lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: IPPNDMWEPHFWFT-PLGODJQZSA-N
Target: Nicotinic acetylcholine receptor alpha6/alpha3/beta4 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12392
Assay: Inhibition of rat alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method
Measurement: IC50 = 2159 nM (pChEMBL 5.670000076293945)
Descriptors: MW 1708.96
Compound (SMILES): CC(NC(=O)Nc1ccc(C(=O)N2CCCCC2)cc1)C12CC3CC(CC(C3)C1)C2
InChIKey: URIYBJNAYURITC-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of mouse recombinant sEH using PHOME as substrate measured after 10 mins by fluorescent based assay
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 409.57, ALogP 5.04, HBA 2, HBD 2, PSA 61.44, QED 0.73
Compound (SMILES): Cc1nccc(N2CCCc3nc(C4(NC(=O)c5ccc(F)cc5)CC4)ccc32)n1
InChIKey: KKAMMYSFTPLTDH-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma/LPS stimulated human whole blood assessed as reduction in kynurenine production using tryptophan as substrate preincubated with compound for 15 mins followed by incubation with IFNgamma/LPS for overnight by LC/MS/MS analysis
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 403.46, ALogP 3.82, HBA 5, HBD 1, PSA 71.01, QED 0.72
Compound (SMILES): CC(C)(Cc1ccc(F)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)c1ccc(-c2ccccc2)cc1
InChIKey: JWQMTWCFNZSLNR-DEOSSOPVSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O75173
Assay: Inhibition of ADAMTS4 by FRET assay
Measurement: IC50 > 22000 nM (pChEMBL 4.6579999923706055)
Descriptors: MW 476.55, ALogP 4.59, HBA 3, HBD 3, PSA 95.5, QED 0.4
Compound (SMILES): Cc1cc(Nc2cc(C)[nH]n2)nc(N2CCC3(CCCN(C(C)c4ccc(-n5cc(F)cn5)nc4)C3=O)CC2)n1
InChIKey: KOQVSAGLGZWLGS-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET V804M mutant (unknown origin)
Measurement: IC50 = 128.7 nM (pChEMBL 6.889999866485596)
Descriptors: MW 544.64, ALogP 4.25, HBA 9, HBD 2, PSA 120.75, QED 0.37
Compound (SMILES): Cc1cc(Nc2cc(C)[nH]n2)nc(N2CCC3(CCCN([C@@H](C)c4ccc(-n5cc(F)cn5)cc4F)C3=O)CC2)n1
InChIKey: SAOJVGXKSANEIE-FQEVSTJZSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET V804M mutant (unknown origin)
Measurement: IC50 = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 561.64, ALogP 4.99, HBA 8, HBD 2, PSA 107.86, QED 0.34
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)N2CCC[C@H](OC)C2)C(=O)N[C@@H](Cc2ccccc2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: YILOYOGEUIDELY-IWJIAYOXSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of chymotrypsin-like activity of human 20s proteasome beta 5c subunit using suc-WLA-AMC as flurogenic substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by fluorescence assay
Measurement: IC50 = 162.6 nM (pChEMBL 6.789999961853027)
Descriptors: MW 594.71, ALogP 2.02, HBA 7, HBD 3, PSA 138.6, QED 0.3
Compound (SMILES): COc1cc2c(cc1Cl)nc(OC)n2CCNC(C)=O
InChIKey: BVSLRGAPRGQWNC-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cells assessed as increase in forskolin induced cAMP production incubated at 37 degreeC by HitHunter-cAMP assay
Measurement: EC50 = 0.063 nM (pChEMBL 10.199999809265137)
Descriptors: MW 297.74, ALogP 1.84, HBA 5, HBD 1, PSA 65.38, QED 0.91
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCN2CCCCC2)CC(=O)NCc2ncco2)nn1C1CCCC1
InChIKey: RWIJUYOOMDLGIL-QFIPXVFZSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human AGTRL1 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 827 nM (pChEMBL 6.079999923706055)
Descriptors: MW 578.71, ALogP 4.35, HBA 9, HBD 2, PSA 123.75, QED 0.31
Compound (SMILES): CC(C)C(c1ccc(-c2ccc3cccc(F)c3c2)[nH]c1=O)N1CCCCS1(=O)=O
InChIKey: HZCRPQODUQCNNZ-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor expressed in CHO cells by cell based cAMP functional assay
Measurement: IC50 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 428.53, ALogP 4.46, HBA 3, HBD 1, PSA 70.24, QED 0.67
Compound (SMILES): O=C(O)c1ccc(Cl)c2c1[nH]c1c3ccc(C(F)(F)F)cc3oc12
InChIKey: UHBYURHTVOBWFN-UHFFFAOYSA-N
Target: Calcium-activated potassium channel subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12791
Assay: Activation of BKca channel (unknown origin) by cell based method
Measurement: EC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 353.68, ALogP 5.44, HBA 2, HBD 2, PSA 66.23, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(OCc4ccccc4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: NGSZOUOYMONWDK-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa2 cells assessed as reduction in lactate production incubated for 2 hrs by fluorescence based assay
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 618.71, ALogP 5.6, HBA 8, HBD 2, PSA 137.4, QED 0.2
Compound (SMILES): COc1cc2c(cc1OCC1CC1)CCN1CC(CC(C)C)C(O)CC21
InChIKey: HSVRNWDLNHQKIR-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]DA uptake at VMAT2 in rat striatal synaptosome incubated for 10 mins followed by [3H]DA addition and measured after 20 mins by TopCount scintillation counting method
Measurement: IC50 = 17.83 nM (pChEMBL 7.75)
Descriptors: MW 359.51, ALogP 3.81, HBA 4, HBD 1, PSA 41.93, QED 0.84
Compound (SMILES): Cc1c(CN2CCN(C(=O)c3cc4cccc(C(N)=O)c4o3)CC2)sc2c(N3CCOCC3)nc(-c3ccc(N)nc3)nc12
InChIKey: RJIZKFOPJCXLAT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 40 mins by ADP-glo plus luminescence assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 612.72, ALogP 3.28, HBA 11, HBD 2, PSA 156.94, QED 0.29
Compound (SMILES): C[C@H](O)CNc1cc(Oc2ccc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2)ncn1
InChIKey: BUJLMFKZIJWAPL-ZDUSSCGKSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of GST-6His tagged VEGFR2 (unknown origin) using biotin-aminohexyl-EEEEYFELVAKKKK-NH2 peptide substrate incubated for 90 mins by HTRF assay
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 447.42, ALogP 4.72, HBA 6, HBD 4, PSA 108.4, QED 0.42
Compound (SMILES): COc1ccc(OC)c(-n2nnc(S(=O)(=O)c3ccc(C(C)(C)OC)cc3)c2C)c1
InChIKey: LJPCPXYDKHSNBM-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Inverse agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 431.51, ALogP 3.31, HBA 8, HBD 0, PSA 92.54, QED 0.57
Compound (SMILES): C/C(=C\CC[C@]1(C)CCc2c(C)c(O)c(C)c(C)c2O1)CC/C=C(\C)CCC(=O)O
InChIKey: LAVCYAUSHCEKED-KYVGBUAPSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX in human PMNL assessed as reduction in 5-LOX product formation preincubated for 10 mins before addition of AA and A23187 and measured after 10 mins by RP-HPLC method
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 414.59, ALogP 6.72, HBA 3, HBD 2, PSA 66.76, QED 0.44
Compound (SMILES): CN(C)C(=O)CNc1ccc2c(c1)C[C@@H](NC[C@H](O)c1ccc(O)c(CCO)c1)CC2
InChIKey: SYZFCJKHFMUOAG-REWPJTCUSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at human beta1 adrenoceptor expressed in CHO cells assessed as increase in cAMP level incubated for 30 mins by immunoassay
Measurement: EC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 427.55, ALogP 1.61, HBA 6, HBD 5, PSA 105.06, QED 0.42
Compound (SMILES): COc1ccc(S(=O)(=O)N(C[C@@H](O)[C@H](Cc2ccccc2)NC(=O)/C=C/c2cc(OC)c(O)c(OC)c2)C(C)C)cc1
InChIKey: BDPJBXBDASBMKE-SGJYFDFBSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of wild type HIV1 protease expressed in Escherichia coli using Arg-Glu (EDANS)-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-Lys(DABCYL)-Arg as substrate preincubated for 20 to 30 mins followed by substrate addition and measured for 10 mins by FRET assay
Measurement: IC50 = 527.2 nM (pChEMBL 6.28000020980835)
Descriptors: MW 598.72, ALogP 3.62, HBA 8, HBD 3, PSA 134.63, QED 0.24
Compound (SMILES): NCCCCc1cn(-c2ccc(-c3nc(-c4ccc5c(c4)OCC5)cs3)c(OCCN3CCNC3=O)c2)nn1.O=C(O)C(F)(F)F
InChIKey: FDMUICROIBDLGM-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Inhibition of recombinant His-FLAG-tagged Leishmania infantum TryR dimerization expressed in Escherichia coli BL2(DE3) assessed as reduction in TryR dimer using TS2 as substrate after 16 hrs by ELISA
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 545.67, ALogP 3.68, HBA 9, HBD 2, PSA 120.42, QED 0.28
Compound (SMILES): CSc1ccccc1NC1=C(c2ccccc2C(F)(F)F)C(=O)NC1=O
InChIKey: DCMFAJFUAUDBKN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O94804
Assay: Binding affinity human STK10 by binding displacement assay
Measurement: Ki = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 378.38, ALogP 3.91, HBA 4, HBD 2, PSA 58.2, QED 0.63
Compound (SMILES): COc1cc(C(C)=O)c(C)cc1-n1nnc(S(=O)(=O)c2ccc(C(C)(C)C)cc2)c1C
InChIKey: RTPVFHLNGWTLNH-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay
Measurement: EC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 441.55, ALogP 4.23, HBA 7, HBD 0, PSA 91.15, QED 0.55
Compound (SMILES): COc1ccc2ncc(F)c(C(O)C[C@H]3OC[C@H](NCc4ccc5c(n4)NC(=O)CS5)CO3)c2n1
InChIKey: IBUUDJJQWLQLAV-PRYQSJQGSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus topoisomerase IV decatenation activity using kDNA as substrate by ethidium bromide/bromophenol blue staining based agarose gel electrophoresis analysis
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 501.54, ALogP 2.17, HBA 10, HBD 3, PSA 127.72, QED 0.44
Compound (SMILES): Fc1ccc2c(C3CCN(CCCOc4ccc(CN5CCCCC5)cc4F)CC3)noc2c1
InChIKey: FFUYAMBLAURQHK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to 5-HT1A receptor (unknown origin)
Measurement: Ki = 90.6 nM (pChEMBL 7.039999961853027)
Descriptors: MW 469.58, ALogP 5.74, HBA 5, HBD 0, PSA 41.74, QED 0.39
Compound (SMILES): Cn1c(=O)c(-c2ccc(Cl)cc2Cl)cc2cnc(Nc3cccc(S(C)(=O)=O)c3)nc21
InChIKey: DHLDFZDYTZKHEN-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Inhibition of human NOD2 expressed in HEK-blue cells coexpressing NFkappaB-SEAP reporter assessed as reduction in L18-MDP-induced NF-kappaB activation preincubated for 15 mins followed by L18-MDP stimulation and further incubated for 8 hrs by SEAP reporter gene assay
Measurement: IC50 = 878 nM (pChEMBL 6.059999942779541)
Descriptors: MW 475.36, ALogP 4.45, HBA 7, HBD 1, PSA 93.95, QED 0.47
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)ncc1[nH]c(=O)n(CC(C)C)c12
InChIKey: MLTXFGXFWPBTLM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from recombinant human N-terminal 6His-tagged BRD4-BD1 Y390A mutant (1 to 477 residue) expressed in Escherichia coli incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 366.42, ALogP 3.81, HBA 6, HBD 1, PSA 85.94, QED 0.59
Compound (SMILES): O=C(Nc1nc2cc(O)c(O)cc2s1)c1ccc(-c2ccccc2)cc1
InChIKey: AVYZWRLSSXRNIK-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of DENV2 NS2B-NS3 protease expressed in Escherichia coli BL21(DE3) using Boc-Gly-Arg-Arg-AMC as substrate by FRET assay
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 362.41, ALogP 4.63, HBA 5, HBD 3, PSA 82.45, QED 0.46
Compound (SMILES): CC(C)C(O)(C(=O)O)c1ccc(-c2ccc3ccccc3c2)[nH]c1=O
InChIKey: UQOOVEPSYQCYEG-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor expressed in CHO cells by cell based cAMP functional assay
Measurement: IC50 = 1580 nM (pChEMBL 5.800000190734863)
Descriptors: MW 337.38, ALogP 3.12, HBA 3, HBD 3, PSA 90.39, QED 0.68
Compound (SMILES): c1ccc([C@@H]2CCC[C@H](CCN3CCN(c4ccccc4)CC3)O2)cc1
InChIKey: BEZXRTIXFCIASE-PKTZIBPZSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor in rat liver membrane by solid scintillation counting method
Measurement: Ki = 161 nM (pChEMBL 6.789999961853027)
Descriptors: MW 350.51, ALogP 4.51, HBA 3, HBD 0, PSA 15.71, QED 0.79
Compound (SMILES): O=C(O)c1cccc(COc2ccc(C(F)(F)F)cc2Cl)c1
InChIKey: XADPXIHQQNNXFK-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 10 uM of bilirubin by HTRF assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 330.69, ALogP 4.64, HBA 2, HBD 1, PSA 46.53, QED 0.89
Compound (SMILES): CC(=O)N1CCN(c2ccc(Nc3ncc(Cl)c(Nc4cccc(C(F)(F)F)c4)n3)nc2)CC1
InChIKey: YLTAJZAGZXAKKF-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human THP-1 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 491.91, ALogP 4.7, HBA 7, HBD 2, PSA 86.28, QED 0.53
Compound (SMILES): C#Cc1cccc(Nc2ncnc3cc(OC)c(OCCCCCCCN/C(=N\C#N)Nc4cccnc4)cc23)c1
InChIKey: WZVDJOCODASVRT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human recombinant EGFR cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system by Z'-LYTE kinase assay
Measurement: IC50 = 0.538 nM (pChEMBL 9.270000457763672)
Descriptors: MW 548.65, ALogP 5.63, HBA 8, HBD 3, PSA 129.37, QED 0.06
Compound (SMILES): C[C@H](NC(=O)[C@H](CCCNC(=N)N)NCCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1)C(=O)NC(=O)[C@@H](N)CCCN.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: IUQOTECUSULCDW-BMCJDKOGSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 0.1047 nM (pChEMBL 9.979999542236328)
Descriptors: MW 860.12, ALogP 0.85, HBA 12, HBD 9, PSA 260.37, QED 0.05
Compound (SMILES): CNc1cc(Oc2ccc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2C)ncn1
InChIKey: FWRYZOIOCJCFQT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of GST-6His tagged VEGFR2 (unknown origin) using biotin-aminohexyl-EEEEYFELVAKKKK-NH2 peptide substrate incubated for 90 mins by HTRF assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 417.39, ALogP 5.28, HBA 5, HBD 3, PSA 88.17, QED 0.53
Compound (SMILES): C=CC(=O)N1CCC[C@H](CC(=O)N2Cc3[nH]c4ccccc4c3C[C@@H]2C(=O)NC)C1
InChIKey: JZCPISYHINOJCA-FOIQADDNSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human N-terminal His-tagged BTK C481S mutant expressed in baculovirus infected in Sf9 cells incubated for 1 hr by TR-FRET assay
Measurement: IC50 > 5920 nM (pChEMBL 5.228000164031982)
Descriptors: MW 408.5, ALogP 1.98, HBA 3, HBD 2, PSA 85.51, QED 0.76
Compound (SMILES): C=CC(=O)N1CCN(c2c(C#N)c(=O)n(-c3c(C)ccnc3C(C)C)c3nc(-c4c(N)c(Cl)cc(Cl)c4F)c(Cl)cc23)C[C@@H]1CC#N
InChIKey: UAMGUBVJXVAZNT-SFHVURJKSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as reduction in ERK phosphorylation incubated for 2 hrs by HTRF assay
Measurement: IC50 = 12.25 nM (pChEMBL 7.909999847412109)
Descriptors: MW 694, ALogP 6.55, HBA 9, HBD 1, PSA 144.93, QED 0.14
Compound (SMILES): COc1ccccc1C1CC1CNCCCCCOc1ccc2c(c1)NC(=O)CC2
InChIKey: VPLIPKULMVANPA-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method
Measurement: Ki = 257.04 nM (pChEMBL 6.590000152587891)
Descriptors: MW 408.54, ALogP 4.52, HBA 4, HBD 2, PSA 59.59, QED 0.54
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: NPTYEQVKIVHBRN-PSWJWLENSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Agonist activity at mouse MC3R expressed in HEK293 cells assessed as induction of cAMP level incubated for 2 hr by alphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 765.92, ALogP 0.75, HBA 7, HBD 11, PSA 283.29, QED 0.03
Compound (SMILES): Cc1c(F)nccc1[C@H]1CC[C@@H]([C@@H](C)NC(=O)c2ccc(Cl)cc2)CC1
InChIKey: BKKNXJMEJMBLAM-OAGGEKHMSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by recombinant murine IFNgamma stimulation and measured after 18 hrs by fluorescence based microplate reader assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 374.89, ALogP 5.27, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): COc1ccc(Cl)cc1C1CC1CNCCCCOc1ccc2c(c1)NC(=O)CC2
InChIKey: AODRELZHCYHJFT-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method
Measurement: Ki = 38.02 nM (pChEMBL 7.420000076293945)
Descriptors: MW 428.96, ALogP 4.79, HBA 4, HBD 2, PSA 59.59, QED 0.53
Compound (SMILES): O=S(=O)(Nc1cccc(F)n1)c1cc(F)c(O[C@H]2CCN(CC(F)(F)F)C[C@@H]2c2ccccc2)cc1F
InChIKey: WSTNZILNGXCYBM-APWZRJJASA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 VSD2 R814A mutant by automated voltage clamp electrophysiology
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 545.51, ALogP 5.1, HBA 5, HBD 1, PSA 71.53, QED 0.33
Compound (SMILES): CC1(CCC(=O)N2CCN(c3ccccc3)CC2)NC(=O)NC1=O
InChIKey: WYQZHRISWNRPRD-UHFFFAOYSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNA0
Assay: In Vitro Assay: ADAMTS-5:Protocol 1: The basis for the assay is the cleavage of the substrate TBIS-1 (5 FAM-TEGEARGSVILLK (5TAMRA)K-NH2) (SEQ ID No 2) by human ADAMTS-5.For the dose response (10 point), 4 μL of a dilution series of compound (2 mM highest concentration, 1/5 dilution in DMSO further diluted 1 in 10 in water, corresponding to a final highest concentration of 20 μM), is transferred to 384 well Fluotrac 200 plate (Greiner, cat #781076) and incubated at room temperature for 30 min with a 26 μL buffer solution (50 mM Hepes pH7.5, 100 mM NaCl, 5 mM CaCl2, 0.1% CHAPS, 5% glycerol) containing hADAMTS-5 (0.5 ng/L) (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration).The reaction is initiated by adding to the assay plate TBIS-1 (10 μL, 4.5 μM, Anaspec) in the same buffer.Finally, the fluorescence is read on the Envision (Perkin Elmer) after an incubation of 60 min at Room Temperature (Excitation 485 nm, emission 530).
Measurement: IC50 = 694 nM (pChEMBL 6.159999847412109)
Descriptors: MW 330.39, ALogP 0.71, HBA 4, HBD 2, PSA 81.75, QED 0.8
Compound (SMILES): CCn1c(-c2ccc(C(F)(F)F)nc2)nc2c(O[C@H]3CCN(C(=O)[C@H]4C[C@@H](OC)C4)C3)ncnc21
InChIKey: GXAZJAYXDSNEPR-HRCADAONSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in anti-IgM-antibody-induced phosphorylation of AKT at Ser473 residue preincubated for 20 mins followed by anti-IgM antibody stimulation and measured after 30 mins by alphascreen assay
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 490.49, ALogP 3.33, HBA 8, HBD 0, PSA 95.26, QED 0.52
Compound (SMILES): COc1ccccc1C1=C(Nc2ccc(OCc3ccccc3)c(Cl)c2)C(=O)NC1=O
InChIKey: UKFZPGOREAWYIK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O94804
Assay: Binding affinity human STK10 by binding displacement assay
Measurement: Ki = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 434.88, ALogP 4.41, HBA 5, HBD 2, PSA 76.66, QED 0.54
Compound (SMILES): O/N=C(/Nc1cccc(Cl)c1)c1ccc2oc(-c3ccccc3)cc2c1
InChIKey: UXTLAAKGFIRWCS-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate by absorbance based analysis
Measurement: IC50 = 10800 nM (pChEMBL 4.96999979019165)
Descriptors: MW 362.82, ALogP 6, HBA 3, HBD 2, PSA 57.76, QED 0.2
Compound (SMILES): CCOc1ccc(CCc2nc3cc(-c4c(C)noc4C)ccn3c2NC2CCCCC2)cc1
InChIKey: AYYCXCROSXTBJD-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 BD1 (unknown origin) using biotinylated-JQ1 peptide as substrate incubated for 1 hr by AlphaScreen assay
Measurement: IC50 = 6480 nM (pChEMBL 5.190000057220459)
Descriptors: MW 458.61, ALogP 6.53, HBA 6, HBD 1, PSA 64.59, QED 0.32
Compound (SMILES): Cc1ncc([N+](=O)[O-])n1CCOc1cccc(/C=N\c2ccc(S(=O)(=O)Nc3nccs3)cc2)c1
InChIKey: KQALYPOUOCHSCK-QFEZKATASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 512.57, ALogP 4.19, HBA 10, HBD 1, PSA 141.61, QED 0.19
Compound (SMILES): CCN(CC)c1ccc2c(C)c(CCN3C(=O)NC4(CCN(c5ncnc6[nH]cnc56)C4)C3=O)c(=O)oc2c1
InChIKey: GJGVESGTTVTGQA-UHFFFAOYSA-N
Target: Immunoglobulin lambda variable 6-57 (SINGLE PROTEIN), Homo sapiens
UniProt: P01721
Assay: Stabilization of AL patient derived full length fluorescein-labeled IGLV6-57 expressed in Escherichia coli BL21 (DE3) measured after 24 hrs by proteolysis coupled-fluorescence polarization assay
Measurement: EC50 = 551 nM (pChEMBL 6.260000228881836)
Descriptors: MW 530.59, ALogP 2.36, HBA 9, HBD 2, PSA 140.56, QED 0.27
Compound (SMILES): CC(C)=CCC1=C(O)c2ccccc2/C(=N/NC(N)=S)C1=O
InChIKey: PINSRXIFMHJTJZ-AQTBWJFISA-N
Target: Rhodesain (SINGLE PROTEIN), Trypanosoma brucei rhodesiense
UniProt: Q95PM0
Assay: Inhibition of recombinant Trypanosoma brucei rhodesain using Z-FR-AMC as substrate preincubated for 10 mins followed by substrate addition measured for 5 mins by fluorimetric analysis relative to control
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 315.4, ALogP 2.43, HBA 4, HBD 3, PSA 87.71, QED 0.45
Compound (SMILES): Cc1ccc(S(=O)(=O)NCC(C)(C)O)cc1-c1cnc(N)c(-c2cnn(C)n2)c1
InChIKey: OUGWFIXWGKIEGR-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as substrate incubated for 30 to 60 mins in presence of ATP by Kinase Glo luminescence kinase assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 416.51, ALogP 1.48, HBA 8, HBD 3, PSA 136.02, QED 0.55
Compound (SMILES): COc1ccc(-c2cc(O[C@@H]3CCN(C(=O)C4CC4)C3)cc3c2CNC3=O)cn1
InChIKey: WBWXYWNAKKEBAS-OAHLLOKOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) by HTRF assay
Measurement: IC50 = 1891 nM (pChEMBL 5.71999979019165)
Descriptors: MW 393.44, ALogP 2.39, HBA 5, HBD 1, PSA 80.76, QED 0.84
Compound (SMILES): Nc1cc(Cc2ccn(Cc3cccc(C4CCNCC4)c3)n2)c2nn[nH]c2n1
InChIKey: GTNPNVTWXDESRL-UHFFFAOYSA-N
Target: Thyroid peroxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P07202
Assay: Inhibition of C-terminal hexaHis-tagged TPO (unknown origin) expressed in Trichoplusia ni insect cells using 3-iodo tyrosine as substrate preincubated for 10 mins followed by substrate and H2O2 addition and further incubated for 15 mins
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 388.48, ALogP 2.24, HBA 7, HBD 3, PSA 110.33, QED 0.48
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2ccn(Cc3cccc(F)c3)n2)C[C@@H]1O
InChIKey: PJHUELIKSXLGBB-OGWOLHLISA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13564
Assay: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay
Measurement: IC50 = 357 nM (pChEMBL 6.449999809265137)
Descriptors: MW 490.52, ALogP 0.86, HBA 10, HBD 3, PSA 162.32, QED 0.37
Compound (SMILES): COc1cccc(OC)c1-n1c(-c2cncc(C)c2)nc(=O)c(S(=O)(=O)c2ccc(C3CC3)cc2)c1O
InChIKey: LUQOFNBOLNRSAK-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q9WV08
Assay: Agonist activity at mouse APJ receptor assessed as effect on cAMP accumulation by cAMP-Glo assay
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 519.58, ALogP 4.04, HBA 9, HBD 1, PSA 120.61, QED 0.39
Compound (SMILES): CC(C)CCc1cccc(C(=O)Nc2c(O)c3ccc(NS(=O)(=O)Cc4ccccc4)cc3oc2=O)c1
InChIKey: HFOSAWWSLUZQAF-UHFFFAOYSA-N
Target: Microtubule-associated protein 1 light chain 3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H492
Assay: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3A by time-resolved FRET assay
Measurement: IC50 = 73100 nM (pChEMBL 4.139999866485596)
Descriptors: MW 520.61, ALogP 5.28, HBA 6, HBD 3, PSA 125.71, QED 0.26
Compound (SMILES): CCCCC1NC(C)(C)C(=O)N1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
InChIKey: GGJHROCBQKSZQF-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Antagonist activity at human AT1 overexpressed in CHO-K1 cells in presence of 10 nM [Val5-angiotensin II measured after 90 mins by HTRF based IP-one assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 404.52, ALogP 3.76, HBA 5, HBD 2, PSA 86.8, QED 0.63
Compound (SMILES): O=C(O)CCNC(=S)NCCCNc1nc(NCc2ccccc2)ncc1Br
InChIKey: SRAQSHZOSZIXDT-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate in presence of NAD+ by fluorescence based analysis
Measurement: IC50 = 6966.27 nM (pChEMBL 5.159999847412109)
Descriptors: MW 467.39, ALogP 2.59, HBA 6, HBD 5, PSA 111.2, QED 0.25
Compound (SMILES): CN1CCC(Oc2ccc(N3C(=S)N(c4cnc(C#N)c(C(F)(F)F)c4)C(=O)C34CCC4)cn2)CC1
InChIKey: QWOXNKRFQAABQG-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR wild-type (unknown origin) transfected in human LNCAP cells cotransfected with ARE-LUC incubated for 20 to 24 hrs in presence of AR agonist R1881 by steady-glo luciferase reporter gene assay
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 516.55, ALogP 3.9, HBA 7, HBD 0, PSA 85.59, QED 0.57
Compound (SMILES): CCOc1ccc(-c2ccc(CO[C@H]3C[C@@H](N=C=S)C3)c(F)c2)cc1F
InChIKey: SZKZHHKMMVQLJL-CALCHBBNSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 375.44, ALogP 5.18, HBA 4, HBD 0, PSA 30.82, QED 0.49
Compound (SMILES): COc1ccc(CNc2cccc([C@H]3C[C@@]45CC[C@]3(OC)[C@@H]3Oc6c(O)ccc7c6[C@@]34CCN(CC3CC3)[C@@H]5C7)c2)cc1
InChIKey: XQEPCIDYOYBHDP-BNZUBNTLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat delta opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 0.072 nM (pChEMBL 10.140000343322754)
Descriptors: MW 578.75, ALogP 6.41, HBA 6, HBD 2, PSA 63.19, QED 0.32
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc(Oc3ncnc4c3CCN(CC3CN(C)C3)C4)c(F)c2)c(=O)n(-c2ccc(F)cc2)c1=O
InChIKey: ATNVOCQRWNYCHO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of Mer (unknown origin) by cell free assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 617.66, ALogP 3.61, HBA 10, HBD 1, PSA 114.59, QED 0.32
Compound (SMILES): COC(=O)c1sc2nc3c(cc2c1N)CN(Cc1ccccc1)CC3
InChIKey: AADJALJXYKSCIB-UHFFFAOYSA-N
Target: Urea transporter 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97689
Assay: Inhibition of rat UT-B incubated for 15 mins
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 353.45, ALogP 3.22, HBA 6, HBD 1, PSA 68.45, QED 0.73
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccc(CNC(=O)c5ccc(OC(F)(F)F)cc5)c(F)c4)ccnc3[nH]2)cn1
InChIKey: HBVFTEZRJAHDNL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Microfluidic Off-Chip Mobility Shift Assay Protocol for Potency Assessment Against BTK C481S Enzyme: The protocol below describes a microfluidic, off-chip mobility shift kinase assay to measure inherent potency of compounds against BTK C481S enzyme. The mechanics of the assay platform are described by the vendor (PerkinElmer, Hopkinton, Mass.) on their website at the following URL: http://caliperls.com.Briefly, 2.5× stocks of His-TEV-hsBTK(328-659)(C481S) from the Merck Serono Protein Purification Laboratory in Darmstadt, Germany (PCS, Q27/234), 1.6×ATP and appropriate KinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2; Tufts University Core Facility custom synthesis) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM HEPES, pH 7.5, and 10 mM DTT.5 uL of enzyme buffer and 7.5 uL of ATP/KinKDR peptide substrate mix were added to Matrix (#4315) 384-well, sterile, flat-bottom polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 25° C. Following the incubation period, reactions were terminated by adding 65 uL quench buffer consisting of 100 mM HEPES, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (PerkinElmer, Mountain View, Calif.), 5% DMSO. Terminated reactions were monitored at −2 PSI, −3000 V/−700 Volts in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was quantified by laser-induced fluorescence measuring the charge/mass difference between substrate and product resulting from peptide phosphorylation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel, Switzerland).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 510.45, ALogP 4.99, HBA 6, HBD 2, PSA 97.72, QED 0.31
Compound (SMILES): CN(C)Cc1ccc(CNC(=O)c2ccc3nncn3c2)cc1
InChIKey: INYAZFZIPMYIQV-UHFFFAOYSA-N
Target: Protein AF-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P42568
Assay: Inhibition of human His-AF9 YEATS domain and biotinylated H3K9ac peptide interaction by AlphaScreen assay
Measurement: IC50 = 4934 nM (pChEMBL 5.309999942779541)
Descriptors: MW 309.37, ALogP 1.72, HBA 5, HBD 1, PSA 62.53, QED 0.78
Compound (SMILES): Cc1cc(-c2ccc(Cl)cc2Cl)c2ncn(C)c(=O)c2c1
InChIKey: RSKHPANXURRXHS-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity at PAR4 in human platelet-rich plasma assessed as inhibition of PAR4 AP AYPGKF-NH2-induced platelet aggregation by photo-turbidimetry assay
Measurement: IC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 319.19, ALogP 4.22, HBA 3, HBD 0, PSA 34.89, QED 0.67
Compound (SMILES): FC(F)(F)c1cccc(Nc2ccnc(Nc3ccc(-c4ccsc4)cn3)n2)c1
InChIKey: PKDJMOPRADKMKS-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human THP-1 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 92.4 nM (pChEMBL 7.03000020980835)
Descriptors: MW 413.43, ALogP 6.11, HBA 6, HBD 2, PSA 62.73, QED 0.41
Compound (SMILES): C#Cc1cccc(Nc2ncnc3cc(OC)c(OCCCCC(=O)Nc4ccc(S(N)(=O)=O)cc4)cc23)c1
InChIKey: JRWOGXREMCUZPF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR T790M mutant (669 to 1210 residues) expressed in baculovirus expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 48.5 nM (pChEMBL 7.309999942779541)
Descriptors: MW 545.62, ALogP 4.2, HBA 8, HBD 3, PSA 145.53, QED 0.19
Compound (SMILES): COc1ccccc1-c1ccc(-c2nnc(N(C)Cc3ccc4nccn4c3)o2)cc1
InChIKey: GUZYREPIQDATAM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by LC-MS analysis
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 411.47, ALogP 4.7, HBA 7, HBD 0, PSA 68.69, QED 0.4
Compound (SMILES): CCNC(=O)c1cc(Cc2ccccc2)nc(-c2cn(C)nn2)c1
InChIKey: XEUFGJQUVDKHST-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of 6His-Thr-BRD4 (1 to 477 residues) BD2 domain Y390A mutant (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 321.38, ALogP 2.22, HBA 5, HBD 1, PSA 72.7, QED 0.78
Compound (SMILES): O=c1ccc2ccc(OCCCCNCC3CC3c3cccc4c3OCCO4)cc2[nH]1
InChIKey: IENYPQKJOPZPRI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method
Measurement: Ki = 177.83 nM (pChEMBL 6.75)
Descriptors: MW 420.51, ALogP 3.85, HBA 5, HBD 2, PSA 72.58, QED 0.51
Compound (SMILES): CC(C)(O)COc1nc(OCCCC(F)(F)F)c(CO)cc1-c1ccc(S(C)(=O)=O)cc1
InChIKey: XJUNHUOEBRIQIM-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of human recombinant COX-1 assessed as reduction in peroxidase activity using arachidonic acid as substrate preincubated for 60 mins followed by substrate addition for 2 secs by ADPH based fluorometric analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 477.5, ALogP 3.52, HBA 7, HBD 2, PSA 105.95, QED 0.5
Compound (SMILES): CC(C)c1ccc(CNC(=O)C2CCCN(c3cccc(OC(C)(C)C(=O)O)c3)C2)cc1
InChIKey: RWRLBVSCKJARNJ-UHFFFAOYSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of full length C-terminal 6-His-tagged beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-N-terminal biotinylated human BCL9 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: Ki = 71000 nM (pChEMBL 4.150000095367432)
Descriptors: MW 438.57, ALogP 4.58, HBA 4, HBD 2, PSA 78.87, QED 0.63
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)ncc1[nH]c(=O)n(CC3CCN(C)CC3)c12
InChIKey: NMAADMLFZSMLHC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from recombinant human N-terminal 6His-tagged BRD4-BD1 Y390A mutant (1 to 477 residue) expressed in Escherichia coli incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 421.5, ALogP 3.5, HBA 7, HBD 1, PSA 89.18, QED 0.54
Compound (SMILES): Cc1cc([C@H]2CC[C@@H]([C@@H](C)NC(=O)c3ccc(Cl)cc3)CC2)ccn1
InChIKey: IBPKEMIBZFVABE-ZACQAIPSSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by recombinant murine IFNgamma stimulation and measured after 18 hrs by fluorescence based microplate reader assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 356.9, ALogP 5.14, HBA 2, HBD 1, PSA 41.99, QED 0.82
Compound (SMILES): O=C(O)CCNC(=S)NCCCNc1nc(CCc2ccccc2)ncc1I
InChIKey: SSDOGBXCEHCYEA-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate in presence of NAD+ by fluorescence based analysis
Measurement: IC50 = 6982.32 nM (pChEMBL 5.159999847412109)
Descriptors: MW 513.4, ALogP 2.61, HBA 5, HBD 4, PSA 99.17, QED 0.21
Compound (SMILES): Cc1ccccc1CCCNCC(O)c1ccc(O)c2[nH]c(=O)ccc12.Cl
InChIKey: MKEAFKZFOCGOAS-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation
Measurement: EC50 = 0.05754 nM (pChEMBL 10.239999771118164)
Descriptors: MW 352.43, ALogP 2.8, HBA 4, HBD 4, PSA 85.35, QED 0.49
Compound (SMILES): Nc1cc(C2CCNCCc3cccc(c3)OCc3cccc(c3)Cn3cc2cn3)c2nn[nH]c2n1
InChIKey: YIZLIFDTJLQOKE-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: MPO Peroxidation Assay (Amplex Red Assay): MPO peroxidation activity was measured in 100 mM KPi (pH 7.4) by utilizing the non-fluorescent reagent Amplex Red (Invitrogen Cat. #A12222) which can be oxidized to the highly fluorescent resorufin. Amplex Red is oxidized by the peroxidase action of MPO to resorufin. Reactions were carried out in 50 μL total volume by adding a 25 μL mixture of 200 pM myeloperoxidase and 40 nM H2O2 (Sigma #349887) to 100 nL inhibitor in 100% DMSO in a 384 well Perkin Elmer Optiplate. Enzyme and compound were preincubated for ten minutes at room temperature.After the ten minute preincubation, 25 μL of an Amplex Red mixture containing 200 μM Amplex Red and 10 mM H2O2 was added to the plate. Kinetic determinations were carried out immediately on a Perkin Elmer Envision (15 minute kinetic read, Ex: 535 nm, Em: 590 nm).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 480.58, ALogP 3.43, HBA 8, HBD 3, PSA 119.56, QED 0.34
Compound (SMILES): Cc1c(CN2CCN(C(=O)c3cc4cccc(C(N)=O)c4o3)CC2)sc2c(N3CCOCC3)nc(-c3ccc(N)c(F)c3)nc12
InChIKey: BFQFZYAAJSFZQT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 40 mins by ADP-glo plus luminescence assay
Measurement: IC50 = 1176 nM (pChEMBL 5.929999828338623)
Descriptors: MW 629.72, ALogP 4.03, HBA 10, HBD 2, PSA 144.05, QED 0.27
Compound (SMILES): COc1ccc(-c2nn(-c3ccc(Cl)cc3)cc2/C=C/c2cc(C(=O)N3CCOCC3)c3cc(Cl)ccc3n2)cc1
InChIKey: UTIFXRVYZVJPBY-KRXBUXKQSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX-2 using arachidonic acid as substrate preincubated with enzyme for 5 mins followed by incubation with substrate for 5 mins by colorimetric analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 585.49, ALogP 7.05, HBA 6, HBD 0, PSA 69.48, QED 0.21
Compound (SMILES): Cn1c(SCc2ccc(C(=O)Nc3ccccc3N)cc2)nnc1-c1ccncc1
InChIKey: WLXGJQWKDBCQOO-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human full-length recombinant HDAC3 preincubated for 5 mins followed by HDAC substrate addition and further incubated for 45 mins by fluorescence microplate reader assay
Measurement: IC50 = 71080 nM (pChEMBL 4.150000095367432)
Descriptors: MW 416.51, ALogP 4, HBA 7, HBD 2, PSA 98.72, QED 0.36
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccc(CNC(=O)c5ccc(C(C)(C)C)cc5)c(F)c4)ccnc3[nH]2)cn1
InChIKey: IWPTYZQLDWQHRK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 482.56, ALogP 5.39, HBA 5, HBD 2, PSA 88.49, QED 0.35
Compound (SMILES): N[C@H](CC(=O)O)Cn1nnc(-c2ccc(Oc3nc4ccccc4s3)cc2)n1
InChIKey: WOCAXANSPDAXAZ-GFCCVEGCSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Displacement of [3H]WIN35428 from recombinant human dopamine transporter by radioligand binding assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 396.43, ALogP 2.54, HBA 9, HBD 2, PSA 129.04, QED 0.49
Compound (SMILES): COc1ccc2c3c([nH]c2c1)[C@H](CC(C)C)N1C[C@H](CCC(=O)OC(C)(C)C)NC(=O)[C@@H]1C3
InChIKey: YFJZAFDYUVYHMH-SSKFGXFMSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 455.6, ALogP 4.11, HBA 5, HBD 2, PSA 83.66, QED 0.64
Compound (SMILES): Cc1n[nH]c2ncc(-c3cc(N[C@@H](CO)c4ccccc4)cnc3Cl)cc12
InChIKey: VSIAIRQSYURWTI-SFHVURJKSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Inhibition of CDK4 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 379.85, ALogP 4.13, HBA 5, HBD 3, PSA 86.72, QED 0.45
Compound (SMILES): CCCCc1[nH]c(=O)c(-c2nnc(Cc3ccccc3Cl)o2)c(O)c1-c1c(OC)cccc1OC
InChIKey: AVIGKSFGMUYBAV-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JHG3
Assay: Agonist activity at rat APJ receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 1 hr by TR-FRET assay
Measurement: EC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 495.96, ALogP 5.4, HBA 7, HBD 2, PSA 110.47, QED 0.32
Compound (SMILES): COc1ccc(CNC2CC23CCc2ccccc23)c(Cl)c1OC
InChIKey: OSDYMFLVMKNLNC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells by fluorescence method
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 343.85, ALogP 4.1, HBA 3, HBD 1, PSA 30.49, QED 0.89
Compound (SMILES): O=C(O)c1ccc(-c2ccnc(Nc3ccccc3)n2)cc1C1CCCC1
InChIKey: GZYIVQMHOULGOR-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N5S9
Assay: Inhibition of human CAMKK1 using CAMKKtide as substrate assessed as residual activity by [gamma-33P]-ATP assay relative to control
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 359.43, ALogP 5.24, HBA 4, HBD 2, PSA 75.11, QED 0.65
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccc(CNC(=O)c5cc(C(C)(C)C)no5)c(F)c4)ccnc3[nH]2)cn1
InChIKey: GUHXRVDXLVSTPU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin)
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 473.51, ALogP 4.38, HBA 7, HBD 2, PSA 114.52, QED 0.39
Compound (SMILES): Cc1cccc(-c2cnc(NC3CCN(CCCN)CC3)c3[nH]c(=O)c(C)cc23)c1
InChIKey: UHIMQYINBSDFQT-UHFFFAOYSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Inhibition of ATAD2 (unknown origin) by TR-FRET assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 405.55, ALogP 3.43, HBA 5, HBD 3, PSA 87.04, QED 0.58