZXRQSUPNXDUIPA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 607.74, ALogP 4.7, HBA 9, HBD 2, PSA 123.36, QED 0.33
Compound (SMILES): CN1CCN(C)C(c2ccc(Nc3nc(-c4ccc(Cl)c(NC(=O)c5cc6c(s5)CCCC6)c4)cn(C)c3=O)cc2)C1=O
InChIKey: WIWSXPUJWQMNFO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 617.18, ALogP 5.48, HBA 8, HBD 2, PSA 99.57, QED 0.3
Compound (SMILES): CN1CCN(C)C(c2ccc(Nc3nc(-c4ccc(F)c(NC(=O)c5cc6c(s5)CCCC6)c4)cn(C)c3=O)cc2)C1=O
InChIKey: ZGWZMIIQVITDKD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 600.72, ALogP 4.97, HBA 8, HBD 2, PSA 99.57, QED 0.32
Compound (SMILES): Cc1c(-c2cn(C)c(=O)c(Nc3ccc(C4C(=O)N(C)CCN4C)cc3)n2)ccc(Cl)c1NC(=O)c1cc2c(s1)CCCC2
InChIKey: CMFMSYJMERDRPZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by Lanthascreen assay
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 631.2, ALogP 5.79, HBA 8, HBD 2, PSA 99.57, QED 0.28
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NC(C)c3ccccc3)cc12
InChIKey: FQUHBSCFHGGWQF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 35840 nM (pChEMBL 4.449999809265137)
Descriptors: MW 374.4, ALogP 3.82, HBA 5, HBD 2, PSA 96.3, QED 0.42
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NC(c3ccccc3)c3ccccc3)cc12
InChIKey: DMIJFZDAGCOVSU-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 436.47, ALogP 4.85, HBA 5, HBD 2, PSA 96.3, QED 0.31
Compound (SMILES): COc1ccc(C(C)NC(=O)c2cc3c(ccc4c(C)cc(=O)oc43)oc2=N)cc1
InChIKey: CEBRFHRDNVFBOY-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 404.42, ALogP 3.83, HBA 6, HBD 2, PSA 105.53, QED 0.4
Compound (SMILES): COc1ccc(CNC(=O)c2cc3c(ccc4c(C)cc(=O)oc43)oc2=N)c(OC)c1
InChIKey: ZJRBVJALNVWYRQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 420.42, ALogP 3.27, HBA 7, HBD 2, PSA 114.76, QED 0.38
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NCc3ccccc3Br)cc12
InChIKey: RDRHSWAZLFORIL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 439.26, ALogP 4.02, HBA 5, HBD 2, PSA 96.3, QED 0.37
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NCc3cccc(Br)c3)cc12
InChIKey: NNLAJSUPDKVLFC-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 439.26, ALogP 4.02, HBA 5, HBD 2, PSA 96.3, QED 0.37
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NCc3ccccc3Cl)cc12
InChIKey: WHHWSDAZRVRYPB-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 394.81, ALogP 3.91, HBA 5, HBD 2, PSA 96.3, QED 0.41
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NCc3cccc(Cl)c3)cc12
InChIKey: BNIZIDOQRRXXPZ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 394.81, ALogP 3.91, HBA 5, HBD 2, PSA 96.3, QED 0.41
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)NCc3ccc(C(C)(C)C)cc3)cc12
InChIKey: UMTKCFJRDJJORY-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 57930 nM (pChEMBL 4.239999771118164)
Descriptors: MW 416.48, ALogP 4.55, HBA 5, HBD 2, PSA 96.3, QED 0.38
Compound (SMILES): COc1ccccc1OCCNC(=O)c1cc2c(ccc3c(C)cc(=O)oc32)oc1=N
InChIKey: JBAJEOIIKJZOMX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 24800 nM (pChEMBL 4.610000133514404)
Descriptors: MW 420.42, ALogP 3.14, HBA 7, HBD 2, PSA 114.76, QED 0.28
Compound (SMILES): Cc1cc(=O)oc2c1ccc1oc(=N)c(C(=O)Nc3ccccc3[N+](=O)[O-])cc12
InChIKey: ONWGINPDIZHZJU-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse serum butyrylcholinesterase using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 391.34, ALogP 3.49, HBA 7, HBD 2, PSA 139.44, QED 0.24
Compound (SMILES): CC(C)(C)OC(=O)N1C[C@H](Nc2nc3cc(F)ccc3[nH]2)[C@@H](OC(=O)c2ccc(-c3ccccc3)cc2)C1
InChIKey: ONXOLONSBJTOEF-DQEYMECFSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) by FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 516.57, ALogP 5.63, HBA 6, HBD 2, PSA 96.55, QED 0.33
Compound (SMILES): COc1ccc(N2CCN([C@@H]3CN(C(=O)Nc4cc(Cl)cc(Cl)c4)CC[C@H]3OC(=O)c3ccc(Oc4ccccc4)cc3)CC2)cc1
InChIKey: XFFFVEQRHIOEAE-KKLWWLSJSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin)
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 675.61, ALogP 7.45, HBA 7, HBD 1, PSA 83.58, QED 0.19
Compound (SMILES): Cc1ccc2[nH]c(N[C@H]3CN(C(=O)OC(C)(C)C)C[C@@H]3OC(=O)c3ccc(-c4ccccc4)cc3)nc2c1
InChIKey: KWLJBBUJPGJTAB-UIOOFZCWSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) by FRET assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 512.61, ALogP 5.8, HBA 6, HBD 2, PSA 96.55, QED 0.33
Compound (SMILES): COc1ccc2[nH]c(N[C@H]3CN(C(=O)OC(C)(C)C)C[C@@H]3OC(=O)c3ccc(-c4ccccc4)cc3)nc2c1
InChIKey: QISXYXTUQWAAJT-UIOOFZCWSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) by FRET assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 528.61, ALogP 5.5, HBA 7, HBD 2, PSA 105.78, QED 0.32