lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCn1cc(S(N)(=O)=O)c2cc(NC(=O)c3cc(-c4ccc(OC)c(OC)c4)nc4ccccc34)ccc21
InChIKey: WIOLBSANTGEQEV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 by stopped flow CO2 assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 530.61, ALogP 4.79, HBA 7, HBD 2, PSA 125.54, QED 0.31
Compound (SMILES): CCN(C)C(=O)Oc1ccc(C2CC(=O)c3c(OC(=O)N(C)CC)cc(OC(=O)N(C)CC)cc3O2)cc1
InChIKey: IIGQDHXPZZVVIP-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using butyrylthiocholine as substrate incubated for 15 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 24500 nM (pChEMBL 4.610000133514404)
Descriptors: MW 527.57, ALogP 4.74, HBA 8, HBD 0, PSA 114.92, QED 0.51
Compound (SMILES): Cn1c(-c2ccc(Cl)cc2)nc2cc(C(N)=O)ccc21
InChIKey: YVWCSKRSJPBFSA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant CA12 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: IC50 > 360 nM (pChEMBL 6.443999767303467)
Descriptors: MW 285.73, ALogP 2.99, HBA 3, HBD 1, PSA 60.91, QED 0.79
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(N/N=C/c3ccc(F)cc3)nc(Nc3ccccc3)n2)cc1
InChIKey: ZRKHVDWSWUQPKJ-AFUMVMLFSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 8.46 nM (pChEMBL 8.069999694824219)
Descriptors: MW 478.51, ALogP 3.59, HBA 9, HBD 4, PSA 147.28, QED 0.22
Compound (SMILES): NC(=O)c1ccc(OCC2CCC2)cc1
InChIKey: BFGNGDGWDOFCPT-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N3
Assay: Inhibition of human N-terminal 6His-tagged PARP15 (460 to 656 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 2398.83 nM (pChEMBL 5.619999885559082)
Descriptors: MW 205.26, ALogP 1.96, HBA 2, HBD 1, PSA 52.32, QED 0.82
Compound (SMILES): Cc1onc(-c2ccc(F)cc2)c1COc1ccc2c(n1)CCN(C(=O)CS(C)(=O)=O)C2
InChIKey: GTVLCHCOKLXHLY-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 459.5, ALogP 2.69, HBA 7, HBD 0, PSA 102.6, QED 0.56
Compound (SMILES): Cc1cc(NC(=O)NC(=O)Cc2ccc(F)cc2)ncc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: ZXAMVJNNDJRGFG-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal GST-tagged PDGFRbeta (unknown origin) (557 to 1106 residues) measured by spectrophotometric analysis
Measurement: IC50 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 460.47, ALogP 4.01, HBA 7, HBD 2, PSA 111.03, QED 0.45
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4ccc(Cl)cc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: VKBVKOURJLIITC-CPIJZORTSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human adenosine A3 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 131.83 nM (pChEMBL 6.880000114440918)
Descriptors: MW 461.91, ALogP 1.5, HBA 10, HBD 4, PSA 134.78, QED 0.43
Compound (SMILES): CNC(=O)C1CN(c2ncc(C(C)C)c3cc(Nc4ccnc(N5CC[C@@H](O)[C@@](C)(F)C5)n4)ncc23)C1
InChIKey: URIYZCBXTNEXJL-IBVKSMDESA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR in human A-431 cells preincubated for 4 to 5 hrs followed by EGF stimulation for 10 mins by AlphaLISA method
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 508.6, ALogP 2.77, HBA 9, HBD 3, PSA 119.4, QED 0.46
Compound (SMILES): O=C(CCCCc1nnc(-c2cc3c([nH]c4ccccc43)c(-c3ccc(C(F)(F)F)cc3)n2)o1)NO
InChIKey: QAXZYFCMHHCIBX-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 495.46, ALogP 5.67, HBA 6, HBD 3, PSA 116.93, QED 0.15
Compound (SMILES): COc1ccc(CN(C)CCCNC(=O)c2ccc3ccccc3n2)cc1OC
InChIKey: FAUQUDLQMVCUDE-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Binding affinity to DOR (unknown origin) assessed as inhibition constant by radioligand binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 393.49, ALogP 3.5, HBA 5, HBD 1, PSA 63.69, QED 0.56
Compound (SMILES): CC(=O)Nc1ccccc1OCc1cn(CCNC(=O)C(CC(C)C)C(=O)NO)nn1
InChIKey: OJABORXYWINGBT-UHFFFAOYSA-N
Target: Collagenase ColQ1 (SINGLE PROTEIN), Bacillus cereus
UniProt: B9J3S4
Assay: Inhibition of Bacillus cereus ATCC 14579 collagenase unit of ColQ1 assessed as inhibition constant incubated for 144 seconds by FRET based assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 432.48, ALogP 1.1, HBA 8, HBD 4, PSA 147.47, QED 0.24
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCC(=O)O)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O
InChIKey: FNXRMYXIFMHONZ-HUKDYVGWSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO cells coexpressing beta-arrestin-2 assessed as increase in beta arrestin-2 recruitment incubated for 1 hr by chemiluminescence based pathHunter assay
Measurement: EC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 4224.73
Compound (SMILES): CCN(CC)C(=O)c1ccc2c(c1)nc(Cc1ccc(OC(=O)N3CCC3)cc1)n2CCC(C)C
InChIKey: HTNKYLZCROSXPM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured every 30 sec for 3 mins by DTNB-based UV analysis
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 476.62, ALogP 5.36, HBA 5, HBD 0, PSA 67.67, QED 0.42
Compound (SMILES): CC(C)C[C@H](NC(=O)Cc1ccccc1)B(O)O
InChIKey: AFAPDUQLUWIMPW-LBPRGKRZSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome beta-5i subunit in human PBMC using Ac-ANW-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 249.12
Compound (SMILES): CCCCCC[Si](C)(C)c1cc(O)c2c(c1)OC(C)(C)[C@@H]1CC=C(CO)C[C@@H]21
InChIKey: SXFHTGCTQJDRTF-WOJBJXKFSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at recombinant human CB2 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin stimulation and measured after 15 mins by HTRF assay
Measurement: EC50 = 61.28 nM (pChEMBL 7.210000038146973)
Descriptors: MW 402.65
Compound (SMILES): N#Cc1ccc(C[C@H](NC(=O)Nc2ccc(F)cc2)C(=O)N2CCCc3ccccc32)cc1
InChIKey: RPCMTLXSDIBBNI-QHCPKHFHSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Antagonist activity at human FPR1 transfected in human HL-60 cells assessed as inhibition of fMLF-induced intracellular calcium mobilization preincubated for 10 mins followed by fMLF addition and measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 24200 nM (pChEMBL 4.619999885559082)
Descriptors: MW 442.49, ALogP 4.41, HBA 3, HBD 2, PSA 85.23, QED 0.61
Compound (SMILES): CCc1ccc(-c2nc3cc(NC(=O)c4cc([N+](=O)[O-])ccc4Br)ccc3o2)cc1
InChIKey: BJSIVXYQIGFUCG-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inverse agonist activity at GAL4-tagged human PPARgamma LBD expressed in CHO cells measured after 6 hrs by firefly luciferase reporter assay
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 466.29, ALogP 5.98, HBA 5, HBD 1, PSA 98.27, QED 0.29
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCC3)ccc12
InChIKey: MWPKIJXVHHDLCZ-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N3
Assay: Inhibition of human N-terminal 6His-tagged PARP15 (460 to 656 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 478.63 nM (pChEMBL 6.320000171661377)
Descriptors: MW 246.27, ALogP 1.4, HBA 3, HBD 2, PSA 74.95, QED 0.86
Compound (SMILES): O=C1NC(N2CCN(c3ccc(F)cc3)CC2)=N/C1=C\c1ccc2c(c1)OCCO2
InChIKey: HLOKDFAILZNLKF-AQTBWJFISA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Mus musculus
UniProt: O35491
Assay: Inhibition of mouse recombinant GST-fused CLK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 408.43, ALogP 2.25, HBA 6, HBD 1, PSA 66.4, QED 0.77
Compound (SMILES): COc1cc(Nc2ncc(C)c(Nc3ccc4oc(=O)[nH]c4c3)n2)cc(C)c1OC
InChIKey: TUBVOAQAKUPGHR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) in presence of NADPH
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 407.43, ALogP 4.03, HBA 8, HBD 3, PSA 114.3, QED 0.44
Compound (SMILES): CCCCCCCCCCCOc1cccc(CCC(=O)NC[C@@H](O)COP(=O)(O)OC[C@H](C)C(=O)O)c1
InChIKey: VEKWMEWDMAYZSN-LADGPHEKSA-N
Target: Probable G-protein coupled receptor 174 (SINGLE PROTEIN), Mus musculus
UniProt: Q3U507
Assay: Antagonist activity at mouse GPR174 transfected in human HEK293FT cells co-transfected with AP-TGFalpha assessed as inhibition of LysoPalloT-NH-C3-ph-m-O-C11-induced AP-TGFalpha release incubated for 90 mins by TGFalpha shedding assay
Measurement: IC50 = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 559.64, ALogP 4.86, HBA 7, HBD 4, PSA 151.62, QED 0.11
Compound (SMILES): Cc1ccc(Nc2cc(-c3ccnc(-n4ncc5cc(C(C)(C)C)cc(F)c5c4=O)c3CO)cn(C)c2=O)nc1
InChIKey: DHPUYPJPYZUNAH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK C481R mutant (unknown origin) expressed in baculovirus infected Trichoplusia ni pro cells incubated for 30 mins in presence of ATP by Microfluidic chip based mobility shift assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 540.6, ALogP 4.52, HBA 9, HBD 2, PSA 114.93, QED 0.34
Compound (SMILES): O=C(COCN1CCCCC1)CN1Nc2cc(O)ccc2-c2c1c1ccc(O)cc1oc2=O
InChIKey: ZOIOYCAFYGHCOY-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Antagonist activity at progesterone receptor in human MCF7 cells
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 451.48, ALogP 3.05, HBA 9, HBD 3, PSA 115.48, QED 0.49
Compound (SMILES): Cc1cc(-c2n[nH]c3ccc(Nc4ccccc4C#N)cc23)ccn1
InChIKey: YILNWNTWLAQENW-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of pcDNA5FRT-TO-GFP fused - LRRK2 G2019S mutant (unknown origin) transfected in HEK293 cells incubated for 24 hrs by ELISA
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 325.38, ALogP 4.55, HBA 4, HBD 2, PSA 77.39, QED 0.58
Compound (SMILES): C[C@@H](c1cn(-c2ccc(Cl)cc2F)nn1)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
InChIKey: MJTYFRXZEQXMIA-FKIZINRSSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using mephenytoin as substrate in presence of NADPH
Measurement: IC50 = 10300 nM (pChEMBL 4.989999771118164)
Descriptors: MW 448.84, ALogP 3.62, HBA 7, HBD 1, PSA 81.65, QED 0.49
Compound (SMILES): Cl.Clc1ccc2[nH]c3c(c2c1)CCNC3C(c1ccccc1)c1ccccc1
InChIKey: MLTGINFZLSSFDX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 0.3236 nM (pChEMBL 9.489999771118164)
Descriptors: MW 372.9, ALogP 5.84, HBA 1, HBD 2, PSA 27.82, QED 0.46
Compound (SMILES): COc1ccccc1N1CCN(CCCCCNc2nc(N)nc(N)n2)CC1
InChIKey: QWZAQKYTKIEATF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in HEK293 cells incubated for 1 hr by microbeta plate reader analysis
Measurement: Ki = 947 nM (pChEMBL 6.019999980926514)
Descriptors: MW 386.5, ALogP 1.45, HBA 9, HBD 3, PSA 118.45, QED 0.55
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4cccc(OC)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: RTDGLSRULFVAFC-FUWISXPPSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human adenosine A2B receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 498.54, ALogP 1, HBA 11, HBD 4, PSA 152.88, QED 0.35
Compound (SMILES): COc1cc(C(=O)Nc2cc(OC(F)(F)F)ccc2-n2cncn2)ccc1OC1CCC1
InChIKey: IQAAAODLPLVLBB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 448.4, ALogP 4.36, HBA 7, HBD 1, PSA 87.5, QED 0.58
Compound (SMILES): CC(O)COC(=O)c1csc(Nc2ccc(S(N)(=O)=O)cc2)n1
InChIKey: OQSFYLORJNENFQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 84.4 nM (pChEMBL 7.070000171661377)
Descriptors: MW 357.41, ALogP 1.07, HBA 8, HBD 3, PSA 131.61, QED 0.66
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CSCc2cccc(c2)CSC(C)(C)[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: IXQMIHWLSWEYPU-SIXPOYHZSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]NDP-alpha-MSH from human MC4R expressed in HEK293 cells by competitive binding assay
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 1135.43
Compound (SMILES): CNC(=O)c1cc(C)cc(-c2cnc3cc(-c4cnn(C(C)C)c4)c(O[C@H]4CCOC4)nn23)c1
InChIKey: QJSDPLBJLHJTJP-FQEVSTJZSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human FGFR3 V555M mutant using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 460.54, ALogP 3.68, HBA 8, HBD 1, PSA 95.57, QED 0.47
Compound (SMILES): CC(C)c1n[nH]c2c(NCc3ccc(-c4cnccn4)cc3)nc(SCCN)nc12
InChIKey: ORQQCLLJNPKLIL-UHFFFAOYSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of GST-tagged human CDK12/Cyclin K expressed in Sf9 cells using RBER-IRStide peptide as substrate in presence of ATP and [gamma33-P] ATP by radioisotope filter binding assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 420.55, ALogP 3.6, HBA 8, HBD 3, PSA 118.29, QED 0.29
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nn(-c2cccnc2)c2cc(Cl)ccc12
InChIKey: VGSSLTPCGYPSOR-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by ADP-Glo assay
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 405.85, ALogP 3.07, HBA 9, HBD 3, PSA 144.35, QED 0.47
Compound (SMILES): Nc1ccc(C#CCN(C(=O)Cc2ncc(C(F)(F)F)cc2C(F)(F)F)c2ccc(F)cc2)nn1
InChIKey: LHFFKHVGAKIDNO-UHFFFAOYSA-N
Target: DNA polymerase subunit gamma-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54098
Assay: Inhibition of human DNA polymerase gamma
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 497.37, ALogP 4.26, HBA 5, HBD 1, PSA 85, QED 0.43
Compound (SMILES): COc1ccc(CN2CCC[C@H](OCc3ccc(C)cc3)C2)cc1F
InChIKey: DGDPBRUTRCRWFD-IBGZPJMESA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 5.495 nM (pChEMBL 8.260000228881836)
Descriptors: MW 343.44, ALogP 4.32, HBA 3, HBD 0, PSA 21.7, QED 0.78
Compound (SMILES): CN(C)c1ccc(C(=O)N(CC(=O)NCc2ccccc2)Cc2ccc(C(=O)NO)cc2F)cc1
InChIKey: GBIQEYYBFBGNOZ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal FLAG-tagged HDAC2 (1 to 488 residues) expressed in Sf9 insect cells using Z-Lys(Ac)-AMC as fluorogenic substrate incubated for 90 mins by microplate reader analysis
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 478.52, ALogP 2.97, HBA 5, HBD 3, PSA 101.98, QED 0.32
Compound (SMILES): C#CCNC1CCc2ccccc2C1
InChIKey: RELIUPLDFYVMJL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Time dependent inhibition of human recombinant MAOB at 0.25 to 1.25 uM using kynuramine substrate by fluorescence spectrophotometry based graphing of slopes of Lineweaver-Burk plots versus inhibitor concentration
Measurement: Ki = 435 nM (pChEMBL 6.360000133514404)
Descriptors: MW 185.27, ALogP 1.77, HBA 1, HBD 1, PSA 12.03, QED 0.69
Compound (SMILES): CCOc1ncc(-c2nc(C(F)(F)F)sc2N2CCN(C(=O)Cn3ccc(C(F)(F)F)n3)[C@H](C)C2)cn1
InChIKey: QSPYPBJJEIJUBY-GFCCVEGCSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Q patch-clamp method
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 549.5, ALogP 3.97, HBA 9, HBD 0, PSA 89.27, QED 0.43
Compound (SMILES): COc1cccc(CO[C@@H]2CCC[C@H]2Nc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1
InChIKey: DKXQAUQBUSRNHS-PAXAQNQPSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 281.84 nM (pChEMBL 6.550000190734863)
Descriptors: MW 471.51, ALogP 1, HBA 11, HBD 4, PSA 144.01, QED 0.38
Compound (SMILES): COc1cc(Nc2nc(C#N)cc3cn[nH]c23)cc(OC)c1OC
InChIKey: BKEVNHGVRXQWRJ-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Antagonist activity at wild type A1R (unknown origin) expressed in CHO-K1 cells assessed as inhibition of NECA reduced forskolin stimulated cAMP accumulation incubated for 30 mins
Measurement: IC50 = 10.23 nM (pChEMBL 7.989999771118164)
Descriptors: MW 325.33, ALogP 2.6, HBA 7, HBD 2, PSA 105.08, QED 0.74
Compound (SMILES): O=C(Nc1nc2cccc([C@H]3CC[C@@H](NC(=O)[C@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: JQKDWSJGLLIFBM-KWCYVHTRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 455 nM (pChEMBL 6.340000152587891)
Descriptors: MW 403.43, ALogP 2.88, HBA 5, HBD 2, PSA 88.39, QED 0.8
Compound (SMILES): C[C@@H]1CC(=O)Nc2ncnc(N3CCN(C(=O)[C@H](CN)c4ccc(Cl)cc4)[C@@H]4C[C@@H]43)c21
InChIKey: ODXLOWHHBMQSMU-VDNDLQMASA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Inhibition of recombinant AKT2 (120 to 481 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 440.94, ALogP 2.11, HBA 6, HBD 2, PSA 104.45, QED 0.75
Compound (SMILES): N#Cc1ccc(C[C@H](NC(=O)Nc2ccc(F)cc2)C(=O)N2CCCCC2)cc1
InChIKey: LUSNDONHBJYYRL-FQEVSTJZSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Antagonist activity at human FPR1 transfected in human HL-60 cells assessed as inhibition of fMLF-induced intracellular calcium mobilization preincubated for 10 mins followed by fMLF addition and measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 20600 nM (pChEMBL 4.690000057220459)
Descriptors: MW 394.45, ALogP 3.44, HBA 3, HBD 2, PSA 85.23, QED 0.81
Compound (SMILES): CC#CC(=O)N1CCC[C@H]1n1nc(-c2ccc(C(=O)Nc3ccccn3)cc2)c2c(N)ncnc21
InChIKey: CVBABGVEYUMHNU-LJQANCHMSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Inhibition of TXK (unknown origin)
Measurement: IC50 = 368 nM (pChEMBL 6.429999828338623)
Descriptors: MW 466.51, ALogP 2.87, HBA 8, HBD 2, PSA 131.92, QED 0.44
Compound (SMILES): Cl.Oc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1O
InChIKey: OHFKUXRZGXUUES-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 85.11 nM (pChEMBL 7.070000171661377)
Descriptors: MW 280.33, ALogP 2.81, HBA 3, HBD 4, PSA 68.28, QED 0.55
Compound (SMILES): O=Cc1ccc(-c2ccccc2OCF)cc1
InChIKey: VWXWDHIJTXVFHJ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Competitive binding affinity to human D3R in transfected cells
Measurement: Ki = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 230.24, ALogP 3.47, HBA 2, HBD 0, PSA 26.3, QED 0.75
Compound (SMILES): CN1CCN(c2cnn3ccc(N4CCC[C@@H]4c4cc(F)ccc4F)nc23)C1=O
InChIKey: LNCLNCFOGMZULV-MRXNPFEDSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA G623R mutant (unknown origin) using TK-sub biotin peptide substrate preincubated for 30 mins followed by substrate addition and measured after 40 mins by FRET assay
Measurement: IC50 = 34.7 nM (pChEMBL 7.460000038146973)
Descriptors: MW 398.42, ALogP 3.22, HBA 5, HBD 0, PSA 56.98, QED 0.68
Compound (SMILES): Cc1cccc(C(=O)N2CCC3(CCNCC3)CC2)c1
InChIKey: FRKWUXZCSLOPIC-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-4/beta-1/delta (PROTEIN COMPLEX), Homo sapiens
UniProt: O14764
Assay: Antagonist activity at human alpha4beta1delta GABAA receptor expressed in HEK293 Flp-In cells by FMP assay
Measurement: IC50 = 181.97 nM (pChEMBL 6.739999771118164)
Descriptors: MW 272.39, ALogP 2.6, HBA 2, HBD 1, PSA 32.34, QED 0.85
Compound (SMILES): CC(C)n1c(-c2ccncc2)cc2c1CCNC2=O
InChIKey: MUKIIGVLQHTSFA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16512
Assay: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay
Measurement: IC50 = 1840 nM (pChEMBL 5.739999771118164)
Descriptors: MW 255.32, ALogP 2.42, HBA 3, HBD 1, PSA 46.92, QED 0.9
Compound (SMILES): C=CC[C@H](C(=O)NO)C(CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NC
InChIKey: GKHRDWHFKKUYAX-RGBJRUIASA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of MMP-2 (unknown origin)
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 389.5, ALogP 1.82, HBA 4, HBD 4, PSA 107.53, QED 0.26
Compound (SMILES): Cn1c(-c2ccc(Cl)cc2)nc2cc(B(O)O)ccc21
InChIKey: WMWYVVZMOOUZBP-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant CA12 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: IC50 > 360 nM (pChEMBL 6.443999767303467)
Descriptors: MW 286.53
Compound (SMILES): Fc1cc(COC2CCN(Cc3ccc4[nH]cnc4c3)CC2)ccc1Cl
InChIKey: DGIHILWHEUNSHI-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 8.318 nM (pChEMBL 8.079999923706055)
Descriptors: MW 373.86, ALogP 4.54, HBA 3, HBD 1, PSA 41.15, QED 0.71
Compound (SMILES): Nc1ccc(-c2c(C(=O)c3ccc(OCCN4CC(C(=O)O)=CCC4=O)cc3)c3ccc(O)cc3oc2=O)cc1
InChIKey: FNTLYEBGPROJEG-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Antagonist activity at progesterone receptor in human MCF7 cells
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 540.53, ALogP 3.6, HBA 8, HBD 3, PSA 160.37, QED 0.17
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CCN(C(=O)[C@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: DVLBRDUTBJVBQN-RPYGNYITSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 692 nM (pChEMBL 6.159999847412109)
Descriptors: MW 443.5, ALogP 3.61, HBA 5, HBD 1, PSA 79.6, QED 0.78
Compound (SMILES): CCCn1c(=O)c2[nH]c(-c3ccc(OCC(=O)NCCNC(=O)CCNC(=O)CCCCNC(=O)CCCCCNC(=O)COc4ccc(/C=C/C5=[N+]6C(=Cc7ccc(-c8cccs8)n7[B-]6(F)F)C=C5)cc4)cc3)nc2n(CCC)c1=O
InChIKey: LYAYADHVKSFZEM-XMHGGMMESA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding affinity to A1R E172 5.30A mutant (unknown origin) by saturation NanoBRET binding assay
Measurement: Kd = 116.04 nM (pChEMBL 6.929999828338623)
Descriptors: MW 1144.12
Compound (SMILES): CSC1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1
InChIKey: HFLXYSRIPKXGOQ-YWEYNIOJSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Mus musculus
UniProt: O35491
Assay: Inhibition of mouse recombinant GST-fused CLK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 262.29, ALogP 1.6, HBA 5, HBD 1, PSA 59.92, QED 0.78
Compound (SMILES): CC(C)n1c(C(C)(C)O)nc2c(F)cc(-c3nc(N[C@@H]4CCOC[C@H]4O)ncc3Cl)cc21
InChIKey: QYJLBHRAPDJOSO-NVXWUHKLSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Biological Assay: CDK6/Cyclin D3: The purpose of the CDK6/Cyclin D3 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D3 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:1). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (±inhibitor), 2% glycerol, 10 mM MgCl2, 1 mM DTT, 3.5 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 4 nM (active sites) activated CDK6/Cyclin D3 in 40 mM HEPES buffer at pH 7.5.
Measurement: Ki = 13.9 nM (pChEMBL 7.860000133514404)
Descriptors: MW 463.94, ALogP 3.66, HBA 8, HBD 3, PSA 105.32, QED 0.53
Compound (SMILES): CCCCCNC(=O)/N=C(/N)NCCCc1nnc(C)s1.O=C(O)C(F)(F)F
InChIKey: MKSDFMBRUJQIOF-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 312.44, ALogP 1.58, HBA 4, HBD 3, PSA 105.29, QED 0.38
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(Cl)c2)ccn1
InChIKey: KPYMRFGAAXFXIK-FQEVSTJZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 391.9, ALogP 4.72, HBA 5, HBD 2, PSA 86.47, QED 0.71
Compound (SMILES): CC[C@@H]1CN2CC[C@]3(O)c4c(cccc4OC)N[C@@H]3[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: QXFXDJATKPXTFF-LIMHOZKTSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Agonist activity at recombinant rat DOP stably expressed in CHO-K1 cell membrane assessed as [35S]GTPgammaS binding
Measurement: EC50 = 1492 nM (pChEMBL 5.829999923706055)
Descriptors: MW 416.52, ALogP 2.5, HBA 7, HBD 2, PSA 80.26, QED 0.43
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1-n1cnc2cnc(Nc3ccc(C#N)cc3)nc21
InChIKey: GBIZDABECURRFX-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase Y181C mutant assessed as reduction in luciferase reporter activity by single-round assay
Measurement: EC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 391.44, ALogP 4.58, HBA 7, HBD 1, PSA 103.21, QED 0.51
Compound (SMILES): Clc1ncc(Cl)c(-n2ccc3ncccc32)n1
InChIKey: KBGCWMXCIHNWOI-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: O75582
Assay: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 3 hrs followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 265.1, ALogP 3.12, HBA 4, HBD 0, PSA 43.6, QED 0.63
Compound (SMILES): CCc1cc(=O)[nH]c(-n2nc(C)cc2NC(=O)c2ccccc2F)n1
InChIKey: ZMIPRHNWOMKZFW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Antagonist activity at 5-HT2B receptor (unknown origin) transfected in HEK293 cells assessed as beta-arrestin translocation by Tango assay
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 341.35, ALogP 2.22, HBA 5, HBD 2, PSA 92.67, QED 0.76
Compound (SMILES): COc1cc(N2CCC(N3CCN(CCO)CC3)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: KRXROXSPQRVKGS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibitory Ability Assay: The composition of the assay buffer used in the activity measurement was 50 mM Tris-HCl pH 7.5, 100 mM NaCl, 7.5 mM MgCl2, 3 mM KCl, 0.01% Tween 20, 0.1% BSA, 1 mM DTT. The enzymatic reaction was carried out hereto by using the peptide substrate labeled with ATP of 50 mM concentration and biotin of 0.5 mM concentration. The analysis of an EGFR activity inhibitory effect of the compound was carried out in accordance with the analysis reaction recipe below.Component 1: 4 ml of EGFR wild-type or mutation enzymeComponent 2: 2 ml of compound solutionComponent 3: 4 ml of peptide labeled with ATP and biotinThe enzymatic reaction was initiated by mixing Component 1 and Component 2 first, and then, adding component 3. After the reaction for 2 hours at 37° C., 10 ml of a measurement solution consisting of streptavidin-XL665 provided by Cisbio and anti-phosphotyrosine antibody labeled with europium was added to the enzymatic reaction solution and reacted for 1 hour at ambient temperature. Finally, the ratio of fluorescence values at 615 nm and 665 nm was obtained by using the Envision equipment of Perkin-Elmer, and the enzymatic activity was quantitatively measured, and the inhibitory ability of the compound was confirmed. The measurement values measured at the seven concentrations of the compound were analyzed by using the Prism program (version 5.01, Graphpad Software, Inc.), and IC50 value of the compound was calculated, which is an inhibitory ability indicator.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 631.2, ALogP 3.58, HBA 11, HBD 4, PSA 135.19, QED 0.25
Compound (SMILES): Cn1ccnc1-c1ccc2c(c1)CCN(S(=O)(=O)c1ccc3c(c1)CCO3)C2
InChIKey: LBPFUDXLAJFMBK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human muscarinic M1 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by by Fluo-4AM staining based fluorescence assay
Measurement: IC50 = 1318.26 nM (pChEMBL 5.880000114440918)
Descriptors: MW 395.48, ALogP 2.77, HBA 5, HBD 0, PSA 64.43, QED 0.68
Compound (SMILES): CCSC1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1C
InChIKey: NZMFVJNZGKELJC-POHAHGRESA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Mus musculus
UniProt: O35491
Assay: Inhibition of mouse recombinant GST-fused CLK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 290.34, ALogP 2.34, HBA 5, HBD 0, PSA 51.13, QED 0.78
Compound (SMILES): CCc1cc2ncc(CN3CCN(c4cc5cccc(C(=O)NC)c5cn4)CC3)cc2[nH]c1=O
InChIKey: RLWLFXINNNSDCN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of PARP-2 (unknown origin) binding to DNA assessed as DNA trapping activity
Measurement: IC50 = 2976 nM (pChEMBL 5.53000020980835)
Descriptors: MW 456.55, ALogP 2.72, HBA 6, HBD 2, PSA 94.22, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(N/C=C/C(=O)c2ccc([N+](=O)[O-])cc2)cc1
InChIKey: XOYJWBOEURENBY-MDZDMXLPSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to human CA4 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 347.35, ALogP 2.05, HBA 6, HBD 2, PSA 132.4, QED 0.36
Compound (SMILES): CCCNNC(=O)c1ccc(NC(=O)Cc2ccccc2)cc1
InChIKey: NWOAWPYSTZJWRK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using fluorescent as substrate measured for 10 mins by fluorescence based microtiter plate assay
Measurement: IC50 = 2991 nM (pChEMBL 5.519999980926514)
Descriptors: MW 311.38, ALogP 2.51, HBA 3, HBD 3, PSA 70.23, QED 0.54
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CS/C(C(=O)O)=C(/C(N)=O)SC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: PNUQGRIALHGKEH-DYYKIGPLSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Agonist activity at human MC1R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: EC50 = 0.4786 nM (pChEMBL 9.319999694824219)
Descriptors: MW 2168.47
Compound (SMILES): O=C(NO)c1ccc(Cn2sc3ccccc3c2=O)cc1
InChIKey: ZBKIYZUDBOQUME-UHFFFAOYSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of recombinant HDAC10 (unknown origin) using RHKKAc-AMC fluorogenic substrate by microtiter plate reader assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 300.34, ALogP 2.23, HBA 5, HBD 2, PSA 71.33, QED 0.58
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CSc3nnc(c4c3CCC3C(CC4)C3COC(=O)NCCOCCOCCN)SC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: YXIBEMYOGWJEQC-HSTSIONXSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: EC50 = 1.122 nM (pChEMBL 8.949999809265137)
Descriptors: MW 2431.85
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(N)c(C(=O)c4c(Cl)cccc4Cl)s3)cn2)CC1
InChIKey: JWYHKDMZXSHNLA-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant full length His-tagged CDK9/Cyclin T1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 463.39, ALogP 4.15, HBA 8, HBD 2, PSA 87.38, QED 0.55
Compound (SMILES): CN(C(=O)Cc1ccccc1)[C@@H]1C[C@]23CCN(CC4CC4)[C@H](Cc4ccc(O)cc42)[C@]32CC[C@@H]1O2
InChIKey: KCDPGHGVBKHDSF-MMAVNDQVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 2 hrs by scintillation counting method
Measurement: EC50 = 43.6 nM (pChEMBL 7.360000133514404)
Descriptors: MW 472.63, ALogP 4.06, HBA 4, HBD 1, PSA 53.01, QED 0.71
Compound (SMILES): Cc1ccc2c(=O)[nH]c(CSc3ncccn3)nc2c1C
InChIKey: NHFMMPLQVIZDPX-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of PARP2 (unknown origin)
Measurement: IC50 = 17400 nM (pChEMBL 4.760000228881836)
Descriptors: MW 298.37, ALogP 2.62, HBA 5, HBD 1, PSA 71.53, QED 0.59
Compound (SMILES): Cc1ccc(C2NCCc3c2[nH]c2ccc(F)cc32)c(C)c1.Cl
InChIKey: NAUNESXVOQEWDK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 537 nM (pChEMBL 6.269999980926514)
Descriptors: MW 294.37, ALogP 4.16, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): Cn1nc(NC(=O)c2ccccc2)c2cc(Nc3ccccc3)ncc21
InChIKey: YLOYXGAZLBJFMU-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding affinity to wild type A1R (unknown origin) expressed in CHO-K1 cells assessed as equilibrium binding affinity constant by nanoBRET assay
Measurement: Ki > 954.99 nM (pChEMBL 6.019999980926514)
Descriptors: MW 343.39, ALogP 3.96, HBA 5, HBD 2, PSA 71.84, QED 0.59
Compound (SMILES): COC(=O)c1ccc2c(c1)C(=O)N(c1ccc(S(N)(=O)=O)cc1)C2=O
InChIKey: OWABLTCENMSAGE-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human recombinant CA9 assessed as inhibition constant incubated for 10 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 360.35, ALogP 0.92, HBA 6, HBD 1, PSA 123.84, QED 0.64
Compound (SMILES): NC(=O)[C@@H](Nc1ccc2c(c1)OCCn1cc(N3C(=O)OC[C@H]3CF)nc1-2)C1CC1
InChIKey: QTTBCYFVRARNAY-DYVFJYSZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Inhibition Assay: The biochemical inhibition of four PI3K isoforms by the Formula I compounds of Table 1. In addition, two clinically tested PI3K compounds, taselisib and pictilisib are included as comparators. The representative compounds of the invention exhibit strong activity against PI3Kα, and exhibit significantly enhanced selectivity relative to the other isoforms PI3Kβ, PI3Kδ, and PI3Kγ when compared to taselisib (GDC-0032) and pictilisib (GDC-0941). In particular, the selectivity ratios in the second from the right column of Table 2A show that each Formula I compounds 101-107 has a PI3K alpha to delta selectivity ratio far higher than taselisib or pictilisib. In fact, both taselisib and pictilisib have stronger activity against PI3K delta than against PI3K alpha, i.e. their selectivity ratios are less than 1. The selectivity ratios of Formula I compound 101-107 range from 301-fold to 634-fold.
Measurement: Ki = 0.051 nM (pChEMBL 10.289999961853027)
Descriptors: MW 415.43, ALogP 1.91, HBA 7, HBD 2, PSA 111.71, QED 0.75
Compound (SMILES): O=C(O)[C@H](CCc1ccccc1)NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
InChIKey: MRCMNWQMINJPCR-HNNXBMFYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of human recombinant MMP-8 (Phe21 to Gly467 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 421.82, ALogP 3.72, HBA 3, HBD 2, PSA 83.47, QED 0.71
Compound (SMILES): CC1(C)c2cc(OCCN3CCOCC3)ccc2C(=O)c2c1oc1cc(C#Cc3cc(OCC4CC4)ccn3)ccc21
InChIKey: HFDYFIJWKPLZKI-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of Src (unknown origin)
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 562.67, ALogP 5.6, HBA 7, HBD 0, PSA 74.03, QED 0.27
Compound (SMILES): COC(=O)N1C[C@@H](C)N(c2ncc3[nH]nc(-c4ccc(N5CCN(C)CC5)nc4)c3n2)[C@@H](C)C1
InChIKey: SCHRCCHASZMVAB-IYBDPMFKSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
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 465.56, ALogP 1.83, HBA 9, HBD 1, PSA 106.61, QED 0.62
Compound (SMILES): CCc1cc(-c2[nH]c3ccc(C4CCNCC4)cc3c2C(C)C)cc(C)n1
InChIKey: MSTNVPCHDVLSIT-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Inhibition Reporter Assay: HEK-Blue-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9 receptors were used for screening inhibitors of these receptors using an inducible SEAP (secreted embryonic alkaline phosphatase) reporter gene under the control of the IFN-β minimal promoter fused to five NF-κB and AP-1-binding sites. Briefly, cells are seeded into Greiner 384 well plates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 for TLR9) and then treated with test compounds in DMSO to yield a final dose response concentration range of 0.05 nM-50 μM. After a 30 minute compound pre-treatment at room temperature, the cells are then stimulated with a TLR7 ligand (gardiquimod at a final concentration of 7.5 μM), TLR8 ligand (R848 at a final concentration of 15.9 μM) or TLR9 ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB and AP-1 which induce the production of SEAP. After a 22 hour incubation at 37° C., 5% CO2, SEAP levels are determined with the addition of HEK-Blue Detection reagent (Invivogen), a cell culture medium that allows for detection of SEAP, according to manufacturer's specifications.
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 361.53, ALogP 5.69, HBA 2, HBD 2, PSA 40.71, QED 0.63
Compound (SMILES): Oc1ccc(C2CCC3(CC2)CC(O)C3)cc1
InChIKey: UOGJPRBLNZEFEU-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at human native full length ERalpha by cell-based transcriptional activation assay
Measurement: EC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 232.32, ALogP 3.19, HBA 2, HBD 2, PSA 40.46, QED 0.78
Compound (SMILES): C[C@H](N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@H]5CC[C@@](C)(O)CC5)c4n3)cc(NS(C)(=O)=O)c2C1=O)C(F)(F)F
InChIKey: CCGUJYVWXLUTIA-ADHMFCJJSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 609.63, ALogP 2.68, HBA 9, HBD 4, PSA 172.02, QED 0.33
Compound (SMILES): CN1CCN(C(=O)COc2ccc3cc(Oc4ccccn4)ccc3n2)CC1
InChIKey: CARGOCFGMJOVLC-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.8 by FRET based membrane potential assay
Measurement: IC50 = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 378.43, ALogP 2.57, HBA 6, HBD 0, PSA 67.79, QED 0.68
Compound (SMILES): NC(=O)c1ccc(OCc2cccc(Br)c2)cc1F
InChIKey: WBKKGOVCGYZDCH-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human PARP2 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 324.15, ALogP 3.27, HBA 2, HBD 1, PSA 52.32, QED 0.94