lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4ccccc4)cs3)cs2)cc(OC)c1
InChIKey: OOGDXDOGQSAONV-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 = 1081 nM (pChEMBL 5.96999979019165)
Descriptors: MW 395.51, ALogP 5.69, HBA 7, HBD 1, PSA 56.27, QED 0.45
Compound (SMILES): O=S(=O)(NCCCNc1nccc(-c2c(-c3cccc(F)c3)nc3occn23)n1)c1ccccc1
InChIKey: DMEBBSDHOMWAOU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-RAF V600E mutant (unknown origin) expressed in HEK293 cells in presence of tracer incubated for 1 hr by NanoBRET assay
Measurement: IC50 = 0.034 nM (pChEMBL 10.470000267028809)
Descriptors: MW 492.54, ALogP 3.97, HBA 8, HBD 2, PSA 114.42, QED 0.3
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(OC(F)F)cc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: DKVBUSZSQFOSNU-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 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 424.41, ALogP 4.35, HBA 5, HBD 2, PSA 93.21, QED 0.59
Compound (SMILES): COC1=CC(=O)C=C([S@@+]([O-])c2ccc(C)cc2)C1=O
InChIKey: QKSHRPJNIFGBBQ-IBGZPJMESA-N
Target: M-phase inducer phosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P30307
Assay: Inhibition of human CDC25C
Measurement: IC50 = 5720 nM (pChEMBL 5.239999771118164)
Descriptors: MW 276.31, ALogP 1.67, HBA 4, HBD 0, PSA 66.43, QED 0.62
Compound (SMILES): CCCOc1cc(-c2nc(C3COB(O)C3)ns2)ccc1OC
InChIKey: LBADOWKZXSXFPE-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4 catalytic domain expressed in Escherichia coli
Measurement: IC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 334.21
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(NS(=O)(=O)c3cccs3)ccc21
InChIKey: FCIGWHAAHQIDME-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 = 9260 nM (pChEMBL 5.03000020980835)
Descriptors: MW 388.47, ALogP 3.73, HBA 5, HBD 1, PSA 79.62, QED 0.74
Compound (SMILES): O=C(CN1CCN(c2ccc(O)cc2)CC1)Nc1ccccc1
InChIKey: IXKBNMZSPYLPLY-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 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 311.39, ALogP 2.15, HBA 4, HBD 2, PSA 55.81, QED 0.91
Compound (SMILES): Fc1ccc(CN2CCCC3(CCN(Cc4cc5ccc(Cl)cc5[nH]4)C3)C2)cc1F
InChIKey: JGUJMJSODMVSHV-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 429.94, ALogP 5.59, HBA 2, HBD 1, PSA 22.27, QED 0.58
Compound (SMILES): CS(=O)(=O)n1cc(COc2ccc3[nH]ccc3c2)c2cc(C(=O)OCc3cc(C#N)[nH]c(=O)c3)ccc21
InChIKey: ILUBXGLQULCOCH-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of human recombinant His6 tagged SENP1 catalytic domain expressed in Escherichia coli BL21 (DE3) using SUMO2-AMC as substrate incubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 516.54, ALogP 3.43, HBA 8, HBD 2, PSA 147.04, QED 0.32
Compound (SMILES): O=c1oc2cc(O)c(O)cc2c2c(-c3ccc(O)c(O)c3)cn(CCc3ccc(O)c(O)c3)c12
InChIKey: KXHHKZGXANWIJQ-UHFFFAOYSA-N
Target: Casein kinase I isoform delta (SINGLE PROTEIN), Homo sapiens
UniProt: P48730
Assay: Inhibition of N-terminal GST-tagged human recombinant CK1delta (1 to 294 residues) expressed in Escherichia coli incubated for 60 mins in presence of ATP by Kinase-glo luminescent assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 461.43, ALogP 3.89, HBA 9, HBD 6, PSA 156.52, QED 0.17
Compound (SMILES): CCN(c1ccc(C(=O)O)cc1)c1ccc(C(C)C)c(OCC(C)C)c1
InChIKey: IEXWAKMGEJFXBF-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Inhibition of RXRgamma (unknown origin)
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 355.48, ALogP 5.7, HBA 3, HBD 1, PSA 49.77, QED 0.66
Compound (SMILES): CCc1c(F)ccc2cc(O)cc(-c3ncc4c(N5CC(O)CC6(CC6)C5)nc(OC[C@@]56CCCN5C[C@H](F)C6)nc4c3F)c12
InChIKey: VMQIRFRPHWDRTL-VLNKEHDUSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12D mutant in human ASPC1 cells assessed as reduction in ERK1/2 phosphorylation level incubated for 2 hrs by MSD assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 619.69, ALogP 5.7, HBA 8, HBD 2, PSA 94.84, QED 0.28
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 250 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): COc1cc2c(Nc3cccc(/C=C/C(=O)NO)c3)ncnc2cc1OCCCN1CCOCC1
InChIKey: TZKQSNHUWVISSS-VOTSOKGWSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 479.54, ALogP 3, HBA 9, HBD 3, PSA 118.07, QED 0.17
Compound (SMILES): c1cncc(C[C@@H]2[C@@H](Oc3cc4ccccc4cn3)C3CCN2CC3)c1
InChIKey: KHRMJWYROCGIKU-IRLDBZIGSA-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 = 2150 nM (pChEMBL 5.670000076293945)
Descriptors: MW 345.45, ALogP 3.71, HBA 4, HBD 0, PSA 38.25, QED 0.72
Compound (SMILES): COc1cccc(C2(O)CCN(C(=O)Cc3cc(C(F)(F)F)cc(C(F)(F)F)c3)CC2CN(C)C)c1
InChIKey: XNAKXLRXFMCFJH-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 = 4424 nM (pChEMBL 5.349999904632568)
Descriptors: MW 518.5, ALogP 4.57, HBA 4, HBD 1, PSA 53.01, QED 0.57
Compound (SMILES): COc1cc(Nc2nc(-c3nc(-c4cccc(Cl)c4)cs3)cs2)cc(OC)c1
InChIKey: UTRROKDEYSMRLE-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 = 7546.1 nM (pChEMBL 5.119999885559082)
Descriptors: MW 429.95, ALogP 6.35, HBA 7, HBD 1, PSA 56.27, QED 0.39
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Macaca fascicularis
UniProt: Q2XVA1
Assay: Inhibition of cynomolgus monkey CYP17A1
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): Cc1ccc(NCC[C@@H]2CCCN3CCCC[C@H]23)c2c(=O)c3ccccc3oc12
InChIKey: DALMBCBRULLIPO-GHTZIAJQSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of self-induced amyloid beta (unknown origin) aggregation
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 390.53, ALogP 5.32, HBA 4, HBD 1, PSA 45.48, QED 0.61
Compound (SMILES): CN1CC2CCC(C1=O)C2c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: NRBSFHSUWBAYCI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant human FGFR4 (460 to 802 residues) using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 351 nM (pChEMBL 6.460000038146973)
Descriptors: MW 337.39, ALogP 1.34, HBA 6, HBD 1, PSA 92.59, QED 0.76
Compound (SMILES): CCCCOc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(Br)ccc2OC)c1C
InChIKey: ZPMZOVYHLLEGCD-UHFFFAOYSA-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 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 515.45, ALogP 6.08, HBA 6, HBD 1, PSA 78.27, QED 0.37
Compound (SMILES): C[C@@]12CC[C@@H]3[C@@](CC[C@H]4[C@@]3(C)CCC[C@@]4(C)C(=O)OCc3ccccc3I)(CC1=O)C2
InChIKey: YCRLFZVWDDADLI-FIVJYGDRSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of CDC25B (unknown origin) by DAS-ELISA
Measurement: IC50 = 3240 nM (pChEMBL 5.489999771118164)
Descriptors: MW 534.48, ALogP 6.71, HBA 3, HBD 0, PSA 43.37, QED 0.32
Compound (SMILES): CN1Cc2ccc(Nc3ncc4c(=O)c(-c5c(Cl)cccc5Cl)cn(C)c4n3)cc2C1
InChIKey: VWMUXXQYMWYAAA-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 = 173 nM (pChEMBL 6.760000228881836)
Descriptors: MW 452.35, ALogP 4.99, HBA 6, HBD 1, PSA 63.05, QED 0.47
Compound (SMILES): COc1cc(Nc2nc(-c3nccs3)cs2)cc(OC)c1
InChIKey: SWDMSJVRZISODY-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 = 88.96 nM (pChEMBL 7.050000190734863)
Descriptors: MW 319.41, ALogP 4.03, HBA 7, HBD 1, PSA 56.27, QED 0.77
Compound (SMILES): CC1(C(=O)NS(=O)(=O)c2ccc(Cl)s2)CCN(c2nc3c(cc2C#N)C(=O)OC3)CC1
InChIKey: OTWUQESYHAXXJO-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 7750 nM (pChEMBL 5.110000133514404)
Descriptors: MW 480.96, ALogP 2.45, HBA 9, HBD 1, PSA 129.46, QED 0.66
Compound (SMILES): COc1ccc2c(c1)c(Cc1nonc1O)c(C)n2C(=O)c1ccccc1
InChIKey: DKXLGDJKCXEKTB-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 363.37, ALogP 3.33, HBA 7, HBD 1, PSA 90.38, QED 0.6
Compound (SMILES): CC(C)(C)c1ccc(-n2cnc3c(NC(=O)Cc4ccc(C(=O)O)cc4)cccc32)cc1
InChIKey: VEHCUCLQBZOABJ-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Antagonist activity at FXR-LBD-GST (unknown origin) in presence of GW4064
Measurement: IC50 = 20700 nM (pChEMBL 4.679999828338623)
Descriptors: MW 427.5, ALogP 5.2, HBA 4, HBD 2, PSA 84.22, QED 0.46
Compound (SMILES): Cc1cccc(-c2c(C)cc3c(nc(N4CC(C)(N(C)C)C4)c4nnn([C@H]5CCN(C(=O)/C=C/CF)[C@H](CC#N)C5)c43)c2F)c1Cl
InChIKey: SGKJCEWPMPNTKX-ROOIWUQASA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human MIA PaCa-2 cells assessed as reduction in whole blood pERK level incubated for 4 hrs by HTRF assay
Measurement: IC50 <= 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 647.17, ALogP 6.17, HBA 8, HBD 0, PSA 94.18, QED 0.22
Compound (SMILES): Cn1nc(-c2ccnc(N)n2)c2cc(C#CC(C)(C)O)ccc21
InChIKey: QOLYGQOTGMKVNP-UHFFFAOYSA-N
Target: Tau-tubulin kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TCY1
Assay: Inhibition of TTBK1 in human HEK293T cells incubated for 1 hrs by HTRF assay
Measurement: IC50 = 1415 nM (pChEMBL 5.849999904632568)
Descriptors: MW 307.36, ALogP 1.73, HBA 6, HBD 2, PSA 89.85, QED 0.67
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@@H](C(C)C)C2)c1
InChIKey: RVZUBLMVVIWYLZ-OAQYLSRUSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha 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 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 491.58, ALogP 5.6, HBA 5, HBD 1, PSA 56.67, QED 0.49
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(F)cc1Cl)c1ccnc(NC(=O)C2CC2)c1
InChIKey: CCLYDGMRCYZTFK-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 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 410.84, ALogP 4.54, HBA 4, HBD 2, PSA 83.98, QED 0.65
Compound (SMILES): CCNCc1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: RGHPABLOPKTYRU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human Jurkat cells assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 364.43, ALogP 3.58, HBA 5, HBD 2, PSA 71.42, QED 0.57
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4cccnc4)c(-c4c(Cl)ccc5[nH]ncc45)c3C)C2)C1
InChIKey: GPSWEICMVSMBQY-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Scintillation Proximity Assay (SPA): Assays were run using 384-well plates (781207/Greiner) in which one column was designated as the high signal (no inhibition) control, and contained DMSO with no test compound, and another column was designated as the low signal control (maximal inhibition), and contained no protein. Serial dilutions of compounds to be tested were added to the assay plate (resulting in duplicate 11-point dose response with semi-log compound dilutions from 50 μM to 0.5 nM or from 5 μM to 0.05 nM for the most potent compounds). A 1/20 isotopic dilution of labeled (Compound B) and non-labeled covalent (Compound A) probe was prepared and added to all wells on the plate. The reaction was started by addition of KRasG12C (M1-K169, biotinylated on the N-terminus) to the compounds and incubated for 2 hours with continuous agitation allowing for full modification of KRasG12C with probe or test compounds. Final concentrations in an assay volume of 40 μL were 10 nM KRasG12C, 25 nM radio-ligand and 475 nM unlabelled ligand. The assay buffer contained 20 mM Tris-HCl pH 7.5 (Invitrogen), 150 mM NaCl (Sigma Aldrich), 0.1 mM MgCl2 (Sigma Aldrich), and 0.01% Tween-20 (Sigma Aldrich). Following addition of 50 μL of a 400 μg/ml. suspension of streptavidin-coated YSi beads (Perkin Elmer), plates were incubated for a further 30 min with continuous agitation before reading the plates on a scintillation counter (Topcount NXT 384 (Packard).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 458.95, ALogP 4.8, HBA 5, HBD 1, PSA 79.7, QED 0.45
Compound (SMILES): CC(C)(C)N1C=CN(C(=O)CCCN2CCN(c3cccc(Cl)c3Cl)CC2)CC1=O
InChIKey: VXJVZBXRTNKKRU-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 = 1148.15 nM (pChEMBL 5.940000057220459)
Descriptors: MW 453.41, ALogP 3.84, HBA 4, HBD 0, PSA 47.1, QED 0.68
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)c1
InChIKey: YQXARSVRDPJIEQ-NCSHYYEOSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 518.56, ALogP 4.43, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): c1csc(-c2csc(Nc3ccc(Cn4cncn4)cc3)n2)n1
InChIKey: DWOIASDYIGUZCD-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 = 140.8 nM (pChEMBL 6.849999904632568)
Descriptors: MW 340.44, ALogP 3.65, HBA 8, HBD 1, PSA 68.52, QED 0.6
Compound (SMILES): COC/C=C/C(=O)N1CC[C@H](n2nnc3c(O[C@@H](C)[C@@H]4CCCN4C)nc4c(F)c(-c5ccc(F)cc5)c(C)cc4c32)C[C@H]1CC#N
InChIKey: XGRLMSXYUVRMAB-TVLFMIPYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human MIA PaCa-2 cells assessed as reduction in whole blood pERK level incubated for 4 hrs by HTRF assay
Measurement: IC50 <= 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 643.74, ALogP 5.74, HBA 9, HBD 0, PSA 109.4, QED 0.21
Compound (SMILES): CN(C)CCCNc1nc(NC2CCN(Cc3ccccc3)CC2)c2ccccc2n1
InChIKey: OVNOBEWSTIRPLG-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Binding affinity to LSD1 (unknown origin) assessed as inhibition constant
Measurement: Ki = 1059 nM (pChEMBL 5.96999979019165)
Descriptors: MW 418.59, ALogP 4.07, HBA 6, HBD 2, PSA 56.32, QED 0.51
Compound (SMILES): COc1cccc(F)c1-c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: CGNKHHSWDZOKRN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μl of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech).
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 324.32, ALogP 2.57, HBA 6, HBD 1, PSA 81.51, QED 0.63
Compound (SMILES): Cc1nc2c(c(-c3cc(C(N)=O)c(O)c(F)c3F)cn2CC(=O)Nc2cc(N3CCN(C)C[C@@H]3C)ncc2Cl)c(=O)n1C
InChIKey: JJACRWNCVAHDPS-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 = 47.2 nM (pChEMBL 7.329999923706055)
Descriptors: MW 615.04, ALogP 2.62, HBA 10, HBD 3, PSA 151.61, QED 0.3
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CCc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: MDHIFDZZMWLNKL-WZOWOQAZSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from kappa opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 456.59, ALogP 3.93, HBA 5, HBD 0, PSA 42.01, QED 0.52
Compound (SMILES): Cc1noc(-c2ccccc2)c1C#CCCCCCNC(=O)C(C)(C)S
InChIKey: AUWLDIJACPXDCN-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 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 370.52, ALogP 4.39, HBA 4, HBD 2, PSA 55.13, QED 0.43
Compound (SMILES): C[N+]1=C(/C=C/C=C/C=C2\N(CCCCCC(=O)NCCCCCCn3cc(CCCCN4CCC5(CC4)OCc4ccccc45)c4ccccc43)c3ccccc3C2(C)C)C(C)(C)c2ccccc21.[I-]
InChIKey: PYGSKQVDDNNOJX-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of (+)-pentazocine from sigma 1 receptor in human MCF7 cells assessed as dissociation constant in presence of DTG incubated for 120 mins by saturation binding assay
Measurement: Kd = 13.59 nM (pChEMBL 7.869999885559082)
Descriptors: MW 925.34, ALogP 13.22, HBA 5, HBD 1, PSA 52.75, QED 0.05
Compound (SMILES): Oc1cc(Cl)c(C2CC2)c(-c2ncc3c(N4CCCC5(CCO5)C4)nc(OC[C@@]45CCCN4C[C@H](F)C5)nc3c2F)c1
InChIKey: UOFIDBDQKPLOIA-NMBBPYNWSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12D mutant in human ASPC1 cells assessed as reduction in ERK1/2 phosphorylation level incubated for 2 hrs by MSD assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 598.09, ALogP 5.78, HBA 8, HBD 1, PSA 83.84, QED 0.38
Compound (SMILES): O=C(CCc1ccc(-c2ccccc2)s1)N1CCN(c2ccc(O)cn2)CC1
InChIKey: NMCOMGYGVBTNMG-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 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 393.51, ALogP 3.8, HBA 5, HBD 1, PSA 56.67, QED 0.72
Compound (SMILES): CCOC(=O)c1ncc2[nH]c3ccc(O)cc3c2c1COC
InChIKey: VJVAWKPXJCDEQG-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P34903
Assay: Binding affinity to human recombinant GABAA alpha3 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 300.31, ALogP 2.74, HBA 5, HBD 2, PSA 84.44, QED 0.72
Compound (SMILES): Cc1cnc2c(c1)c(Nc1cnccc1C(=O)O)cn2CCN1CCC(F)(F)CC1
InChIKey: KDYQCOVJKZYFKX-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of KDM4C (unknown origin) incubated for 20 mins by Alphascreen assay
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 415.44, ALogP 3.91, HBA 6, HBD 2, PSA 83.28, QED 0.64
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: OHTCHFUKVDURAI-MMDZAOKXSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Inhibition of human somatostatin receptor type 3
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 621.74, ALogP -0.09, HBA 7, HBD 8, PSA 221.53, QED 0.1
Compound (SMILES): c1ccc(-c2nnc(O[C@H]3C4CCN(CC4)[C@@H]3Cc3cccnc3)s2)cc1
InChIKey: VTNUIOCYBBUEHK-MOPGFXCFSA-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 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 378.5, ALogP 3.68, HBA 6, HBD 0, PSA 51.14, QED 0.68
Compound (SMILES): CC(C)N1CCC(c2nnc(-c3nn(C(C)C)c4ccccc34)o2)CC1
InChIKey: HUYJRMFAFYNTRY-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 353.47, ALogP 4.26, HBA 6, HBD 0, PSA 59.98, QED 0.7
Compound (SMILES): CCOC(=O)c1sc2[nH]cn/c(=N\[C@H]3CCN(CC)C3)c2c1C
InChIKey: PLEPSJGJESSGQG-NSHDSACASA-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 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 334.45, ALogP 2.1, HBA 6, HBD 1, PSA 70.58, QED 0.87
Compound (SMILES): O=C1NCc2c(Cl)cc3c(-c4ccccc4)c[nH]c3c21
InChIKey: IWKDQQIVXBSVBE-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of human CLK2
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 282.73, ALogP 3.73, HBA 1, HBD 2, PSA 44.89, QED 0.7
Compound (SMILES): CCc1c(C(=O)OC)nc(C)c2[nH]c3cc(OC)c(OC)cc3c12
InChIKey: NHJRHDMRNNOSLV-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P34903
Assay: Binding affinity to human recombinant GABAA alpha3 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 328.37, ALogP 3.39, HBA 5, HBD 1, PSA 73.44, QED 0.74
Compound (SMILES): C=CC(=O)N1CCCCCCn2cc(c3ccccc32)-c2ccnc(n2)Nc2cc1ccc2F
InChIKey: NZQVBVJVPVPNFS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant (unknown origin)
Measurement: IC50 = 6.49 nM (pChEMBL 8.1899995803833)
Descriptors: MW 455.54, ALogP 6.07, HBA 5, HBD 1, PSA 63.05, QED 0.35
Compound (SMILES): COc1cc(C)c(Cl)cc1S(=O)(=O)Nc1ccc2c(c1)CCCN2C(=O)c1ccc(C)cc1
InChIKey: ZMRYYAYXNFIDRW-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 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 485.01, ALogP 5.36, HBA 4, HBD 1, PSA 75.71, QED 0.53
Compound (SMILES): Cc1c(Oc2ccc(CN)cc2F)ccc2c1B(O)OC2
InChIKey: ZCITXZXBLWIHHP-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Competition Binding Assay: Phosphorylation of activity of ROCK1 and ROCK2 and those of other kinases, AKT1, GRK2, PKA, PKCa and RSK1 were performed by Reaction Biology (Malvern, Pa.) (Ma et al., 2008) The ROCK1 enzyme tested was GST[1-535] ROCK1 (Genbank, NP 005397), ROCK2 was GST[5-554] (Genbank, 3327051). For the kinase assay buffers contained 20 mM Hepes, 10 mM MgCl2, 2 mM DTT, 0.02 mg/mL BSA, 0.1% DMSO, 1 mM EGTA, 0.02% Brij-35, 10 uM ATP, [γP33]-ATP and for ROCK enzymes, 20 uM long S6-peptide (32 amino acids length). Appropriate substrates and activation was applied for the other kinases tested. Each enzyme was preincubated with test compound for 15 min., and the reaction started by addition of ATP. Samples were incubated at room temperature for 120 min, and applied to P81 ion exchange paper and washed extensively; the radioactive content of the filters were determined.
Measurement: IC50 = 9.25 nM (pChEMBL 8.029999732971191)
Descriptors: MW 287.1
Compound (SMILES): N#Cc1cn(CCCc2ccccc2)c2c(N3CCN(CCc4c[nH]c5ccccc45)CC3)ncnc12
InChIKey: YKKLHDHOUSXZOO-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP (unknown origin) expressed in dog MDCK-II cells using pheophorbide A as substrate preincubated for 20 mins followed by substrate addition and measured after 120 mins by flow cytometry analysis
Measurement: IC50 = 1690 nM (pChEMBL 5.769999980926514)
Descriptors: MW 489.63, ALogP 4.78, HBA 6, HBD 1, PSA 76.77, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)CC1
InChIKey: LNJMXIZSFNEQQF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA analysis
Measurement: IC50 = 18.7 nM (pChEMBL 7.730000019073486)
Descriptors: MW 432.48, ALogP 3.08, HBA 7, HBD 2, PSA 123.04, QED 0.48
Compound (SMILES): Cc1ccccc1/N=N/c1cc(S(=O)(=O)O)c2ccccc2c1N
InChIKey: PIWJSAOBFMHEAW-FMQUCBEESA-N
Target: Sentrin-specific protease 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC62
Assay: Binding Assay: The binding of SPI-01 to the enzyme-substrate complex was investigated. CSP analysis was carried out on the 40 kDa complex of 15N-labeled full length precursor SUMO-1-GGHSTV (SUMO-1-FL) with unlabeled SENP1-C603S. An equimolar amount of SPI-01 was added to the 1:1 enzyme-substrate complex. The only observed CSP on the 15N-labeled precursor SUMO-1-FL was on the C-terminal residues S99 and V101 (FIGS. 7 and 8) (Song et al., PNAS 101:14373-8 (2004)). This result indicates that SPI-01 binds the enzyme-substrate complex at the interface between SENP and the C-terminal tails of precursor SUMO-FL. X-ray crystal structures showed that the C-terminal tail of precursor SUMO sits in and projects out of the catalytic tunnel of SENPs (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006)). In the case of SENP1, the region that interacts with the projected C-terminus is predominantly acidic and favors the C-terminus of SUMO-1, which is polar and positively charged, over that of SUMO-2, whose C-terminus is mainly hydrophobic (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006); and Shen et al., The Biochemical Journal 397:279-88 (2006)).
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 341.39, ALogP 4.39, HBA 5, HBD 2, PSA 105.11, QED 0.42
Compound (SMILES): CC(=O)N1c2cnc(NC(=O)O[C@@H](C)C(C)(C)C)nc2C2(CCC(F)(F)CC2)C1(C)C
InChIKey: BQJACMMFLPJGCR-ZDUSSCGKSA-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 = 259 nM (pChEMBL 6.590000152587891)
Descriptors: MW 438.52, ALogP 5.05, HBA 5, HBD 1, PSA 84.42, QED 0.7
Compound (SMILES): COC(=O)c1cc2c(cn1)[nH]c1ccc(NCc3ccccc3)cc12
InChIKey: JTYYMOMTGZSRFM-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P34903
Assay: Binding affinity to human recombinant GABAA alpha3 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 331.38, ALogP 4.11, HBA 4, HBD 2, PSA 67.01, QED 0.55
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)CC1
InChIKey: GYHRANYJOBNLHW-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma-2 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 447.96, ALogP 5, HBA 3, HBD 1, PSA 35.58, QED 0.7
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NCC(N)=O
InChIKey: YJKNBYBEJYUUHW-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1A (SINGLE PROTEIN), Homo sapiens
UniProt: P36894
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 15400 nM (pChEMBL 4.809999942779541)
Descriptors: MW 441.89, ALogP 4.02, HBA 5, HBD 3, PSA 110, QED 0.51
Compound (SMILES): C[C@]12CCC(=O)C=C1C(=O)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
InChIKey: PJMNEPMSGCRSRC-IEVKOWOJSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 279.9 nM (pChEMBL 6.550000190734863)
Descriptors: MW 300.4, ALogP 3.27, HBA 3, HBD 0, PSA 51.21, QED 0.69
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C(F)F)c2)n1
InChIKey: FRYSBKWOXOBQNB-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 448.45, ALogP 5.94, HBA 5, HBD 2, PSA 71.42, QED 0.34
Compound (SMILES): CC(C)Oc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: PPBVLCXRMSVIEI-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 68.3 nM (pChEMBL 7.170000076293945)
Descriptors: MW 475.52, ALogP 3.03, HBA 8, HBD 1, PSA 142.07, QED 0.51
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccc(Cl)cc3)cc2)nc2cnccc12)C(N)=O
InChIKey: KFUPSHPLPAHYAR-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 441.92, ALogP 5.16, HBA 5, HBD 2, PSA 104.69, QED 0.43
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: ATFCNLVUGGJYEX-DHRBKSIMSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant
Measurement: Ki = 75.5 nM (pChEMBL 7.119999885559082)
Descriptors: MW 701.8, ALogP -0.95, HBA 10, HBD 6, PSA 252.68, QED 0.09
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(Cl)c(O)c(C(N)=O)c3)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: FRJRUCNOMGJHID-AWEZNQCLSA-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 = 14.2 nM (pChEMBL 7.849999904632568)
Descriptors: MW 599.48, ALogP 2.69, HBA 10, HBD 3, PSA 151.61, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2ccc(O)cc2O3)c([N+](=O)[O-])c1
InChIKey: WYRAOTGCFPPQHI-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 4406.5 nM (pChEMBL 5.360000133514404)
Descriptors: MW 433.44, ALogP 1.95, HBA 8, HBD 2, PSA 153.07, QED 0.55
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1C/C=C1\CCC(CNC(=O)c2cc3ccccc3[nH]2)C1
InChIKey: HFPHPWOFSUNVRW-QIBJJAHESA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylscopolamine from human dopamine D3 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 459.59, ALogP 4.06, HBA 5, HBD 3, PSA 96.27, QED 0.48
Compound (SMILES): Cc1onc(-c2ccccc2)c1COCCCCCNC(=O)C(C)S
InChIKey: SXOJHTOVXGQVDN-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 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 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 362.5, ALogP 3.77, HBA 5, HBD 2, PSA 64.36, QED 0.5
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4cccc(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: WAYSVGLDKMEZLH-KRWDZBQOSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin)
Measurement: IC50 = 818 nM (pChEMBL 6.090000152587891)
Descriptors: MW 512.97, ALogP 4.89, HBA 7, HBD 1, PSA 85.81, QED 0.45
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCCN5CCCCCC5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: BHNAORVEXRBMID-YOGXEWEVSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from Sprague-Dawley rat brain membrane histamine H3 receptor assessed as inhibition constant incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 464.74, ALogP 6.65, HBA 3, HBD 0, PSA 15.71, QED 0.44
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) in presence of 25 uM ATP
Measurement: IC50 > 8000 nM (pChEMBL 5.0970001220703125)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@H](C)C2)c1
InChIKey: HVXGLCUTIOCPRK-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta 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 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): CC1=CC(C)=[N+]2C1=C(c1ccc(OCCn3cc(CCCOc4cc(C(=O)O)nc5c(C)c6nc(C(=O)O)cc(O)c6cc45)nn3)cc1)c1nc(C)cn1[B-]2(F)F
InChIKey: KHEPRHNLTBJKJD-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells using furimazine as substrate incubated for 30 mins in presence of zaprinast followed by substrate addition by BERT-based equilibrium binding assay
Measurement: Kd = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 776.57
Compound (SMILES): O=c1ccc2c(N3CCCN(CCCCOc4ccc5ccnn5c4)CC3)ccc(O)c2[nH]1
InChIKey: RGAXRFLOVCZZNS-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor assessed as beta arrestin-2 recruitment
Measurement: EC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 447.54, ALogP 3.25, HBA 7, HBD 2, PSA 86.1, QED 0.42
Compound (SMILES): CC(C)=CCN1CC[C@@]2(C)c3cc(O)ccc3C[C@H]1[C@H]2C
InChIKey: VOKSWYLNZZRQPF-MDASCCDHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR receptor assessed as inhibition constant by cheng-prusoff equation assay
Measurement: Ki = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 285.43, ALogP 3.88, HBA 2, HBD 1, PSA 23.47, QED 0.83
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCNCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: POIIDLJXIAHDFT-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 1002.76
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(Cl)c(OC)c4)nn32)CC1
InChIKey: BCPNJXKITYKKCV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 54.2 nM (pChEMBL 7.269999980926514)
Descriptors: MW 473.96, ALogP 3.1, HBA 7, HBD 2, PSA 111.71, QED 0.62
Compound (SMILES): O=C(Nc1ccc(-c2n[nH]c(=O)c3ccccc23)cc1)N1CCc2ccccc21
InChIKey: XTIYMUSBVIPTLM-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound. The inhibition data were fit using a curve-fitting program to determine the IC50; i.e., the concentration of compound required to inhibit 50% of kinase activity.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 382.42, ALogP 4.18, HBA 3, HBD 2, PSA 78.09, QED 0.55
Compound (SMILES): CCN(c1cc(-c2ccc(CN3CCN(C(=O)CCCCCCCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)CC3)cc2)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C)C1CCOCC1
InChIKey: AOIZISCRIVNZJJ-XWJFFXCMSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Induction of degradation of EZH2 degradation in human MDA-MB-453 cells
Measurement: EC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 1154.53
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCC3(CC2)CC(=O)c2ccc(OCCO)cc2O3)c([N+](=O)[O-])c1
InChIKey: KDHNWXMBKLGVCS-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 46.5 nM (pChEMBL 7.329999923706055)
Descriptors: MW 477.5, ALogP 1.62, HBA 9, HBD 2, PSA 162.3, QED 0.46
Compound (SMILES): CNC(=O)c1cc(COC(=O)c2ccc3c(c2)c(COc2ccc4[nH]ccc4c2)cn3S(C)(=O)=O)cc(=O)[nH]1
InChIKey: VJTGCTYUJTUPBS-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of human recombinant His6 tagged SENP1 catalytic domain expressed in Escherichia coli BL21 (DE3) using SUMO3-AMC as substrate incubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 44000 nM (pChEMBL 4.360000133514404)
Descriptors: MW 548.58, ALogP 2.91, HBA 8, HBD 3, PSA 152.35, QED 0.25
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)[C@@H](C)n2nnnc2N1C
InChIKey: BVMAEXVWFIGNKQ-SECBINFHSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 324.35, ALogP 1.47, HBA 7, HBD 2, PSA 104.62, QED 0.74
Compound (SMILES): COc1ccc(S(=O)(=O)N2CC(C)(C)C(CCSCc3ccccc3)C2C(=O)NO)cc1
InChIKey: APCLVQAXJIHPKK-UHFFFAOYSA-N
Target: Stromelysin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08254
Assay: Inhibition of human MMP3 using (7-methoxycoumarine-4-yl)-Arg-Pro-Lys-Pro-Tyr-Ala-Nva-Trp-Met-Lys(Dnp)-NH2 substrate by fluorimetric analysis
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 478.64, ALogP 3.54, HBA 6, HBD 2, PSA 95.94, QED 0.33
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: JGOIBENTSQHWDQ-UHFFFAOYSA-O
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 973.71, ALogP 14.06, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(C(F)(F)F)c1
InChIKey: WECCALUSSAUMLJ-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TrkA (unknown origin) in presence of ATP
Measurement: IC50 = 959 nM (pChEMBL 6.019999980926514)
Descriptors: MW 404.37, ALogP 3.9, HBA 5, HBD 2, PSA 71.42, QED 0.51