lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccccc4)n3)cc2C(F)(F)F)CC1
InChIKey: CWFRZEJQFAQELA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PknB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WI81
Assay: Binding affinity to Mycobacterium tuberculosis recombinant N-terminal His-tagged PknB (1 to 331 residues) expressed in Escherichia coli DH5alpha cells by microscale thermophoresis analysis
Measurement: Kd = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 413.45, ALogP 4.66, HBA 5, HBD 1, PSA 44.29, QED 0.67
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)OCC3(C(F)(F)F)CC3)nc2C2(CCCCC2)C1(C)C
InChIKey: JDELMZBOFIXWGA-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 440.47, ALogP 4.71, HBA 5, HBD 1, PSA 84.42, QED 0.74
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1CCN1CCN(Cc2ccccc2)CC1
InChIKey: BNGICRROXYSOFL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis
Measurement: Ki = 1667 nM (pChEMBL 5.78000020980835)
Descriptors: MW 408.57, ALogP 3.06, HBA 5, HBD 0, PSA 39.15, QED 0.76
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-KAYWLYCHSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 613.58, ALogP 3.41, HBA 7, HBD 2, PSA 105.9, QED 0.32
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@H]1CSSC[C@@H](C(N)=O)NC1=O
InChIKey: ADTNZHNGYYAVIN-OGFQRHRDSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production incubated for 30 mins by LANCE cAMP assay
Measurement: EC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 886.08, ALogP -5.11, HBA 13, HBD 15, PSA 413.68, QED 0.02
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(C5C=CCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: LZTPSBCGWGMOMP-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 526.65, ALogP 3.59, HBA 10, HBD 2, PSA 104.34, QED 0.37
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(Cl)c(Br)c(Cl)c4)nn32)CC1
InChIKey: SXKQCOANBPFCHG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 297 nM (pChEMBL 6.53000020980835)
Descriptors: MW 527.25, ALogP 4.5, HBA 5, HBD 2, PSA 93.25, QED 0.45
Compound (SMILES): O=C1CC2CCc3ccsc3C2=NN1Cc1ccc(CN2CCN(Cc3ccccc3)CC2)cc1
InChIKey: FMHFUABJEGMXDA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis
Measurement: Ki = 1261 nM (pChEMBL 5.900000095367432)
Descriptors: MW 484.67, ALogP 4.76, HBA 5, HBD 0, PSA 39.15, QED 0.51
Compound (SMILES): CCCCOc1cc2c(c3c(=O)oc4ccccc4c13)C(=O)C=CC2=O
InChIKey: RLGWROLOWFOSKM-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of CDC25B (unknown origin)
Measurement: IC50 = 46100 nM (pChEMBL 4.340000152587891)
Descriptors: MW 348.35, ALogP 4.06, HBA 5, HBD 0, PSA 73.58, QED 0.4
Compound (SMILES): O=C1NC2([C@@H](O)[C@@H]3C=CCCC3)C(=O)O[C@H]2[C@H]1CCCl
InChIKey: OLSLVDNVMYYZGX-CAMXFFFOSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of beta5 proteasome (unknown origin)
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 299.75, ALogP 0.74, HBA 4, HBD 2, PSA 75.63, QED 0.46
Compound (SMILES): Cc1ccc(-c2ccc3c(C)n[nH]c3c2)c2c1[C@@H](N(C)C(=O)c1ncccc1C(F)F)CCC2
InChIKey: ZGVMLURVURNUQI-QHCPKHFHSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of his-tagged wild type c-MET (1050 to 1346 residues) (unknown origin) by ADP-glo assay
Measurement: IC50 = 4940 nM (pChEMBL 5.309999942779541)
Descriptors: MW 460.53, ALogP 6.33, HBA 3, HBD 1, PSA 61.88, QED 0.39
Compound (SMILES): CCOC(=O)c1nn(-c2ccccc2)cc1CN(C)[C@@H]1CCSC1
InChIKey: CDDSADAPSRSSJF-MRXNPFEDSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-methylspiperone from D4 (unknown origin) receptor expressed in HEK293T cells assessed as inhibition constant
Measurement: Ki = 320 nM (pChEMBL 6.5)
Descriptors: MW 345.47, ALogP 2.99, HBA 6, HBD 0, PSA 47.36, QED 0.75
Compound (SMILES): Cc1noc(-c2ccccc2)c1C#CCCCCCNC(=O)C(C)S
InChIKey: HAKJNBQITNLGKA-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 356.49, ALogP 4, HBA 4, HBD 2, PSA 55.13, QED 0.45
Compound (SMILES): CCCN(CCc1ccc(CCN(CCC)[C@H]2CCc3c(O)cccc3C2)cc1)[C@@H]1CCc2cc(O)c(O)cc2C1
InChIKey: FWACCHRUKMDWQL-ZWXJPIIXSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human D2 receptor expressed in CHO cells assessed as stimulation of [35S]GTPgammaS binding by Perkin elmer analysis
Measurement: EC50 = 5.29 nM (pChEMBL 8.279999732971191)
Descriptors: MW 556.79, ALogP 6.43, HBA 5, HBD 3, PSA 67.17, QED 0.22
Compound (SMILES): CN1CCC(n2cc(Nc3nc(OC4(C)CC4)c4nc(-c5cncnc5)ccc4n3)cn2)CC1
InChIKey: QQIQOMIKWUAMAA-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51617
Assay: Inhibition of IRAK1 (unknown origin) in presence of 25 uM ATP
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 457.54, ALogP 3.62, HBA 10, HBD 1, PSA 106.77, QED 0.46
Compound (SMILES): COc1ccc(S(=O)(=O)N2[C@H](C(=O)NO)C[C@@H]3CCN(C(=O)CCc4ccccc4)C[C@@H]32)cc1
InChIKey: ODKPYAOVENFRFV-NYVOZVTQSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of MMP12 (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 487.58, ALogP 1.81, HBA 6, HBD 2, PSA 116.25, QED 0.45
Compound (SMILES): COc1cccc(C2(O)CCN(C(=O)Cc3cccc([N+](=O)[O-])c3)CC2CN(C)C)c1
InChIKey: USGDSNXARSJEOU-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 1987 nM (pChEMBL 5.699999809265137)
Descriptors: MW 427.5, ALogP 2.44, HBA 6, HBD 1, PSA 96.15, QED 0.54
Compound (SMILES): Fc1ccccc1-c1csc(-c2csc(Nc3cc(Cl)cc(Cl)c3)n2)n1
InChIKey: XODLULCLYUBWDK-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethyl-0-resorufin as substrate incubated for 30 mins in presence of NADPH by EROD assay
Measurement: IC50 = 904.8 nM (pChEMBL 6.039999961853027)
Descriptors: MW 422.34, ALogP 7.12, HBA 5, HBD 1, PSA 37.81, QED 0.38
Compound (SMILES): Cc1cc(Nc2ncc(Cl)c(Nc3ccc4c(c3)B(O)OC4)n2)c(OC(C)C)cc1C1CCNCC1
InChIKey: FHSQKPCVTHNWQA-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK cytoplasmic domain (1058 to 1620 residues) L1196M mutant expressed in baculovirus-infected Sf21 cells using LANCE Ultra ULight-PolyGT substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 507.83
Compound (SMILES): Cc1nc(N2CCCN(C(=O)c3ccco3)CC2)c2c3c(sc2n1)CCCC3
InChIKey: OQXILFAPNLXMTN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 receptor expressed in HEK293 cell membranes assessed as inhibition constant incubated for 90 mins by liquid scintillation spectrometry analysis
Measurement: Ki > 4000 nM (pChEMBL 5.3979997634887695)
Descriptors: MW 396.52, ALogP 3.82, HBA 6, HBD 0, PSA 62.47, QED 0.66
Compound (SMILES): NCc1cn([C@@H]2[C@@H](O[C@H]3C[C@H](C(=O)NCc4ccc(CO)cc4)[C@@H](C(=O)NCc4ccc(CO)cc4)C[C@@H]3OCCCl)O[C@H](CO)[C@@H](O)[C@@H]2O)nn1
InChIKey: BYGZQFCUFRSCML-RWSQSUCKSA-N
Target: C-type lectin domain family 4 member M (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2X3
Assay: Inhibition of DC-SIGN (unknown origin) by ITC assay
Measurement: Kd = 52000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 747.25, ALogP -0.63, HBA 14, HBD 8, PSA 243.77, QED 0.09
Compound (SMILES): O=C(Nc1nnn[nH]1)c1cc(-c2ccccc2)nc2ccccc12
InChIKey: OGLPTKDFYXRGBE-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 13800 nM (pChEMBL 4.860000133514404)
Descriptors: MW 316.32, ALogP 2.67, HBA 5, HBD 2, PSA 96.45, QED 0.61
Compound (SMILES): Cc1nc2c(c(-c3cc(C(N)=O)c(O)c4c3OCO4)cn2CC(=O)Nc2cc(N3CCN(C)C[C@@H]3C)nc(F)c2Cl)c(=O)n1C
InChIKey: CLOAUGDVBXEEFK-ZDUSSCGKSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 1.04 nM (pChEMBL 8.979999542236328)
Descriptors: MW 641.06, ALogP 2.21, HBA 12, HBD 3, PSA 170.07, QED 0.27
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C)c2)n1
InChIKey: QYMHHIWJCCQYPU-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.47, ALogP 5.09, HBA 5, HBD 2, PSA 71.42, QED 0.42
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCN6CCC(OC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: OYXCACHCXKHEOC-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 1025.6
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3cccc5ccccc35)C4=O)nn2)cc1
InChIKey: MWWVNAOGVSRMHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human transmembrane carbonic anhydrase 4 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 13.11 nM (pChEMBL 7.880000114440918)
Descriptors: MW 553.56, ALogP 3.23, HBA 9, HBD 1, PSA 154.55, QED 0.25
Compound (SMILES): COc1ccc(/C(=N\O)N2CCN(c3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: MMEGVAXNSOBAQE-CZIZESTLSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 739.1 nM (pChEMBL 6.130000114440918)
Descriptors: MW 390.46, ALogP 1.3, HBA 6, HBD 2, PSA 108.46, QED 0.35
Compound (SMILES): Cc1ccc2c(c1)c1cc[n+](-c3ccccc3)cc1n2C
InChIKey: ZWUSTXCHVYMQTF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) by Ellman's method
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 273.36, ALogP 3.92, HBA 1, HBD 0, PSA 8.81, QED 0.46
Compound (SMILES): COc1cc(/C=C/C(=O)[N-]S(=O)(=O)c2ccc(-n3nc(C(F)(F)F)cc3-c3ccc(C)cc3)cc2)ccc1[O-].[Na+].[Na+]
InChIKey: NMSJRWUGJMSTET-UHFFFAOYSA-L
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of COX1 (unknown origin)
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 557.55, ALogP 5.1, HBA 7, HBD 2, PSA 110.52, QED 0.31
Compound (SMILES): CC#CCOc1ccc2cc(C(O)(c3ccc(Br)cc3)c3cccnc3)oc2c1
InChIKey: GZWXDDIEDPOAKI-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate by LC-MS/MS analysis
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 448.32, ALogP 5.28, HBA 4, HBD 1, PSA 55.49, QED 0.42
Compound (SMILES): CC(C)n1c(=O)ccc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: DABVJURXDMIZKX-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 365.46, ALogP 1.21, HBA 7, HBD 1, PSA 97.19, QED 0.87
Compound (SMILES): COc1cc(Nc2nc(Nc3ccc(N4CCC(N(C)C)CC4)cc3OC)ncc2Cl)cc(B(O)O)c1
InChIKey: RHRGACFCHDEOQP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ALK cytoplasmic domain (1058 to 1620 residues) L1196M mutant expressed in baculovirus-infected Sf21 cells using LANCE Ultra ULight-PolyGT substrate incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 76.1 nM (pChEMBL 7.119999885559082)
Descriptors: MW 526.83
Compound (SMILES): O=C1NC(NC2CCCCCC2)=N/C1=C\c1ccc2ncsc2c1
InChIKey: HJEKFRDOAYXXRU-DHDCSXOGSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 340.45, ALogP 3.44, HBA 5, HBD 2, PSA 66.38, QED 0.65
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: QAMABQFUDMLHGO-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 4520 nM (pChEMBL 5.340000152587891)
Descriptors: MW 450.62, ALogP 6.42, HBA 5, HBD 1, PSA 54.7, QED 0.21
Compound (SMILES): N=C(N)NCCC[C@H](N)C(=O)NCC(=O)N[C@H](CCNC(=N)NCCSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)C(N)=O
InChIKey: CDHNSYFOBQQCHE-GBXCTRARSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of human PRMT4 by fluorescence-based SAHH-coupled assay
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 681.79, ALogP -5.06, HBA 15, HBD 13, PSA 356.43, QED 0.04
Compound (SMILES): CC1C(=O)N(C)CCN1c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: OJGOVIODTPNPDG-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (3 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 3 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 326.36, ALogP 0.42, HBA 7, HBD 1, PSA 95.83, QED 0.73
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)C(=O)C[C@@H](Cc1ccccc1)C(N)=O
InChIKey: SNHBRHBMEDWDNF-XIVIVISLSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49810
Assay: Inhibition of gamma-secretase (unknown origin)
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 671.88, ALogP 5.57, HBA 6, HBD 4, PSA 147.82, QED 0.14
Compound (SMILES): CN(C)Cc1ccc(C(=O)Nc2cc(-c3ccccc3)ccc2N)cc1
InChIKey: OFNZEWQMINRXML-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 345.45, ALogP 4.25, HBA 3, HBD 2, PSA 58.36, QED 0.68
Compound (SMILES): O=C1NCCN(C(=O)CCCN2CCN(c3cccc(Cl)c3Cl)CC2)C1C(=O)NCc1ccccc1
InChIKey: WJBZDMXLXHXOQF-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at human D4 receptor expressed in HEK293T cells assessed as inhibition of forskolin-induced cAMP production incubated for 1 hr by HTRF analysis
Measurement: IC50 = 870.96 nM (pChEMBL 6.059999942779541)
Descriptors: MW 532.47, ALogP 2.54, HBA 5, HBD 2, PSA 84.99, QED 0.51
Compound (SMILES): Cc1cc(-c2cnn(C)c2)cc([C@H]2CCN(C(=O)c3cc(C(C)C)n[nH]3)C2)n1
InChIKey: LNMSTPSCCSYARO-HNNXBMFYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: KDM5 Enzyme Assay: Full length KDM5A enzyme was expressed and purified inhouse. Biotin-H3K4me3 peptide was purchased from New England Biolabs. HTRF reagents (containing Eu-labeled H3K4me1-2 antibody, and streptavidin-XL665) were purchased from Cis-Bio International. Plates were read on an Envision multi-label plate reader (Perkin Elmer).The HTRF assay mixture contained 2 nM full length KDM5A enzyme, 100 nM H3K4Me3 peptide substrate, 1 uM 2-OG, 100 uM Fe2+, 500 uM ascorbate. 50 mM HEPES pH 7.0 buffer, 0.01% Triton-X 100, 2 mM DTT, 0.25% DMSO at a final volume of 10 uL.The enzyme reaction was carried out at room temperature in black Proxiplate 384-Plus plate (Corning. Costar) within 30 minutes, in the presence of varying concentration of a test compound. At the end of enzyme reaction, 5 uL of 1 mM EDTA were added to quench the reaction and then the detection reagents (5 uL) were added to give final concentrations of 0.5 nM Eu-labeled H3K4me1-2 antibody, and 50 nM streptavidin-XL665. The plates were incubated at room temperature for 60 minutes and then read in the Envision plate reader. The readouts were transformed into % inhibition, and IC50 value of a test compounds was generated by using four parameters curve fitting (Model 205 in XLFIT5, iDBS).
Measurement: IC50 = 0.17 nM (pChEMBL 9.770000457763672)
Descriptors: MW 378.48, ALogP 3.27, HBA 5, HBD 1, PSA 79.7, QED 0.76
Compound (SMILES): CC(=O)c1ccc(NC(=O)[C@H](Cc2ccccc2)NC(=O)C2CCC(CN)CC2)cc1
InChIKey: DLFGZBZOIOZRSV-FLJXZVEISA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of Urokinase (unknown origin)
Measurement: IC50 = 58000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 421.54, ALogP 3.32, HBA 4, HBD 3, PSA 101.29, QED 0.57
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(C(F)(F)F)cc3s2)CCN1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: HCKWZGBREFFBGT-KRWDZBQOSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 528, ALogP 5.58, HBA 6, HBD 1, PSA 65.9, QED 0.41
Compound (SMILES): Cc1cn(-c2ccc(Cl)cc2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: YUQSIOIGTXTCOF-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 362.84, ALogP 3.28, HBA 4, HBD 1, PSA 68.17, QED 0.78
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCN5CCCC5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: HBHOBCZCVGHUSQ-MASCHLQQSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 422.66, ALogP 5.48, HBA 3, HBD 0, PSA 15.71, QED 0.62
Compound (SMILES): NCc1cccc(-n2nc(C(N)=O)cc2C(=O)Nc2cc(C(NCC3CC3)c3ccccc3)ccc2F)c1
InChIKey: UMNCVWUVWBVXCX-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein using H-D-Pro-Phe-Arg-p-nitroaniline as substrate assessed as inhibition constant
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 512.59, ALogP 3.91, HBA 6, HBD 4, PSA 128.06, QED 0.26
Compound (SMILES): COc1ccc2c(c1)CN(c1nccc(Nc3ccc4[nH]ncc4c3)n1)C2
InChIKey: SWHUIIODYNUMNO-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Rho-kinase inhibition assay for ROC2 and ROCK1: Dose response curves for Rho-kinase inhibition were derived from a Invitrogen Z′-LYTE Kinase Assay Kit (Invitrogen catalog number PV3793). Purified active ROCK1 and ROCK2 were obtained from Invitrogen (catalog numbers ROCK1, PV3691 and ROCK2, PV3759). The kit components include a coumarin and fluorescein labeled peptide based on myosin light chain 2 (KKRPQRRYSNVF), a proprietary protease containing development reagent and a proprietary Stop buffer used to terminate the development reaction. The inhibitory activities of compounds are measured according to the manufactures protocol. Briefly, decreasing concentrations of test compounds or the known ROCK inhibitor Y-27963, are added, from 10 uM to 2.56×10−5 uM to reaction buffer containing 50 mM HEPES pH 7.5, 10 mM MgCl2, 5 mM EGTA, and 0.05% Brij-35 and of ROCK1 at 0.18 ug/mL or ROCK2 at 0.8 ug/mL in assay dilution buffer. This mixture is overlayed into a white 96-well half area plate and the reaction is initiated with the addition of 5 uM ATP for ROCK1 or 12 uM ATP for ROCK2. The assay proceeds at room temperature for 1 hour followed by the addition of development reagent, and further incubation for 1 hour at room temperature. STOP reagent is then added and the reaction and immediately the coumarin and fluorescein emission signals are read on a Tecan Infinite M1000 fluorescence plate reader (excitation: 400 nm; emission 445 and 520 nm, respectively). By comparing the emission ratios of the test samples against control samples, percent phosphorylation values are calculated and the concentration of inhibitor that produces ½ inhibition of kinase activity (IC50) is determined using Prism. Table 1 provides IC50 concentrations for compounds of the above examples. Several of the compounds also demonstrated activity in a preliminary assay that measured inhibition of myosin light chain phosphorylation (pMLC). For compounds marked ND, activity was not determinable under the test conditions employed.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 358.41, ALogP 3.63, HBA 6, HBD 2, PSA 78.96, QED 0.58
Compound (SMILES): CN1CCN(CCOC(=O)c2ccc3ccccc3c2)CC1
InChIKey: XANINQRTAHTGQS-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity to human D3 receptor expressed in CHO cells assessed as inhibition constant by scintillation counting method
Measurement: Ki > 10 nM (pChEMBL 8)
Descriptors: MW 298.39, ALogP 2.24, HBA 4, HBD 0, PSA 32.78, QED 0.81
Compound (SMILES): Cc1c(Cl)c(=O)oc2cc(OCCCSC(=S)N3C(C)CCCC3C)ccc12
InChIKey: JLHNPMPZJUKIDO-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 440.03, ALogP 5.8, HBA 5, HBD 0, PSA 42.68, QED 0.33
Compound (SMILES): COc1cccc(Cc2cc(C)nn([C@@H](C)C(=O)Nc3ccc(Cl)cc3)c2=O)c1
InChIKey: JQMCPEBDJPMQGI-HNNXBMFYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Agonist activity at human recombinant FPR1 stably transfected in Flp-In-CHO cells assessed as ERK1/2 phosphorylation incubated for 1 hr by Alphascreen fluorescence assay
Measurement: EC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 411.89, ALogP 4, HBA 5, HBD 1, PSA 73.22, QED 0.66
Compound (SMILES): CC1(C)CN(c2ccc(-c3ccccc3P(C)(C)=O)c(F)c2F)C(=O)[C@@H]1NC(=O)Nc1cnc(Cl)cn1
InChIKey: OTLMDKSLNKNQJK-QFIPXVFZSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at human FPR2 expressed in CHO cells assessed as cAMP level incubated for 1.5 hr by HTRF assay
Measurement: EC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 547.93, ALogP 4.89, HBA 5, HBD 2, PSA 104.29, QED 0.44
Compound (SMILES): NCCCCCCCCN1CCC(OC(=O)Nc2ccc(F)cc2-c2ccc(F)c(Cl)c2)CC1
InChIKey: FPCBWBHSQIVWBN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 494.03, ALogP 6.6, HBA 4, HBD 2, PSA 67.59, QED 0.35
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)CC1
InChIKey: QSUSOTUHCHGTAN-RRPNLBNLSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 613.58, ALogP 3.41, HBA 7, HBD 2, PSA 105.9, QED 0.32
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)CC1
InChIKey: CTYFJJGDZUXTIC-SXOMAYOGSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 602.68, ALogP 3.67, HBA 7, HBD 2, PSA 105.9, QED 0.33
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccco1
InChIKey: PWUHEYLDBRSIRJ-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.94, ALogP 4.64, HBA 5, HBD 1, PSA 88.85, QED 0.6
Compound (SMILES): C[C@@H]1CCN(C(=O)N2CCCCC2)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
InChIKey: DMASMODATALSAD-CJNGLKHVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 382.47, ALogP 2.69, HBA 4, HBD 2, PSA 90.02, QED 0.68
Compound (SMILES): Cc1cn(-c2cncc(C(F)(F)F)c2)c2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc12
InChIKey: AQAQROFTSRFYID-UHFFFAOYSA-N
Target: Sodium channel protein type 1 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 441.41, ALogP 3.71, HBA 5, HBD 1, PSA 81.06, QED 0.63
Compound (SMILES): CC(C)=CCc1ccc(O)c(C(=O)c2c(O)cc(C)cc2C(=O)C(C)C)c1O
InChIKey: YYPXPFQWFRXFCA-UHFFFAOYSA-N
Target: Sterol O-acyltransferase 1 (SINGLE PROTEIN), Chlorocebus aethiops
UniProt: O77760
Assay: Inhibition of african green monkey SOAT1 expressed in CHO cells assessed as reduction cholesteryl ester synthesis
Measurement: IC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 382.46, ALogP 4.69, HBA 5, HBD 3, PSA 94.83, QED 0.5
Compound (SMILES): CC(C)n1nc(C(=O)NC2CCN(CC(C)(C)CO)CC2)c2ccccc21.Cl
InChIKey: PMJILQKGBKOQNX-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 372.51, ALogP 2.83, HBA 5, HBD 2, PSA 70.39, QED 0.82
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-SXOMAYOGSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: WWKQQRVQGOUIMX-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 5190 nM (pChEMBL 5.289999961853027)
Descriptors: MW 436.6, ALogP 6.03, HBA 5, HBD 1, PSA 54.7, QED 0.25
Compound (SMILES): COCCCC(=O)N(C)CCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: FKEYBQUXJBIQQC-GNAFDRTKSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Antagonist activity against recombinant human adrenergic alpha1A receptor expressed in Rat1 cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 511.07, ALogP 3.99, HBA 6, HBD 0, PSA 67.67, QED 0.36
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc(C)[nH]c2c1=O
InChIKey: POICMTYCJMMADL-ONEGZZNKSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged BRD4 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 391.47, ALogP 3.35, HBA 4, HBD 1, PSA 67.33, QED 0.69
Compound (SMILES): Cc1c(C(=O)N[C@H](CCC2CC2)C(=O)Nc2ccc(C#N)cc2)[nH]c2c1C(=O)CC(C)(C)C2
InChIKey: OWORSODZTADOQX-LJQANCHMSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of N-terminal GST-tagged human recombinant G9a (785 to 1210 residues) expressed in baculovirus infected Sf9 cells incubated for 1 hr by AlphaLISA analysis
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 446.55, ALogP 4.28, HBA 4, HBD 3, PSA 114.85, QED 0.59
Compound (SMILES): CC(C)(O)c1ccc(-c2cn3c(F)c(F)cc3c(=O)[nH]2)cc1
InChIKey: OKVSYWJACIIIKC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 304.3, ALogP 2.8, HBA 3, HBD 2, PSA 57.5, QED 0.76
Compound (SMILES): CS(=O)(=O)Nc1ccccc1-c1ccc(N2CCC[C@@H](NC(=O)Nc3ccc(Cl)cc3)C2=O)cc1
InChIKey: LOSIFPMBGPRRNJ-HSZRJFAPSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: cAMP Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays. A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 flurorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm.
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 513.02, ALogP 4.7, HBA 4, HBD 3, PSA 107.61, QED 0.44
Compound (SMILES): O=C1NCCc2c1cnn2-c1ccnc(Cc2cc(F)cc(C(F)(F)F)c2)c1
InChIKey: VASPFLVEEOBQOS-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by automated patch-clamp assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.34, ALogP 3.3, HBA 4, HBD 1, PSA 59.81, QED 0.7
Compound (SMILES): C/C=C1\NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)C/C(C)=C/Cl)[C@@H](C)CC)[C@@H](C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc2ccc(O)cc2)N(C)C(=O)[C@H](Cc2ccccc2)N2C(=O)[C@H](CC[C@H]2O)NC1=O
InChIKey: CWLDDHHTMAJFMM-LKVOOIPRSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of elastase in human neutrophil using N-(OMe-succinyl)-Ala-Ala-Pro-Val-p-nitroanilide as substrate preincubated with enzyme for 15 mins followed by substrate addition and measured every 30s for 30 mins by absorbance based analysis
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 1021.61
Compound (SMILES): Cc1cc(=O)c(O)c(CO)n1CCCn1cc(COc2cc3ccccc3oc2=O)nn1
InChIKey: KGEFCJWVCMQACO-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19643
Assay: Inhibition of rat brain mitochondria MAO-B using p-tyramine as substrate incubated for 15 mins by Amplex Red reagent and horseradish peroxidase based fluorometric analysis
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 438.44, ALogP 1.72, HBA 10, HBD 2, PSA 132.61, QED 0.4
Compound (SMILES): COc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: HRRLKCWFIQQCIC-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 447.47, ALogP 2.26, HBA 8, HBD 1, PSA 142.07, QED 0.56
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3ncccc3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: HENRITOGWFFGGA-PMACEKPBSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 2557 nM (pChEMBL 5.590000152587891)
Descriptors: MW 539.57, ALogP 3.38, HBA 9, HBD 3, PSA 150.28, QED 0.32
Compound (SMILES): COc1ccc(CNCCCCCCC(=O)NO)cc1OC
InChIKey: IQGSZEFWMXKAJG-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant HDAC3 expressed in baculovirus by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 310.39, ALogP 2.25, HBA 5, HBD 3, PSA 79.82, QED 0.33
Compound (SMILES): O=C(Nc1cnccc1Oc1ccccc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: QORWUQJNIZUKNZ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 374.4, ALogP 3.87, HBA 5, HBD 2, PSA 93.21, QED 0.68
Compound (SMILES): O=C(Cc1ccccc1)N1CCN(c2ccc(O)cc2)CC1
InChIKey: VEAAIEOUCDGSDL-UHFFFAOYSA-N
Target: NADP-dependent malic enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P48163
Assay: Inhibition of His-tagged human recombinant full length ME1 using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 296.37, ALogP 2.28, HBA 3, HBD 1, PSA 43.78, QED 0.94
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: RXAZQWJCOUIOPS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 19 Deletion and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR exon 19 deletion and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 19 deletion and T790M mutation. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR E746-A750 deletion and T790M Mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 19 deletion and T790M mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR E746-A750 deletion and T790M Mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR E746-A750 deletion and T790M Mutation (named Ba/F3-EGFR-Del/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR-Del/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 557.66, ALogP 4.3, HBA 10, HBD 2, PSA 113.85, QED 0.21
Compound (SMILES): Nc1ncc(-c2cc(N3C[C@@H]4C[C@H]3CO4)nc(N3CC4CC3C4)n2)nc1C(F)(F)F
InChIKey: QUJWSXIGZUDUAB-QQFIATSDSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 323 nM (pChEMBL 6.489999771118164)
Descriptors: MW 419.41, ALogP 2.11, HBA 8, HBD 1, PSA 93.29, QED 0.81
Compound (SMILES): Cc1cc2c(=O)[nH]c(-c3ccc(C(C)(C)O)cc3)cn2n1
InChIKey: HJVQHFYHONMFDN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) using biotinylated NAD and NAD as substrate assessed as inhibition of auto-PARsylation incubated for 150 mins by TR-FRET assay
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 283.33, ALogP 2.23, HBA 4, HBD 2, PSA 70.39, QED 0.76
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CN(CC[C@H](N)C(=O)O)S(=O)(=O)c2cnc(Cl)cn2)[C@@H](O)[C@H]1O
InChIKey: NUFHSMQFUWVWAB-ACSHICKMSA-N
Target: tRNA (cytosine(38)-C(5))-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: O14717
Assay: Binding affinity to full-length human DNMT2 expressed in bacteria assessed as apparent dissociation constant by ITC method
Measurement: Kd = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 543.95, ALogP -2.04, HBA 14, HBD 5, PSA 245.79, QED 0.2
Compound (SMILES): N#CC(c1ccc(F)cc1)c1cccc(C(F)(F)F)n1
InChIKey: DXQNDKQUHKVTTC-UHFFFAOYSA-N
Target: Acyl-homoserine lactone acylase PvdQ (SINGLE PROTEIN), Pseudomonas aeruginosa (strain LESB58)
UniProt: Q9I194
Assay: Competitive inhibition of Pseudomonas aeruginosa ATCC 15692 pvdQ
Measurement: Ki = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 280.22, ALogP 3.89, HBA 2, HBD 0, PSA 36.68, QED 0.78
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)c1csc(Nc2ccccc2)n1
InChIKey: CYVGSDYVNUNREA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 89.6 nM (pChEMBL 7.050000190734863)
Descriptors: MW 335.39, ALogP 4.02, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): CCC[C@H](C)Oc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(OC)ccc2OC)c1C
InChIKey: LCZDEXFSZLWZDC-KRWDZBQOSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 480.61, ALogP 5.71, HBA 7, HBD 1, PSA 87.5, QED 0.42
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CC4)c3)c2n1
InChIKey: HBAQYPYDRFILMT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 364.41, ALogP 1.36, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): CCCCCCNNC(=O)c1ccc(Br)cc1
InChIKey: YQIPSZXUSOVGKH-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 16110 nM (pChEMBL 4.789999961853027)
Descriptors: MW 299.21, ALogP 3.26, HBA 2, HBD 2, PSA 41.13, QED 0.6
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3ccc(-c4ccc[nH]4)nn3)C3CCN2CC3)c1
InChIKey: ZKWHETNMJXBGTO-CTNGQTDRSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Binding affinity to alpha3beta4 nAChR (unknown origin) assessed as dissociation constant
Measurement: Ki = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 361.45, ALogP 2.95, HBA 5, HBD 1, PSA 66.93, QED 0.76