lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1(C)CN(C(=O)[C@@H](Cc2ccc(C#N)cc2)NC(=O)Nc2ccc(F)cc2)c2ccccc21
InChIKey: HYUWZRSPJCQRMB-HSZRJFAPSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Antagonist activity at human FPR2 transfected in human HL-60 cells assessed as inhibition of WKYMVM-induced intracellular calcium mobilization preincubated for 10 mins followed by WKYMVM addition measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 16400 nM (pChEMBL 4.789999961853027)
Descriptors: MW 456.52, ALogP 4.75, HBA 3, HBD 2, PSA 85.23, QED 0.58
Compound (SMILES): CCN(CC)CC(=O)Nc1n[nH]c2cc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)ccc12
InChIKey: FYGLIPNJRSHMFG-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin) incubated for 1 hr and measured by mobility shift assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 571.11, ALogP 4.96, HBA 9, HBD 4, PSA 145, QED 0.2
Compound (SMILES): N#Cc1cc2c(-c3ccccc3)n[nH]c2c(Nc2ccccc2)n1
InChIKey: JZZUNCXKCLNTHB-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity to wild type A3R (unknown origin) expressed in CHO-K1 cells assessed as equilibrium binding affinity constant by nanoBRET assay
Measurement: Ki = 43.65 nM (pChEMBL 7.360000133514404)
Descriptors: MW 311.35, ALogP 4.24, HBA 4, HBD 2, PSA 77.39, QED 0.59
Compound (SMILES): N#Cc1ccc(CSc2c[nH]c(=O)c(=O)[nH]2)cc1
InChIKey: DSUIXIWGKYSFSL-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Mus musculus
UniProt: P18894
Assay: Inhibition of full length mouse DAO transfected with CHO-K1 cells incubated for 30 mins by Amplex red and horseradish peroxidase based fluorescence assay
Measurement: EC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 259.29, ALogP 1.23, HBA 4, HBD 2, PSA 89.51, QED 0.64
Compound (SMILES): CC1(C)c2cc(OCCN3C4CCC3COC4)ccc2C(=O)c2c1oc1cc(C#Cc3cc(OCC4CC4)ccn3)ccc21
InChIKey: UHJMMAFUNGKSLA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 588.7, ALogP 6.13, HBA 7, HBD 0, PSA 74.03, QED 0.24
Compound (SMILES): O=C1CSc2cc(O)ccc2N1
InChIKey: GJRKJMSYGXBCNU-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Sus scrofa
UniProt: P00371
Assay: Inhibition of porcine kidney DAAO using D-serine as substrate assessed as H2O2 formation by amplex red and peroxidase-coupled continuous fluorescence spectrophotometric analysis
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 181.22, ALogP 1.44, HBA 3, HBD 2, PSA 49.33, QED 0.6
Compound (SMILES): COC(=O)C1CN(Cc2ccc(-n3cc(-c4ccc(Br)cc4)nn3)cc2)C1
InChIKey: DLWXDSIENBRWML-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.3, ALogP 3.3, HBA 6, HBD 0, PSA 60.25, QED 0.59
Compound (SMILES): O=C(O)Cc1ccc(Cl)c(OCCC2CCN(c3nc4ccc(Cl)cc4s3)CC2)c1
InChIKey: FUEGDUVTXZWBMT-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Transactivation of Gal4-fused human PPARdelta expressed in CHO cells co expressing pG5-Luc reporter
Measurement: EC50 = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 465.4, ALogP 5.92, HBA 5, HBD 1, PSA 62.66, QED 0.47
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCCc4ccc(OC)c(OC)c4)nc(C#Cc4ccc(Cl)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: WUZJMSWYANTMGC-XVOCEWIJSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 609.11, ALogP 2.64, HBA 11, HBD 4, PSA 143.65, QED 0.22
Compound (SMILES): C#CCN(Cc1ccc(F)cc1)c1cc(C)c(NC(=O)OC)c(C)c1
InChIKey: HXUBJZRAVCPBRH-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Time dependent inhibition of human liver microsome CYP2D6 preincubated for 0.5 hrs in presence or absence of NADPH followed by substrate addition by LC-MS/MS method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 340.4, ALogP 4.26, HBA 3, HBD 1, PSA 41.57, QED 0.83
Compound (SMILES): CCc1c(-c2ccnc(C)c2)[nH]c2ccc(C3CCNCC3)c(C)c12
InChIKey: IPIPJCBHPFVOGC-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
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 = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 333.48, ALogP 4.88, HBA 2, HBD 2, PSA 40.71, QED 0.72
Compound (SMILES): Cl.Fc1ccc2[nH]c3c(c2c1)CCNC3C1CCCCC1
InChIKey: FEQYATYCMOJBPU-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 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 272.37, ALogP 4.07, HBA 1, HBD 2, PSA 27.82, QED 0.8
Compound (SMILES): COc1ccc(-c2cccc(S(=O)(=O)N[C@@H](Cc3cccc(C(=N)N)c3)C(=O)N3CCN(C(=O)C(C)(C)C)CC3)c2)c(OC)c1
InChIKey: PQZAIIPXTKASNQ-NDEPHWFRSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Binding affinity to FXa (unknown origin) using Mes-DArg-Pro-Arg-AMC as substrate
Measurement: Ki = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 635.79, ALogP 3.26, HBA 7, HBD 3, PSA 155.12, QED 0.23
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCNC(=O)c2ccc(-c3ccc(N4CCN(C)CC4)c(NC(=O)c4c[nH]c(=O)cc4C(F)(F)F)c3)cc2)C(C)(C)C)cc1
InChIKey: BXKFHYMDHAHJSX-UOHLUGTHSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Displacement of N-(4'-((17-(5,5-difluoro-7-(1H-pyrrol-2-yl)-5H-5l4,6l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-3-yl)-15-oxo-4,7,10-trioxa-14-azaheptadecyl)carbamoyl)-4-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-3-yl)-6-hydroxy-4-(trifluoromethyl)nicotinamide tracer from N-/C-terminal NanoLuc-fused full-length WDR5 (unknown origin) transfected in HEK293T cell lysate incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 15800 nM (pChEMBL 4.800000190734863)
Descriptors: MW 1040.22
Compound (SMILES): N#Cc1ccc(CN2CCC(NC(=O)c3ccc(C(=O)N4CCC(F)(C(=O)c5ccc(F)cc5)CC4)cn3)CC2)cc1
InChIKey: WQUGCKCCOOBUNT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 571.63, ALogP 4.31, HBA 6, HBD 1, PSA 106.4, QED 0.42
Compound (SMILES): N#C[C@H]1C[C@H]1c1c(Cl)ccc2nc(Cn3nc(C(F)(F)F)cc3Cl)cc(=O)n12
InChIKey: GPMGDUIAVSFGGH-PSASIEDQSA-N
Target: Glutamate receptor ionotropic, NMDA 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q12879
Assay: Positive allosteric modulator activity at GluN2A receptor (unknown origin) by FLIPR assay
Measurement: EC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 428.2, ALogP 3.89, HBA 6, HBD 0, PSA 75.98, QED 0.63
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@]4(C)C(=O)c4ccccc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: LOYLCDWZMBZEQT-PFQPMKHESA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat DOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 499.65, ALogP 5.19, HBA 5, HBD 0, PSA 48, QED 0.51
Compound (SMILES): Cc1oc(CN(C)C(=O)CCc2nc(C3CC3)no2)cc1C(=O)O
InChIKey: QFOSACYCLBYVKP-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of human recombinant AKR1C3 transfected in Escherichia coli BL21 (DE3) pLysS competent cells assessed as inhibition of NADP+ dependent oxidation of S-tetralol using S-tetralol as substrate incubated for 10 mins by fluorescence microplate reader assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 333.34, ALogP 2.14, HBA 6, HBD 1, PSA 109.67, QED 0.83
Compound (SMILES): CCCCCC(C)CSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: NTBZIOLBGKVPSB-IYIYPNBDSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged human LEAP2-SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: IC50 = 2.692 nM (pChEMBL 8.569999694824219)
Descriptors: MW 3373
Compound (SMILES): Cc1ccc(CC(C)CNC(=O)/N=C(\N)NCCCc2nnc(N)s2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: WSLRCNVNYUERND-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: Ki = 6.457 nM (pChEMBL 8.1899995803833)
Descriptors: MW 389.53, ALogP 1.85, HBA 5, HBD 4, PSA 131.31, QED 0.31
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(CN5C[C@@H](C)N[C@@H](C)C5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: FXTIMSGNOBJVAE-HDICACEKSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal GST-tagged FGFR3 (436 to 806 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay
Measurement: IC50 = 29.7 nM (pChEMBL 7.53000020980835)
Descriptors: MW 474.61, ALogP 3.94, HBA 6, HBD 3, PSA 91.09, QED 0.36
Compound (SMILES): Clc1ccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)cc1Cl
InChIKey: VFCXPGVHRBRGCL-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 465.39, ALogP 5.6, HBA 4, HBD 2, PSA 75.18, QED 0.31
Compound (SMILES): Clc1ccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: IKADGSKSFBAGRU-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 430.94, ALogP 4.95, HBA 4, HBD 2, PSA 75.18, QED 0.37
Compound (SMILES): CCN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N2CCC(C(=O)OC)CC2)cc1
InChIKey: OTZWZUHDCONCKN-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: Q27783
Assay: Inhibition of recombinant Trypanosoma brucei DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 464.53, ALogP 1.64, HBA 10, HBD 2, PSA 153.45, QED 0.51
Compound (SMILES): CSCC[C@H](C=O)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(C)=O
InChIKey: RJWLAIMXRBDUMH-BRWVUGGUSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 (BetaCoV/Wuhan/WIV04/2019) MPro expressed in Escherichia coli using FRET susbtrate measured after 1 hr
Measurement: IC50 = 970 nM (pChEMBL 6.010000228881836)
Descriptors: MW 401.57, ALogP 1.5, HBA 5, HBD 3, PSA 104.37, QED 0.41
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(F)cc1
InChIKey: BDCBAMRLYXORPZ-UHFFFAOYSA-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 incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 28.9 nM (pChEMBL 7.539999961853027)
Descriptors: MW 393.43, ALogP 5.56, HBA 4, HBD 1, PSA 59.39, QED 0.42
Compound (SMILES): CC(=O)N(C)c1cccnc1Nc1nc(-c2ccc(OC(C)C)cn2)ns1
InChIKey: NOIIUQYBQWFTTJ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 384.47, ALogP 3.51, HBA 8, HBD 1, PSA 93.13, QED 0.69
Compound (SMILES): CC(=O)Nc1nc(Nc2ccc(N3CCN(C)CC3)cc2)sc1C(=O)c1c(Cl)cccc1Cl
InChIKey: ZQXIMAIEMUSYSB-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human recombinant full length GST-tagged CDK4/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 672 nM (pChEMBL 6.170000076293945)
Descriptors: MW 504.44, ALogP 5.13, HBA 7, HBD 2, PSA 77.57, QED 0.45
Compound (SMILES): COC(=O)C1CN(Cc2ccc(-n3cc(-c4ccccc4)nn3)cc2)C1
InChIKey: UHYKKIAHMGSVQF-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 348.41, ALogP 2.54, HBA 6, HBD 0, PSA 60.25, QED 0.66
Compound (SMILES): Cc1cc(-c2cc(C)c(OC[C@@](C)(N)CC(C)C)cn2)ccn1
InChIKey: CIHFEDCEWSFTAE-IBGZPJMESA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 313.45, ALogP 3.9, HBA 4, HBD 1, PSA 61.03, QED 0.88
Compound (SMILES): Cc1cccc(C2NC(=O)c3c(Br)cccc3N2)c1
InChIKey: PXWIXTCIXZCREB-UHFFFAOYSA-N
Target: Protein polybromo-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U86
Assay: Binding affinity to His-TEV-tagged human PBRM1 BD5 transfected in Escherichia coli BL21 (DE3) assessed as dissociation constant at 30 uM by ITC analysis
Measurement: Kd = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 317.19, ALogP 3.61, HBA 2, HBD 2, PSA 41.13, QED 0.84
Compound (SMILES): CCCCC1OC(=O)c2cc(OCc3ccc(CN4CCCC4)c(O)c3)ccc21
InChIKey: YDNLMFWVFUODEG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B by fluorescence assay
Measurement: IC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 395.5, ALogP 4.97, HBA 5, HBD 1, PSA 59, QED 0.64
Compound (SMILES): O=C(O)C1CN(Cc2ccc(-n3cc(-c4ccc(Cl)cc4)nn3)cc2)C1
InChIKey: YBJALHDMRBMVBO-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.82, ALogP 3.1, HBA 5, HBD 1, PSA 71.25, QED 0.75
Compound (SMILES): O=C(O)c1ccc2c(c1)Oc1cnc(OCc3c(-c4c(Cl)cccc4Cl)noc3C3CC3)cc1CC2
InChIKey: CDJOMZYNYHOFGM-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: TR-FRET Farnesoid X Receptor Coactivator Assay: Purchasing invitrogen PV4833 kits.First, the required amount of the compound was weighed and dissolved in 100% DMSO at the maximum concentration of 3000 μM. The solution at the maximum concentration was diluted by 3-fold serial dilution in DMSO to get 10 concentrations;Second, the above prepared solutions of different concentrations were diluted to 100-fold with a buffer supplied with the kit, followed by mixing and then 10 μL of the diluted solution was added to a 384 well plate;Third, nuclear receptor FXR recombinant protein was diluted with a buffer to give a concentration of 4×, and 5 μL of the diluent was added to the 384 well plate of second step;Fourth, Fluorescein-SRC2-2 and Tb anti-GST antibody were diluted with a buffer to give a concentration of 4× respectively. Then two reagents were mixed together, and 10 μL of the mixture was added to the 384 well plate of third step;Finally, the solution of the 384 well above was mixed uniformly by centrifuging, and then incubated at room temperature for 1 h. Then the TR-FRET Endpoint was used for measuring the solution at wavelengths of 520 nm, 495 nm and 337 nm. EC50 values were calculated according to the measured value of ER=520 nm/495 nm.
Measurement: EC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 523.37, ALogP 7.09, HBA 6, HBD 1, PSA 94.68, QED 0.29
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cncc(-c2cnn3cc(-c4cnn(C(C)C)c4)c(O[C@H]4CCOC4)nc23)c1
InChIKey: XKKGIGFZDVPVNO-NGGDXUQASA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human FGFR1 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 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 447.5, ALogP 2.76, HBA 9, HBD 1, PSA 108.46, QED 0.48
Compound (SMILES): O=C(N(CC12CCC(c3nc(C4CC4)no3)(CC1)CC2)c1cccc(-c2nc(C3CC3)no2)c1)C12CC(F)(C1)C2
InChIKey: KBCDUZMEWHIYNA-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant CYP2C9 (unknown origin) using fluorogenic substrate preincubated for 15 min followed by NADPH addition measured after 2 hrs by fluorescence method
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 543.64, ALogP 6.39, HBA 7, HBD 0, PSA 98.15, QED 0.32
Compound (SMILES): COc1cc(Oc2ccc(CNCc3cnc4nc(N)nc(N)c4n3)cc2)cc(OC)c1OC
InChIKey: CIIGLUKLZVOCMA-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: Q27783
Assay: Inhibition of recombinant Trypanosoma brucei DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 463.5, ALogP 2.69, HBA 11, HBD 3, PSA 152.55, QED 0.34
Compound (SMILES): CCCCCCCCc1ccc(C(=O)Nc2ccc(C)cc2C(=O)O)cc1
InChIKey: PFAWUGNNKWJJOU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Binding affinity to full length PLK1 in human PC-3 cells assessed as stabilized protein incubated for 2 hrs followed by aggregation temperature at 56.2 degC by CESTA analysis
Measurement: EC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 367.49, ALogP 5.85, HBA 2, HBD 2, PSA 66.4, QED 0.52
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: OUFAADNZNCCMJZ-BFHRVAIGSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 6.918 nM (pChEMBL 8.15999984741211)
Descriptors: MW 3021.67
Compound (SMILES): COc1cccc2[nH]c(C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C#N)C[C@@H]3CCNC3=O)cc12
InChIKey: ZYTJDBYJYAWQKF-MPGHIAIKSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: SARS-CoV-2 Coronavirus 3C Protease FRET Assay: The proteolytic activity of the main protease, 3CLpro, of SARS-CoV-2 was monitored using a continuous fluorescence resonance energy transfer (FRET) assay. The SARS-CoV-2 3CLpro assay measures the activity of full-length SARS-CoV-2 3CL protease to cleave a synthetic fluorogenic substrate peptide with the following sequence: Dabcyl-KTSAVLQ-SGFRKME-Edans modelled on a consensus peptide (V. Grum-Tokars et al. Evaluating the 3C-like protease activity of SARS-coronavirus: recommendations for standardized assays for drug discovery. Virus Research 133 (2008) 63-73). The fluorescence of the cleaved Edans peptide (excitation 340 nm/emission 490 nm) is measured using a fluorescence intensity protocol on a Flexstation reader (Molecular Devices). The fluorescent signal is reduced in the present of PF-835231, a potent inhibitor of SARS-CoV-2 3CLpro. The assay reaction buffer contained 20 mM Tris-HCl (pH 7.3), 100 nM NaCl, 1 mM EDTA and 25 μM peptide substrate. Enzyme reactions were initiated with the addition of 15 nM SARS-CoV-2 3CL protease and allowed to proceed for 60 minutes at 23° C. Percent inhibition or activity was calculated based on control wells containing no compound (0% inhibition/100% activity) and a control compound (100% inhibition/0% activity). IC50 values were generated using a four-parameter fit model using ABASE software (IDBS). Ki values were fit to the Morrison equation with the enzyme concentration parameter fixed to 15 nM, the Km parameter fixed to 14 μM and the substrate concentration parameter fixed to 25 μM using ABASE software (IDBS).
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 439.52, ALogP 1.86, HBA 5, HBD 4, PSA 136.11, QED 0.47
Compound (SMILES): C=CCN1C(=O)/C(=N\c2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: UWWMPRKPMINKAY-MNDPQUGUSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to human recombinant CA12 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 34.3 nM (pChEMBL 7.460000038146973)
Descriptors: MW 341.39, ALogP 1.99, HBA 4, HBD 1, PSA 92.83, QED 0.86
Compound (SMILES): N#Cc1cccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: HGKCHTOQENPZFF-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 421.51, ALogP 4.17, HBA 5, HBD 2, PSA 98.97, QED 0.39
Compound (SMILES): O=C1NC(Nc2ccc(F)cc2)=N/C1=C\c1ccc2c(c1)OCO2
InChIKey: ZQZULRTVXPNQNP-QPEQYQDCSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of GST-fused mouse recombinant CLK1 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 325.3, ALogP 2.49, HBA 5, HBD 2, PSA 71.95, QED 0.83
Compound (SMILES): COC(=O)Nc1cc(-c2cnc(OC[C@@](C)(N)CC(C)C)cc2C)ccn1
InChIKey: WKLBGGMXGXAZKZ-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 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 372.47, ALogP 3.77, HBA 6, HBD 2, PSA 99.36, QED 0.77
Compound (SMILES): CCS(=O)(=O)n1cc(-c2nc(Nc3cc(Cl)c(N4CCC(N5CCN(C)CC5)CC4)cc3C)ncc2Cl)c2ccccc21
InChIKey: IXOZQNKWHMMWAA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M mutant (unknown origin) by ELISA
Measurement: IC50 = 16.3 nM (pChEMBL 7.789999961853027)
Descriptors: MW 642.66, ALogP 5.87, HBA 9, HBD 1, PSA 86.6, QED 0.27
Compound (SMILES): Cn1cc(-c2cccc(C(=O)Nc3cc(N4CC[C@@H](C(C)(C)O)C4)ncc3C(F)(F)F)n2)cn1
InChIKey: HRRUGRNBEPWHFW-OAHLLOKOSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) assessed as substrate phosphorylation using coumarin and fluorescein-labeled peptide as substrate incubated for 1 hr by Z'-LYTE kinase assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 474.49, ALogP 3.75, HBA 7, HBD 2, PSA 96.17, QED 0.58
Compound (SMILES): N#CCNC(=O)c1ccc(-c2nc(Nc3ccc(N4CCC(N5CCOCC5)CC4)cc3)ncc2F)cc1
InChIKey: OJWUERASKIACOC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Assay: NCEs were screened using in vitro JAK (1, 2 and 3) kinase assay on ADP Glo platform (Promega). Fixed amount of recombinant purified human JAK (25 ng of JAK1 and 10 ng of JAK2 and JAK3 per reaction, from Life Technologies Ltd) were incubated with increasing concentration of NCEs in 1× kinase reaction buffer (40 mM Tris-Cl, pH7.5, 20 mM MgCl2, 0.1 mg/ml BSA and 50 μM DTT). Enzymatic reaction was initiated by adding a substrate cocktail containing 50 μM of ATP (final concentration) and 5 μg for JAK1 and 2.5 μg for JAK2 and JAK3 of polyGln4Tyr1 (Signal Chem) in total 25 μl of reaction in 96 well plate. The reaction was incubated at room temperature for 1 hr.After 1 hr of incubation equal volume (25 μl per reaction) of ADP Glo was added and incubated at room temperature for 40 min.This was followed by addition of kinase detection reagent (50 μl per reaction) and incubation at room temperature for 30 min. Finally, plate was read for luminescence at an integration time of 500 millisecond per well.
Measurement: IC50 = 6.7 nM (pChEMBL 8.170000076293945)
Descriptors: MW 515.59, ALogP 3.58, HBA 8, HBD 2, PSA 106.41, QED 0.46
Compound (SMILES): CC(C)(C)NC(=O)N[C@H](C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(=O)C(N)=O)C2(C)C)C(C)(C)C
InChIKey: XHMGCCSDDIDVLY-QQPKDZIPSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CLpro
Measurement: IC50 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 548.69, ALogP 0.05, HBA 6, HBD 5, PSA 179.8, QED 0.27
Compound (SMILES): CC(C)(C)NC(=O)CC[C@H](NC(=O)CCNC(=O)CCl)C(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)NCc1cccc2ccccc12
InChIKey: SZXRRFKYQZMKHS-ACHIHNKUSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of 20S proteasome subunit beta-1i (unknown origin) using Ac-PAL-AMC as substrate and measured after 30 mins
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 686.25, ALogP 4.26, HBA 5, HBD 5, PSA 145.5, QED 0.12
Compound (SMILES): Fc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1
InChIKey: CGJRUEYHPVXOLI-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 = 22.4 nM (pChEMBL 7.650000095367432)
Descriptors: MW 266.32, ALogP 3.54, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): CC(=O)Nc1ccc(Nc2ncnc(NCCC(=O)OC(C)(C)C)n2)cc1
InChIKey: FQPCIIXSQCSDSG-UHFFFAOYSA-N
Target: Atrial natriuretic peptide receptor 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P41740
Assay: Agonist activity at NPRC in rat aorta assessed as vasorelaxation by Organ bath assay
Measurement: EC50 = 15510 nM (pChEMBL 4.809999942779541)
Descriptors: MW 372.43, ALogP 2.72, HBA 8, HBD 3, PSA 118.13, QED 0.64
Compound (SMILES): Cc1nc([C@@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4cc(F)c(F)c(Cl)c4)nn3)[C@H]2O)n(-c2cc(Cl)ccc2C(F)(F)F)n1
InChIKey: YYBPKCZBLFMASG-WHCFWRGISA-N
Target: Galectin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09382
Assay: Inhibition of His-tagged recombinant human Gal-1 preincubated for 30 mins followed by B-ASF addition measured after 1 hr by time resolved fluorescence based assay
Measurement: IC50 = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 621.35, ALogP 3.83, HBA 10, HBD 3, PSA 131.34, QED 0.23
Compound (SMILES): COc1cc(N(C)CCN(C)C)c(NC(=O)c2ccnc(O)c2)cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
InChIKey: NRRZIKLTKCYGMM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin) by mobility shift assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 566.67, ALogP 4.74, HBA 10, HBD 3, PSA 120.67, QED 0.22
Compound (SMILES): CN1CCN(c2cccc(Nc3nc(N)c(C(=O)c4c(Cl)cccc4Cl)s3)c2)CC1
InChIKey: WMHURJYFLDPMEB-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human recombinant full length GST-tagged CDK4/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 462.41, ALogP 4.76, HBA 7, HBD 2, PSA 74.49, QED 0.53
Compound (SMILES): NS(=O)(=O)c1ccc(N/C=C/C(=O)c2ccccc2)cc1
InChIKey: RQYZWBKWFKVNDK-ZHACJKMWSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 302.36, ALogP 2.14, HBA 4, HBD 2, PSA 89.26, QED 0.65
Compound (SMILES): C[C@]1(CN2Cc3nc(-c4ccc(F)cc4)sc3C2)CN=C(N)O1
InChIKey: WUQLEOOOWJRETO-MRXNPFEDSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 332.4, ALogP 2.37, HBA 6, HBD 1, PSA 63.74, QED 0.94
Compound (SMILES): CCc1cc(Nc2ncc(Br)c(Nc3ccc4nccnc4c3P(C)(C)=O)n2)c(OC)cc1N1CCC(N2CCCN(C)CC2)CC1
InChIKey: FTDDSIYYEHDUAV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) using TK as substrate incubated for 120 mins in the presence of ATP by HTRF assay
Measurement: IC50 = 3003 nM (pChEMBL 5.519999980926514)
Descriptors: MW 722.67, ALogP 6.09, HBA 11, HBD 2, PSA 111.64, QED 0.2
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOCCOc1cc(F)c(Cl)cc1N3
InChIKey: HPMIGMHXZFMMPF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) L858R mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 449.87, ALogP 3.98, HBA 8, HBD 1, PSA 83.96, QED 0.6
Compound (SMILES): O=C(NCC1CCNCC1)c1nc2c(N3CCc4cc(Cl)ccc43)ncnc2s1
InChIKey: XZUIPTFXIKGMGA-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Homo sapiens
UniProt: P06730
Assay: Inhibition of phosphorylation of eIF4E (unknown origin)
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 428.95, ALogP 3.16, HBA 7, HBD 2, PSA 83.04, QED 0.66
Compound (SMILES): CCCCCCCCCCCOc1cccc(CCC(=O)NC[C@@H](O)COP(=O)(O)OC[C@H](NC(=O)C(C)(C)C)C(=O)O)c1
InChIKey: QPUOMUAWXDFZQT-VPUSJEBWSA-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 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 644.74, ALogP 4.76, HBA 8, HBD 5, PSA 180.72, QED 0.08
Compound (SMILES): FC(F)(F)c1cccc(Nc2nc(Nc3ccc(-c4cccs4)cn3)ncc2Cl)c1
InChIKey: DLSMFDJMEDXHOJ-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 1 hr followed by substrate addition and incubated for 60 mins by microplate reader assay
Measurement: IC50 = 396.5 nM (pChEMBL 6.400000095367432)
Descriptors: MW 447.87, ALogP 6.76, HBA 6, HBD 2, PSA 62.73, QED 0.35
Compound (SMILES): C[C@@H](c1ccc(Cl)cc1Cl)n1cnc(-c2ccccc2)c1-c1c(C(=O)Nc2cc(C(=O)O)ccc2N2CCC(N3CCCOC3=O)CC2)[nH]c2cc(Cl)ccc12
InChIKey: GSVXCPWDMIREAJ-DEOSSOPVSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Binding affinity to MDMX (unknown origin) assessed as dissociation constant
Measurement: Kd = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 812.15, ALogP 10.03, HBA 7, HBD 3, PSA 132.79, QED 0.13
Compound (SMILES): C[C@@H]1CCCN1C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(C(O)(C(F)(F)F)C(F)(F)F)c(Cl)c1Cl
InChIKey: ZQHVEGQHOKDZEN-SNVBAGLBSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inhibition of GAL4 DNA-binding domain fused full length human RORbeta (201 to 459 residues) expressed in HEK293T cells incubated for 16 to 20 hrs by one hybrid reporter assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 622.42, ALogP 5.55, HBA 6, HBD 3, PSA 102.76, QED 0.37
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C)c2C)ccn1
InChIKey: LFYHQHOSMHERPO-QFIPXVFZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of full length human AAK1 expressed in HEK293F cells assessed as suppression of AP2 phosphorylation measured after 3 hrs by Western blot analysis based cellular assay
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 385.51, ALogP 4.69, HBA 5, HBD 2, PSA 86.47, QED 0.72
Compound (SMILES): CS(=O)(=O)Nc1ccc(N(Cc2ccccc2)c2ccccc2)cc1
InChIKey: ZQUBXJBFLQZXKR-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P06536
Assay: Displacement of [3H]-dexamethasone from rat glucocorticoid receptor incubated overnight by liquid scintillation counting analysis
Measurement: Ki = 29100 nM (pChEMBL 4.539999961853027)
Descriptors: MW 352.46, ALogP 4.4, HBA 3, HBD 1, PSA 49.41, QED 0.72
Compound (SMILES): O=C1NC(Nc2ccc(O)c(F)c2)=N/C1=C\c1ccc2c(c1)OCO2
InChIKey: AKNIGLLNHUTMPO-XGICHPGQSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of GST-fused mouse recombinant CLK1 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 341.3, ALogP 2.2, HBA 6, HBD 3, PSA 92.18, QED 0.58
Compound (SMILES): Nc1ncc(-c2cc(N3CCOCC3)nc(N3C(=O)OC[C@@H]3CO)n2)c(C(F)(F)F)n1
InChIKey: OWBMLJHHHONAMV-VIFPVBQESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9Z1L0
Assay: Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction in phosphorylation of AKT at Ser473 residue incubated for 1 hr by cellular assay
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 441.37, ALogP 0.69, HBA 10, HBD 2, PSA 139.82, QED 0.7
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(N/N=C/c3ccc([N+](=O)[O-])cc3)nc(Nc3ccccc3)n2)cc1
InChIKey: DCRFQCIXYQUEKJ-ZVHZXABRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA 9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 31.7 nM (pChEMBL 7.5)
Descriptors: MW 505.52, ALogP 3.36, HBA 11, HBD 4, PSA 190.42, QED 0.15
Compound (SMILES): COc1cc2nc(NCCCN3CCCC3)nc(NC3CCN(Cc4ccccc4)CC3)c2cc1OC
InChIKey: PIZBQXXOLNPHSO-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a (unknown origin) assessed as reduction in substrate methylation using histone H3 and SAM as substrate measured after 15 to 60 mins by microfluidic capillary electrophoresis analysis
Measurement: Ki = 4010 nM (pChEMBL 5.400000095367432)
Descriptors: MW 504.68, ALogP 4.62, HBA 8, HBD 2, PSA 74.78, QED 0.37
Compound (SMILES): C=C[C@@]1(C)C=C(C)[C@@H]2[C@@H]3[C@@H](Oc4ccc(cc4)C[C@@]4(O)C/C(=C(/O)[C@H]31)C(=O)N4)[C@@H]1[C@@H](C)C[C@@H](C)C[C@]12C
InChIKey: RHWUVEFQIICMCY-LWZBBKNSSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of human PTP1B
Measurement: IC50 = 89000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 503.68, ALogP 5.71, HBA 4, HBD 3, PSA 78.79, QED 0.43
Compound (SMILES): COc1cc(/C=C2\N=C(Nc3ccc(N4CCCCC4)cc3)NC2=O)ccc1O
InChIKey: RXBPHXFEWBJMNT-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 392.46, ALogP 3.33, HBA 6, HBD 3, PSA 86.19, QED 0.7
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(C(F)(F)F)nc1
InChIKey: GKIGWXXNOVEAKK-UHFFFAOYSA-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 incubated for 2 hrs in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 93.1 nM (pChEMBL 7.03000020980835)
Descriptors: MW 444.42, ALogP 5.84, HBA 5, HBD 1, PSA 72.28, QED 0.36
Compound (SMILES): CCC1C/C(=C\c2cc(OC)c(OC)c(OC)c2Br)C(=O)c2ccccc21
InChIKey: CEQFRYMDADEDKF-RVDMUPIBSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Bos taurus
UniProt: P21398
Assay: Inhibition of recombinant bovine mitochondrial MAO-A using benzylamine or serotonin as substrate incubated for 60 mins by fluorimetry assay
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 431.33, ALogP 5.64, HBA 4, HBD 0, PSA 44.76, QED 0.58
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C/c2cc(Br)cc(Cl)c2O)cc1
InChIKey: WAYVUPNFIKTCOO-REZTVBANSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Binding affinity to AChE (unknown origin) assessed as inhibition constant
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 389.66, ALogP 3.21, HBA 4, HBD 2, PSA 92.75, QED 0.79
Compound (SMILES): Cc1cc(C(=O)NCc2ccc(CN)cc2)c(C)n1Cc1csc(-c2cccnc2)c1
InChIKey: UIJXPAQBXCMOQM-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: KLK1 assay: KLK1 inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stürzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human KLK1 (Callbiochem) was incubated at 37° C. with the fluorogenic substrate H-DVal-Leu-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 430.58, ALogP 4.67, HBA 5, HBD 2, PSA 72.94, QED 0.45
Compound (SMILES): COc1ncc(-c2nc(C(F)(F)F)sc2N2CCN(C(=O)Cn3nc(C)nc3C)[C@H](C)C2)cn1
InChIKey: BEGJXZQGVNJUBB-LLVKDONJSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Antagonist activity at recombinant human CXCR3 in human U2SO cells assessed as reduction in CXCL10-induced beta-arrestin recruitment by TANGO assay
Measurement: IC50 = 558 nM (pChEMBL 6.25)
Descriptors: MW 496.52, ALogP 2.57, HBA 10, HBD 0, PSA 102.16, QED 0.53
Compound (SMILES): CC(C)(O)[C@@H]1CCN(c2cnc(C(F)(F)F)c(NC(=O)c3cccc(-c4cnn(CC5CC5)c4)n3)c2)C1
InChIKey: JKIDUHXOZVXHEI-GOSISDBHSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) assessed as substrate phosphorylation using coumarin and fluorescein-labeled peptide as substrate incubated for 1 hr by Z'-LYTE kinase assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 514.55, ALogP 4.62, HBA 7, HBD 2, PSA 96.17, QED 0.48
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CC3)ccc12
InChIKey: IURJTWHWLCVJAK-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 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 232.24, ALogP 1.01, HBA 3, HBD 2, PSA 74.95, QED 0.83
Compound (SMILES): C=CC(=O)N1CCC(c2cccc(OCC)c2)(c2nnn[nH]2)CC1
InChIKey: BHOBOJXXQSPCML-UHFFFAOYSA-N
Target: Methylcytosine dioxygenase TET3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43151
Assay: Inhibition of GST-tagged human TET3 (49 to 68 residues) expressed in Escherichia coli BL21 cell incubated for 30 mins by fluorescence polarization assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 327.39, ALogP 1.69, HBA 5, HBD 1, PSA 84, QED 0.84
Compound (SMILES): COc1cc(F)ccc1-c1cnc2sc(N3CCC(O)(CN)CC3)nn12
InChIKey: FVVVDLZBHSYIFS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Biological Assay: Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 111× stocks in 100% DMSO. Kds were determined using an 11-point 3-fold compound dilution series with three DMSO control points. All compounds for Kd measurements are distributed by acoustic transfer (non-contact dispensing) in 100% DMSO. The compounds were then diluted directly into the assays such that the final concentration of DMSO was 0.9%. All reactions performed in polypropylene 384-well plate. Each was a final volume of 0.02 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR. Binding constants (Kds) were calculated with a standard dose-response curve using the Hill equation: Response=Background+(Signal−Background)/[1+(KdHill Slope/DoseHill Slope)]
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 377.45, ALogP 1.9, HBA 8, HBD 2, PSA 88.91, QED 0.72
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2ccc(Br)cc2)C(=O)c2ccc(-c3cssc3=S)cc2)cc1
InChIKey: INTKVLJQJDWIIT-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 1042 nM (pChEMBL 5.980000019073486)
Descriptors: MW 605.63, ALogP 6.5, HBA 6, HBD 1, PSA 80.47, QED 0.18
Compound (SMILES): CC(C)(O)C#Cc1ccc2[nH]cc(-c3ccnc(N)n3)c2c1
InChIKey: YYAZUVAPGBAUDQ-UHFFFAOYSA-N
Target: Tau-tubulin kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TCY1
Assay: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay
Measurement: IC50 = 1022 nM (pChEMBL 5.989999771118164)
Descriptors: MW 292.34, ALogP 2.33, HBA 4, HBD 3, PSA 87.82, QED 0.6
Compound (SMILES): Cc1cc(N2CCCC2c2cccnc2)n2ncc(-c3ccccn3)c2n1
InChIKey: YGGNEDPCSSLGDD-UHFFFAOYSA-N
Target: G-protein coupled receptor 39 (SINGLE PROTEIN), Homo sapiens
UniProt: O43194
Assay: Positive allosteric activity at human GPR39 receptor expressed in CHO cells assessed as increase in zn2+ induced ca2+ flux
Measurement: EC50 > 27100 nM (pChEMBL 4.566999912261963)
Descriptors: MW 356.43, ALogP 3.84, HBA 6, HBD 0, PSA 59.21, QED 0.56
Compound (SMILES): Nc1ncc(-c2cc(N3CCOCC3)nc(N3C[C@H](CO)OC3=O)n2)c(C(F)(F)F)n1
InChIKey: DWKKLVKWBYBYKI-SECBINFHSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9Z1L0
Assay: Inhibition of PI3Kbeta in rat Rat1 cells assessed as reduction in phosphorylation of AKT at Ser473 residue incubated for 1 hr by cellular assay
Measurement: IC50 = 124 nM (pChEMBL 6.909999847412109)
Descriptors: MW 441.37, ALogP 0.69, HBA 10, HBD 2, PSA 139.82, QED 0.7
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCOCCOCC(F)(F)c2cnc(-c3ccc(C(C(=O)NO)c4ccccc4F)cc3)nc2)C(C)(C)C)cc1
InChIKey: HCYVFIZSHJPMGM-BZWIJWRHSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant HDAC7 (unknown origin) using Boc-Lys(TFA)-AMC as substrate by fluorescence based plate reader assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 1050.17