lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1Cc2cc(C(N)=O)cnc2N1
InChIKey: HLBSXLCCTVSVBK-RXMQYKEDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 177.21, ALogP 0.54, HBA 3, HBD 2, PSA 68.01, QED 0.66
Compound (SMILES): O=C1c2ccccc2C(=O)c2c1cc(O)c(CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)c2O
InChIKey: ZPYJBMSCFWZBRZ-PTKNJCLRSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Mixed type inhibition of N-terminal His-tagged recombinant human PTP1B expressed in Escherichia coli using pNPP as substrate assessed as inhibition constant preincubated for 15 mins followed by substrate addition and measured after 15 mins by Dixon plot analysis
Measurement: Ki = 3020 nM (pChEMBL 5.519999980926514)
Descriptors: MW 432.38, ALogP -0.81, HBA 10, HBD 6, PSA 173.98, QED 0.31
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc3nc(N4CCCC4)ccc3c2)[nH]1
InChIKey: BPGNCVTVTQPXKS-PXJZQJOASA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 570.78, ALogP 6.04, HBA 6, HBD 2, PSA 94.22, QED 0.26
Compound (SMILES): COCCNc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N
InChIKey: FNGUXMMZSCMHDU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 556.42, ALogP 2.52, HBA 10, HBD 2, PSA 134.4, QED 0.29
Compound (SMILES): COc1cc2c(cc1OC)[C@@H](C)C(=O)N(C)C=C2
InChIKey: DIOZLEANHAFFJH-SECBINFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 247.29, ALogP 2.25, HBA 3, HBD 0, PSA 38.77, QED 0.8
Compound (SMILES): Nc1nc(Cl)cc(-c2nn(C(F)F)cc2Cc2ccccc2OCC(=O)N2CCOCC2)n1
InChIKey: YIIRCSQUJPUWPZ-UHFFFAOYSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: Binding affinity to human recombinant His-tagged ADCY10 assessed as dissociation constant and measured for 600 sec by SPR analysis
Measurement: Kd = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 478.89, ALogP 2.8, HBA 8, HBD 1, PSA 108.39, QED 0.52
Compound (SMILES): CCC(=O)Nc1cccc(-c2c(-c3ccc(N4CCN(C)CC4)cc3)[nH]c3ncnc(OC(C)C)c23)c1
InChIKey: WLQUQTHWWMACGB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human GST-tagged EGFR L858R/T790M/C797S mutant expressed in Sf9 cells assessed as substrate phosphorylation using TK-peptide as substrate incubated for 10 mins by HTRF assay
Measurement: IC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 498.63, ALogP 5.18, HBA 6, HBD 2, PSA 86.38, QED 0.37
Compound (SMILES): Nc1nc(Cl)cc(-c2nn(C(F)F)cc2Cc2ccccc2OCCN2CCOC[C@@H]2CO)n1
InChIKey: XVGSKZXXLKUEIO-INIZCTEOSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: Binding affinity to human recombinant His-tagged ADCY10 assessed as dissociation constant and measured for 600 sec by SPR analysis
Measurement: Kd = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 494.93, ALogP 2.63, HBA 9, HBD 2, PSA 111.55, QED 0.44
Compound (SMILES): COC(=O)[C@H]1COCCN1CCOc1ccccc1Cc1cn(C(F)F)nc1-c1cc(Cl)nc(N)n1
InChIKey: XHTFJTUBYAPEAW-QGZVFWFLSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: Binding affinity to human recombinant His-tagged ADCY10 assessed as dissociation constant and measured for 600 sec by SPR analysis
Measurement: Kd = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 522.94, ALogP 2.81, HBA 10, HBD 1, PSA 117.62, QED 0.33
Compound (SMILES): COc1cccc(N2CCN(Cc3nc(N)nc(Nc4ccc(C)c(C)c4)n3)CC2)c1
InChIKey: STKSULQULJWEMU-UHFFFAOYSA-N
Target: NADPH oxidase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBY0
Assay: Inhibition of human NOX3
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 419.53, ALogP 3.15, HBA 8, HBD 2, PSA 92.43, QED 0.63
Compound (SMILES): NC(=O)c1cc2c(N)ncnc2cc1-c1ccc2cc[nH]c2c1
InChIKey: FBHHPRBEZWKUQB-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Inhibition of PI4KB catalytic domain (unknown origin) assessed as enzyme residual activity incubated for 60 mins using ATP as substrate by ATP-Glo luminescent assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 303.32, ALogP 2.46, HBA 4, HBD 3, PSA 110.68, QED 0.53
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2cc(O)ccc12
InChIKey: BDFWQTZENXBWRT-UHFFFAOYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 473.89, ALogP 1.94, HBA 6, HBD 3, PSA 130.55, QED 0.46
Compound (SMILES): COc1cc(/C=C/C(=O)OCCCCCCN(CCCOC(=O)c2cc(OC)c(OC)c(OC)c2)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: DSNGJQWYZOVSFA-GHRIWEEISA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 50.2 nM (pChEMBL 7.300000190734863)
Descriptors: MW 791.89, ALogP 6.98, HBA 14, HBD 0, PSA 150.66, QED 0.03
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3cccnc3nc2OC)o1
InChIKey: SPRMKKWNBGDRLB-RPBOFIJWSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 < 1.5 nM (pChEMBL 8.824000358581543)
Descriptors: MW 547.7, ALogP 5.5, HBA 8, HBD 1, PSA 110.45, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc3nc(-n4cccn4)ccc3c2)[nH]1
InChIKey: LGSKPPYSKWOZRH-IAPPQJPRSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 567.74, ALogP 5.63, HBA 7, HBD 2, PSA 108.8, QED 0.21
Compound (SMILES): COc1ccc(C(F)(F)F)cc1NC(=O)CN1CCN(S(=O)(=O)N2CCC(C)CC2)CC1
InChIKey: ZJYQICVSMCOILE-UHFFFAOYSA-N
Target: Calcium-activated potassium channel subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12791
Assay: Inhibition of Maxi-K (unknown origin) expressed in HEK293 cells measured by thallium flux assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 478.54, ALogP 2.25, HBA 5, HBD 1, PSA 82.19, QED 0.68
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: IFWBAIGKQKRJGJ-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 552.58, ALogP 5.53, HBA 6, HBD 3, PSA 111.85, QED 0.24
Compound (SMILES): C[C@H]1C(=O)N(C)C=Cc2cc(CC3CCOCC3)ccc21
InChIKey: ZXWPECAQBZLMMU-CYBMUJFWSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 285.39, ALogP 3.2, HBA 2, HBD 0, PSA 29.54, QED 0.83
Compound (SMILES): C[C@@H](Oc1cc(NC(=O)c2cn(CCc3cnn(C)c3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: ZZKZJASJVNSLSZ-OAHLLOKOSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 668.34, ALogP 5.95, HBA 10, HBD 1, PSA 140.61, QED 0.19
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(N)=O)C(C)C)C(C)C)C(C)C)[C@@H](C)O
InChIKey: XQYWLRVRAMKFHZ-WYBJURANSA-N
Target: Vasoactive intestinal polypeptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41587
Assay: Agonist activity at VPAC2 in human SH-SY5Y cells assessed as cAMP accumulation incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay
Measurement: EC50 = 0.06 nM (pChEMBL 10.220000267028809)
Descriptors: MW 4662.51
Compound (SMILES): COc1cc(C(=O)OCCCN(CCCCCOC(=O)c2c3ccccc3cc3ccccc23)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: MMPHBAKNXPIONF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 93.7 nM (pChEMBL 7.03000020980835)
Descriptors: MW 761.87, ALogP 8.47, HBA 11, HBD 0, PSA 122.97, QED 0.03
Compound (SMILES): O=C1NC(=S)NC(=O)C1=Cc1cc(-c2cc(Cl)c(O)c(Cl)c2)ccc1OCc1ccc(Cl)cc1
InChIKey: QVBNRWITESBSFO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of recombinant human PTP1B using pNPP as substrate preincubated for 5 mins followed by substrate addition assessed as reduction in p-nitrophenol release
Measurement: IC50 = 5160 nM (pChEMBL 5.289999961853027)
Descriptors: MW 533.82, ALogP 5.51, HBA 5, HBD 3, PSA 87.66, QED 0.23
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2cc(CO)ccc12
InChIKey: UYOQIJAROUNQLT-UHFFFAOYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 487.92, ALogP 1.73, HBA 6, HBD 3, PSA 130.55, QED 0.42
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(C2=CC3SC=NC3C=C2)[nH]1
InChIKey: DAYIQZXDBBYZNJ-HNMULJTMSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 509.72, ALogP 4.69, HBA 6, HBD 2, PSA 90.45, QED 0.42
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc4nc(C(C)=O)c(=O)n(C5CCCC5)c4n3)cc2)CC1
InChIKey: JWXFZMDNUUBYBZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E1 (unknown origin)
Measurement: IC50 = 7944 nM (pChEMBL 5.099999904632568)
Descriptors: MW 461.57, ALogP 3.39, HBA 9, HBD 1, PSA 96.25, QED 0.56
Compound (SMILES): NC1CCCC(NS(=O)(=O)c2ccc(-c3ccc(CSc4nc5c(c(=O)[nH]4)CCC5)cc3)cc2)C1
InChIKey: MDTVXTHPTRFSHT-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of MMP-8 (unknown origin) using fTHP-15(FAM) as substrate
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 510.69, ALogP 3.77, HBA 6, HBD 3, PSA 117.94, QED 0.33
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccccc3[nH]c2=O)[nH]1
InChIKey: SVRMBDNTAIBTAK-NOZRDPDXSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 < 1.5 nM (pChEMBL 8.824000358581543)
Descriptors: MW 517.67, ALogP 4.74, HBA 5, HBD 3, PSA 110.95, QED 0.32
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccc(C(N)=O)cc3)ccc2F)c1
InChIKey: HZQICPCUMLWHPZ-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 594.61, ALogP 5.23, HBA 6, HBD 4, PSA 142.05, QED 0.19
Compound (SMILES): COCCNc1cc(NC(=O)c2cn(CC3CC3)c3ccc(C=O)nc23)ncc1C#N
InChIKey: MLYCCHBSSYFWCH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.46, ALogP 2.84, HBA 8, HBD 2, PSA 121.93, QED 0.4
Compound (SMILES): CC(C)Oc1cc(NC(=O)c2cn(C)c3ccc(C=O)nc23)ncc1C#N
InChIKey: ZKXNHRMKLNQUEM-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 363.38, ALogP 2.69, HBA 7, HBD 1, PSA 109.9, QED 0.7
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@H]2C[C@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCNC(=O)CCc2cccc(-c3ccc4nc(-c5cccnc5N)n(-c5ccc(C6(N)CCC6)cc5)c4n3)c2)C(C)(C)C)cc1
InChIKey: XYGBNRINQSQNJG-FMXPWWRVSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of AKT3 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 120 mins by hotspot kinase assay
Measurement: IC50 = 407 nM (pChEMBL 6.389999866485596)
Descriptors: MW 1114.47
Compound (SMILES): Cn1ccc2cc(-c3cnc4ccc(C(=O)N5CCCCC5)cc4n3)ccc2c1=O
InChIKey: URHPFANOQLIROT-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of acetylcholinesterase (unknown origin)
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 398.47, ALogP 3.77, HBA 5, HBD 0, PSA 68.09, QED 0.52
Compound (SMILES): CN1CCC(N(C)C(=O)Nc2ccc3c(c2)c(C(N)=O)nn3CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)CC1
InChIKey: HOERATAUJMEIFL-UHFFFAOYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 627.12, ALogP 2.79, HBA 7, HBD 3, PSA 145.9, QED 0.32
Compound (SMILES): N#Cc1cccc(C(N)(CCC2CC2)c2ccc(F)c(NC(=O)c3cc(C(F)(F)F)nn3-c3cccc(CN)c3)c2)n1
InChIKey: UYAYDZPBNCJYMZ-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of endogenous human plasma kallikrein using Z-Phe-Arg-AMC.HCl as substrate measured after 5 mins by microplate reader analysis
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 577.59, ALogP 5.4, HBA 7, HBD 3, PSA 135.64, QED 0.23
Compound (SMILES): CC1C(=O)N(C)C=Cc2cc(OCC(C)(C)O)ccc21
InChIKey: HXRUMFNZRLZZAE-UHFFFAOYSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 275.35, ALogP 2.38, HBA 3, HBD 1, PSA 49.77, QED 0.92
Compound (SMILES): CC(=O)N1CCN(c2cnc3ccc(-c4cnc(Cl)c(NS(=O)(=O)c5ccc(F)cc5)c4)cc3n2)CC1
InChIKey: KGNNMSGRBVKSQP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) by TR-FRET assay
Measurement: IC50 = 5.36 nM (pChEMBL 8.270000457763672)
Descriptors: MW 541.01, ALogP 3.95, HBA 7, HBD 1, PSA 108.39, QED 0.38
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@H]2C[C@H](OCc3ccccc3)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCNC(=O)CCc2cccc(-c3ccc4nc(-c5cccnc5N)n(-c5ccc(C6(N)CCC6)cc5)c4n3)c2)C(C)(C)C)cc1
InChIKey: VPXQUOXZEXEWAH-WAPOASIOSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of AKT3 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 120 mins by hotspot kinase assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 1204.6
Compound (SMILES): COc1cccc2cc(-c3nn(C4CCOCC4)c4ncnc(N)c34)[nH]c12
InChIKey: ZEKMMWTXUQTYFE-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of human PI3Kbeta preincubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 364.41, ALogP 2.92, HBA 7, HBD 2, PSA 103.87, QED 0.58
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccc(C)nc3cc2OC)[nH]1
InChIKey: BBRYNDYUWCVFAV-SXOMAYOGSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 < 0.3 nM (pChEMBL 9.52299976348877)
Descriptors: MW 559.76, ALogP 6.15, HBA 6, HBD 2, PSA 100.21, QED 0.24
Compound (SMILES): O=C(NO)c1ccc(Cn2c([C@@H]3CC4(CC4)CN3c3ncnc4[nH]cnc34)nc3cccc(F)c3c2=O)cc1
InChIKey: DYAWZNJZRKNKAO-IBGZPJMESA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) measured by fluorescence based assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 526.53, ALogP 3.1, HBA 9, HBD 3, PSA 141.92, QED 0.23
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cccc(C(NCC3CC3)c3ccccc3)c2)c1
InChIKey: QZQLNMURVWFZTC-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader.
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 519.57, ALogP 5.69, HBA 5, HBD 3, PSA 84.97, QED 0.27
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc(CNC(=O)CC(=O)NO)cc4)ncc3F)cc2n1C(C)C
InChIKey: LFWRZTGKNXDMJU-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 509.52, ALogP 3.92, HBA 8, HBD 4, PSA 134.06, QED 0.16
Compound (SMILES): CC1(Cn2nc(-c3ccc4oc(N)nc4c3)c3c(N)nc(N)nc32)CSC1
InChIKey: YTOAJUIMCNAYNE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to mTOR (unknown origin) assessed as inhibition constant measured after 1 hr by TR-FRET assay
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 382.45, ALogP 2.13, HBA 10, HBD 3, PSA 147.69, QED 0.48
Compound (SMILES): COc1cc(C(=O)OCCCCCCN(CCCOC(=O)c2c3ccccc3cc3ccccc23)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: FWGMXQLBHUZENX-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 54.1 nM (pChEMBL 7.269999980926514)
Descriptors: MW 775.9, ALogP 8.86, HBA 11, HBD 0, PSA 122.97, QED 0.03
Compound (SMILES): CN1CCN(c2ccc(CN(CC(C)(C)C)c3nccc(C#N)n3)cc2)CC1
InChIKey: CROHKCAOPCLRAC-UHFFFAOYSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of Cathepsin B (unknown origin) assessed as inhibition of AFC release using sequence RR labelled with AFC as substrate by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 378.52, ALogP 3.15, HBA 6, HBD 0, PSA 59.29, QED 0.8
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccc(=O)n(C)c3cc2OC)[nH]1
InChIKey: LPSGBWOQABTCDV-FTJBHMTQSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 < 0.3 nM (pChEMBL 9.52299976348877)
Descriptors: MW 575.75, ALogP 5.15, HBA 7, HBD 2, PSA 109.32, QED 0.27
Compound (SMILES): CC(C)n1nc(-c2cc3cccc(O)c3[nH]2)c2c(N)ncnc21
InChIKey: DWMSSWRQJCJQFL-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 308.35, ALogP 2.84, HBA 6, HBD 3, PSA 105.64, QED 0.53
Compound (SMILES): C[C@H]1C(=O)N(C)C=Cc2cc(CN3CCCC3)ccc21
InChIKey: UBWXHPCCGJFRKO-CYBMUJFWSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 270.38, ALogP 2.83, HBA 2, HBD 0, PSA 23.55, QED 0.82
Compound (SMILES): NC(=O)c1cc2c(N)ncnc2cc1-c1ccc2c(c1)OCO2
InChIKey: BOVRDQZOWROYFT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Inhibition of PI4KB catalytic domain (unknown origin) assessed as enzyme residual activity incubated for 60 mins using ATP as substrate by ATP-Glo luminescent assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 308.3, ALogP 1.71, HBA 6, HBD 2, PSA 113.35, QED 0.74
Compound (SMILES): CCN(C)C(=O)Oc1ccc(CNc2nc3c(cnn3C3CCCC3)c(=O)[nH]2)cc1OC
InChIKey: NEWFCVAVIWJNER-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine BChE
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 440.5, ALogP 3.31, HBA 8, HBD 2, PSA 114.37, QED 0.58
Compound (SMILES): COc1cc(/C=C/C(=O)OCCCN(CCCCCCCOC(=O)c2c3ccccc3cc3ccccc23)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: ISYZGTRQOHXEJA-FCDQGJHFSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 71.1 nM (pChEMBL 7.150000095367432)
Descriptors: MW 815.96, ALogP 9.65, HBA 11, HBD 0, PSA 122.97, QED 0.02
Compound (SMILES): CC[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(F)c2c(=O)n1CCCCCC(=O)NO
InChIKey: WMOGXHBOPOTASI-AWEZNQCLSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) measured by fluorescence based assay
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 468.49, ALogP 2.83, HBA 9, HBD 4, PSA 150.71, QED 0.16
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cccc(C(CCC3CC3)c3ccccc3)c2)c1
InChIKey: LVGPKQXQIQRVCT-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 518.58, ALogP 6.92, HBA 4, HBD 2, PSA 72.94, QED 0.25
Compound (SMILES): C[C@H](Oc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: CGZXQBNAWSMHFF-INIZCTEOSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 673.36, ALogP 5.3, HBA 10, HBD 1, PSA 135.26, QED 0.23
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(C2=CC3OC=NC3C=C2)[nH]1
InChIKey: PTTHXWHSGFRYLP-HNMULJTMSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 493.65, ALogP 3.98, HBA 6, HBD 2, PSA 99.68, QED 0.45
Compound (SMILES): CCOc1ccc2c(c1)C(c1c[nH]cn1)=CN(C)C(=O)[C@@H]2C
InChIKey: BLPQMWXVHZTOMY-LLVKDONJSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 297.36, ALogP 2.77, HBA 3, HBD 1, PSA 58.22, QED 0.95
Compound (SMILES): CCC1(C)CN(c2ccc3oc(N)nc3c2)c2c(N)ncnc21
InChIKey: CEPOCJCCKQHPAE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to mTOR (unknown origin) assessed as inhibition constant measured after 1 hr by TR-FRET assay
Measurement: Ki = 34.6 nM (pChEMBL 7.460000038146973)
Descriptors: MW 310.36, ALogP 2.6, HBA 7, HBD 2, PSA 107.09, QED 0.75
Compound (SMILES): COc1ccc(Cl)cc1NC(=O)CN1CCN(S(=O)(=O)N2CCC(C)CC2)C[C@H]1C
InChIKey: FRYJNJTUMJQBEB-MRXNPFEDSA-N
Target: Calcium-activated potassium channel subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12791
Assay: Inhibition of Maxi-K (unknown origin) expressed in HEK293 cells measured by thallium flux assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 459.01, ALogP 2.27, HBA 5, HBD 1, PSA 82.19, QED 0.71
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)nc3c2C[C@@H]2COCCN32)cn1
InChIKey: KDKHUZABTIJMDY-GFCCVEGCSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC1 (unknown origin)
Measurement: IC50 = 574 nM (pChEMBL 6.239999771118164)
Descriptors: MW 355.4, ALogP 0.11, HBA 9, HBD 1, PSA 102.52, QED 0.8
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3cn(C)nc3cc2OC)[nH]1
InChIKey: LVBJLNXVNGDXNM-RPBOFIJWSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 548.73, ALogP 5.18, HBA 7, HBD 2, PSA 105.14, QED 0.29
Compound (SMILES): CCS(=O)(=O)c1ccc2c(c1)C(c1ccncc1)=CN(C)C(=O)C2C
InChIKey: YQEZEDBEWDLLMS-UHFFFAOYSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 356.45, ALogP 2.84, HBA 4, HBD 0, PSA 67.34, QED 0.85
Compound (SMILES): C[C@H]1C(=O)N(C)C=Cc2ccccc21
InChIKey: YSRQSFSJQWPTEK-SECBINFHSA-N
Target: C-C motif chemokine 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P13500
Assay: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 187.24, ALogP 2.23, HBA 1, HBD 0, PSA 20.31, QED 0.61
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCNC(=O)CCc2cccc(-c3ccc4nc(-c5cccnc5N)n(-c5ccc(C6(N)CCC6)cc5)c4n3)c2)C(C)(C)C)cc1
InChIKey: XYGBNRINQSQNJG-IQDHSYJRSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of AKT3 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 120 mins by hotspot kinase assay
Measurement: IC50 = 544 nM (pChEMBL 6.260000228881836)
Descriptors: MW 1114.47
Compound (SMILES): Cc1n[nH]c(C)c1Cc1sc2c(c1C(=O)N1C[C@@H](O)CO1)c(=O)n(C)c(=O)n2CC(C)C
InChIKey: ISIVOJWVBJIOFM-CYBMUJFWSA-N
Target: Monocarboxylate transporter 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63344
Assay: Binding affinity to MCT2 in rat Erythrocyte assessed as inhibition constant
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 461.54, ALogP 1.1, HBA 9, HBD 2, PSA 122.45, QED 0.59
Compound (SMILES): OCc1cn(Cc2ccc(-c3noc(-c4ccc(OCCF)c(C(F)(F)F)c4)n3)cc2)nn1
InChIKey: DCPOKPSFSZPLMQ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: In Vitro Binding Assay: Newly synthesized compounds were first evaluated for binding potency toward S1P1 by a [32P]S1P competitive binding assay following published procedure (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9), and using S1P as a reference compound. [32P]S1P was first prepared by incubating sphingosine and [γ-32P]ATP with sphingosine kinase 1 as previously reported (J. Rosenberg, H. Liu, Z. Tu, A practical process for the preparation of [32P]S1P and binding assay for S1P receptor ligands, Appl. Radiat. Isot. 102 (2015) 5-9). [32P]S1P was dissolved in DMSO, and then diluted in the assay buffer (50 mM HEPES-Na with 5 mM MgCl2, 1 mM CaCl2, and 0.5% fatty acid-free bovine serum albumin, pH=7.5). Compounds were dissolved in DMSO and diluted to different concentrations with assay buffer, followed by adding commercial cell membranes expressing recombinant human S1P receptors (1, 2, 3, 4, and 5) in the assay buffer at room temperature in 96-well plate. [32P]S1P solution was then added to give a final volume of 150 μL containing 0.1 nM of [32P]S1P and 1 μg of membrane protein per well. Competitive binding was performed for 60 min at room temperature and terminated by collecting the membranes onto 96-well glass fiber (GF/B) filtration plates (Millipore, Billerica, Mass.). Each filter was washed with 200 μL of assay buffer for five times. The filter bound radionuclide was measured by a Beckman LS3801 scintillation counter using Cherenkov counting. The reported IC50 values were calculated using the 4 parameter equation, least-square non-linear regression curve-fit, with GraphPad Prism software (GraphPad Software, Inc). Each assay was repeated at least three times with duplicate wells for each compound; the reported values (mean±SD, nM) are calculated from the average of all assays. Assays for compounds which showed no activity (IC50>1000 nM) were only repeated twice.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 463.39, ALogP 3.9, HBA 8, HBD 1, PSA 99.09, QED 0.4
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccc(C)nc3cc2OC)[nH]1
InChIKey: ATMXJCYXICJPMG-FTJBHMTQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 545.73, ALogP 5.76, HBA 6, HBD 2, PSA 100.21, QED 0.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc(-c3cnccn3)cc2)[nH]1
InChIKey: DDCDBKDXBVPBNH-FTJBHMTQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 528.7, ALogP 5.35, HBA 6, HBD 2, PSA 103.87, QED 0.31
Compound (SMILES): C[C@@H](Oc1cc(NC(=O)c2cn(CCN3CCC(N4CCOCC4)CC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: FICZVIYFMGFZHX-HXUWFJFHSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 756.49, ALogP 5.77, HBA 11, HBD 1, PSA 138.5, QED 0.2
Compound (SMILES): Cc1ccccc1Oc1cc(-n2c(=O)cc(C(F)(F)c3ccccc3)[nH]c2=O)c2ccccc2c1Cl
InChIKey: ORZQWCVWJWOYDJ-UHFFFAOYSA-N
Target: Branched-chain-amino-acid aminotransferase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O15382
Assay: Inhibition of human recombinant BCAT2 using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 504.92, ALogP 6.57, HBA 4, HBD 1, PSA 64.09, QED 0.29
Compound (SMILES): CNC(=O)Oc1cccc2c1CCC1C2CCN1CCC1CCCCC1
InChIKey: HUGQDDJXYKRDAL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Binding affinity to Muscarinic acetylcholine receptor M3 (unknown origin) assessed as inhibition constant
Measurement: Ki = 1515 nM (pChEMBL 5.820000171661377)
Descriptors: MW 356.51, ALogP 4.48, HBA 3, HBD 1, PSA 41.57, QED 0.86
Compound (SMILES): CC(Oc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)ccc(F)c1Cl
InChIKey: GEPOJFLYFUAKKO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 690.36, ALogP 6.05, HBA 9, HBD 1, PSA 122.37, QED 0.17
Compound (SMILES): Cc1c(Cl)c(=O)oc2cc(OCCCCSC(=S)N3C(C)CCCC3C)ccc12
InChIKey: IKYVMKQIWKXWDL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using p-tyramine as substrate incubated for 15 mins followed by substrate addition and measured upto 20 mins by Amplex Red assay
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 454.06, ALogP 6.19, HBA 5, HBD 0, PSA 42.68, QED 0.29
Compound (SMILES): CC[C@H](CC(=O)c1cc2cc(OC)c(OC)cc2[se]1)C(=O)O
InChIKey: BWQHPFYQJHFPHN-SECBINFHSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Mus musculus
UniProt: Q3TBT3
Assay: Agonist activity at STING in mouse RAW264.7 cells harboring IRF-inducible luciferase reporter construct assessed as increase in relative fluorescence unit incubated for 12 hrs by Quanti-luc reagent based assay
Measurement: EC50 = 5710 nM (pChEMBL 5.239999771118164)
Descriptors: MW 369.28
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccncc3nc2OC)o1
InChIKey: ZRFLMIZPTHEEJS-RPBOFIJWSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 547.7, ALogP 5.5, HBA 8, HBD 1, PSA 110.45, QED 0.28
Compound (SMILES): O=C(O)CNC(=O)c1nc(-c2ccccc2-c2ccccc2)ccc1O
InChIKey: CWMDDHZCTORRMW-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of recombinant N-terminal hexahistidine-tagged human PDH2 (181 to 426 residues) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by substrate addition and measured after 15 mins using CODD peptide DLDLEMLAPYIPMDDDFQL as substrate by SPE-MS-based assay
Measurement: IC50 = 11500 nM (pChEMBL 4.940000057220459)
Descriptors: MW 348.36, ALogP 2.94, HBA 4, HBD 3, PSA 99.52, QED 0.66
Compound (SMILES): COCCNc1ccnc(NC(=O)c2cn(C)c3ccc(C=O)nc23)c1
InChIKey: ANADUTKZNGPTEL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 353.38, ALogP 2.09, HBA 7, HBD 2, PSA 98.14, QED 0.5
Compound (SMILES): Cc1cc(C(N)(CCC2CC2)c2ccc(F)c(NC(=O)c3cc(C(F)(F)F)nn3-c3cccc(CN)c3)c2)ccn1
InChIKey: PYONXWOUVYIBRU-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 566.6, ALogP 5.84, HBA 6, HBD 3, PSA 111.85, QED 0.22
Compound (SMILES): Cc1c(Br)cc(NC(=O)CS(=O)(=O)O)cc1Br
InChIKey: PGYFUNHIFMBZCB-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 22 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2R2
Assay: Inhibition of LYP (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.05, ALogP 2.35, HBA 3, HBD 2, PSA 83.47, QED 0.78
Compound (SMILES): Cc1c(Cl)c(=O)oc2cc(OCCCCSC(=S)N3CCCCC3C)ccc12
InChIKey: QPKSHJTZCXULAH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using p-tyramine as substrate incubated for 15 mins followed by substrate addition and measured upto 20 mins by Amplex Red assay
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 440.03, ALogP 5.81, HBA 5, HBD 0, PSA 42.68, QED 0.32
Compound (SMILES): COc1cccc2ccc(-c3cc(-c4ccc5cccc(OC)c5c4O)c4cccc(OC)c4c3O)c(O)c12
InChIKey: QNSPJOAEPRYOBU-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Partial agonist activity at PPARalpha (unknown origin) assessed as increase in PRIP/RAP250 coactivator peptide requirement by Lanthascreen TR-FRET assay
Measurement: EC50 = 58200 nM (pChEMBL 4.239999771118164)
Descriptors: MW 518.57, ALogP 7.62, HBA 6, HBD 3, PSA 88.38, QED 0.22
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccccc3n(C)c2=O)[nH]1
InChIKey: XLXMVDANDBLJOJ-RPBOFIJWSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 531.7, ALogP 4.75, HBA 6, HBD 2, PSA 100.09, QED 0.35
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(O)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: XXMBQXWQIGCREG-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of purified human plasma kallikrein using H-D-Pro-Phe-Arg-pNA.2HCl as substrate measured after 3 mins by microplate reader analysis
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 553.56, ALogP 5.56, HBA 6, HBD 3, PSA 106.06, QED 0.24
Compound (SMILES): C[C@H]1C(=O)N(C)C=C(c2cnn(C)c2)c2cc([C@@H](O)CO)ccc21
InChIKey: CJVJSGBELMMESS-DIFFPNOSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 327.38, ALogP 1.41, HBA 5, HBD 2, PSA 78.59, QED 0.89
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc3nc(OC)ccc3c2)[nH]1
InChIKey: VOCUPJYYWCXUPO-RSXGOPAZSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 531.7, ALogP 5.45, HBA 6, HBD 2, PSA 100.21, QED 0.3
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccccc3)ccc2F)c1
InChIKey: NQFNNZJJOCPZCP-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of purified human plasma kallikrein using H-D-Pro-Phe-Arg-pNA.2HCl as substrate measured after 3 mins by microplate reader analysis
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 551.59, ALogP 6.13, HBA 5, HBD 3, PSA 98.96, QED 0.22
Compound (SMILES): COc1cc(C(=O)OCCCCCCN(CCCOC(=O)c2cc(OC)c(OC)c(OC)c2)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: IOPOLXYULUWSMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 765.85, ALogP 6.58, HBA 14, HBD 0, PSA 150.66, QED 0.04
Compound (SMILES): CC(C)n1nc(-c2cc3cc(O)cc(F)c3[nH]2)c2c(N)ncnc21
InChIKey: LUKIMGGLSGHDAN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 326.34, ALogP 2.98, HBA 6, HBD 3, PSA 105.64, QED 0.52