lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)C(c2ccc(F)c(CC(=O)N(CCO)CCC(C)C)c2)NC(=O)N1
InChIKey: UUWDCNHWTSARQA-UHFFFAOYSA-N
Target: Rhodopsin kinase GRK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15835
Assay: Inhibition of GRK1 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 536.61, ALogP 3.38, HBA 5, HBD 5, PSA 139.45, QED 0.27
Compound (SMILES): CN(C)Cc1ccccc1Nc1cc(CNCCN2CCCCC2)cc(CNCCN2CCCCC2)c1
InChIKey: NBHCATAVFSIWHT-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Modulation of human wild-type APP695 expressed in SH-SY5Y cells assessed as inhibition of amyloid beta (1 to 42 residues) production measured after 24 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 506.78, ALogP 4.64, HBA 6, HBD 3, PSA 45.81, QED 0.32
Compound (SMILES): CCCCCCCN1CCC(c2cccc(O)c2)C1
InChIKey: OLIUQFBIXLONDP-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human dopamine D2 receptor expressed in stable fibroblasts membranes by radioligand binding assay
Measurement: Ki = 369 nM (pChEMBL 6.429999828338623)
Descriptors: MW 261.41, ALogP 4.15, HBA 2, HBD 1, PSA 23.47, QED 0.75
Compound (SMILES): CN(C)C[C@]1(c2ccc(Cl)c(Cl)c2)CC[C@@](C)(O)CC1
InChIKey: BLESHHZNRPCXQQ-IYBDPMFKSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding affinity to NET (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 316.27, ALogP 4.12, HBA 2, HBD 1, PSA 23.47, QED 0.91
Compound (SMILES): CCn1c(=O)n(CC2CC2)c(=O)c2cc(NC(=O)CC(C)CC(=O)Nc3ccc(C#N)c(Cl)c3)ccc21
InChIKey: QSYGMBZUGQNPSN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat (unknown origin) expressed in human Jurkat cells assessed as inhibition of transcriptional activity after overnight incubation by human IL-17 ROR response element driven-bright-glo luciferase reporter gene assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 522.01, ALogP 4.11, HBA 7, HBD 2, PSA 125.99, QED 0.44
Compound (SMILES): CC(=O)N1c2ccc(-c3ccc(C(=O)NCCOCCOCCOCCOCC(=O)N[C@H](C(=O)N4C[C@H](O)C[C@H]4C(=O)NCc4ccc(-c5scnc5C)cc4)C(C)(C)C)cc3)cc2[C@H](Nc2ccc(Cl)cc2)C[C@@H]1C
InChIKey: UHWNJFZTYJNBAN-HYXXSBGTSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15369
Assay: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay
Measurement: Kd = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 1080.75
Compound (SMILES): CC1(C)Cc2c(c(C(=O)Nc3cc(C(F)F)ccc3F)cc3nc(Nc4c(F)cccc4Cl)[nH]c23)O1
InChIKey: PTRJVNVXIRTZMS-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES1 in human A549 cells assessed as reduction in IL-1beta-induced PGE2 production preincubated for 30 mins followed by incubation with IL-1beta for 16 to 20 hrs measured after 10 mins by HTRF assay
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 518.9, ALogP 7.14, HBA 4, HBD 3, PSA 79.04, QED 0.25
Compound (SMILES): Cc1sc(-c2ccc(C(=O)O)cc2)nc1-c1ccccc1
InChIKey: ASPYFAJZIQOSKV-UHFFFAOYSA-N
Target: Retinoic acid receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P10826
Assay: Transactivation of GST-tagged RARbeta LBD (unknown origin) assessed as fluorescein-labelled coactivator peptide recruitment measured after 4 hrs by TR-FRET analysis
Measurement: EC50 = 77.8 nM (pChEMBL 7.110000133514404)
Descriptors: MW 295.36, ALogP 4.48, HBA 3, HBD 1, PSA 50.19, QED 0.77
Compound (SMILES): Nc1nc(-c2cccc(C(F)(F)F)c2)c(C(=O)c2ccccc2Br)s1
InChIKey: KSAFJYONAATXPX-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORgamma LBD (265 to 518 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 427.25, ALogP 5.4, HBA 4, HBD 1, PSA 55.98, QED 0.57
Compound (SMILES): CC(=O)Nc1ccccc1-c1cccc2c1[nH]c1ccccc12
InChIKey: LDPDVNYCIOHPGF-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Binding affinity to PARP14 MD2 (A994 to N1191 residues) (unknown origin) expressed in bacterial expression system by ITC assay
Measurement: Kd = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 300.36, ALogP 4.95, HBA 1, HBD 2, PSA 44.89, QED 0.54
Compound (SMILES): CS(=O)(=O)c1cc(F)cc2c1c(Sc1ccc(C(F)(F)F)cc1)c1n2CC[C@@H]1CC(=O)O
InChIKey: BEQASZAURDGDEF-LLVKDONJSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of PDE2 (unknown origin)
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 487.5, ALogP 5.32, HBA 5, HBD 1, PSA 76.37, QED 0.49
Compound (SMILES): COc1c(OCCOCCOCCOCCOCCOCCOc2cccc(C(=O)C3CCN(CCc4ccc(F)cc4)CC3)c2OC)cccc1C(=O)C1CCN(CCc2ccc(F)cc2)CC1
InChIKey: OFGNHNABYOVOQY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human recombinant 5-HT2A receptor expressed in CHOK1 cells assessed as inhibition of serotonin-induced calcium release preincubated for 15 mins followed by 5-HT addition measured every 1.7 secs for 60 secs by calcium 4 dye-based FLIPR assay
Measurement: IC50 = 39.8 nM (pChEMBL 7.400000095367432)
Descriptors: MW 961.15, ALogP 7.8, HBA 13, HBD 0, PSA 123.69, QED 0.03
Compound (SMILES): Cc1cccc(Cl)c1Nc1nc2cc(C(=O)Nc3cc(C(F)F)ccc3F)c3c(c2[nH]1)CC(C)(C)O3
InChIKey: BINMTHFSOVKPHG-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES1 in human whole blood assessed as reduction in LPS-induced PGE2 production measured after 20 to 24 hrs
Measurement: IC50 = 162 nM (pChEMBL 6.789999961853027)
Descriptors: MW 514.94, ALogP 7.31, HBA 4, HBD 3, PSA 79.04, QED 0.26
Compound (SMILES): CCc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(OCC3CCOCC3)c([S@](C)(=N)=O)c2)cc1
InChIKey: OZSLLZRELNMFLA-MGBGTMOVSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgamma in human CD4+ T cells assessed as inhibition of antiCD-28 antibody stimulated IL-17A production after 4 days by HTRF method
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 508.71, ALogP 4.94, HBA 6, HBD 1, PSA 96.76, QED 0.49
Compound (SMILES): CCN(CC)C(=S)SSc1ccccc1
InChIKey: JAAVBTJKIDQEPN-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 RdRp
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 257.45, ALogP 4.05, HBA 3, HBD 0, PSA 3.24, QED 0.59
Compound (SMILES): CCn1c2ccccc2c2cc(N(C)C(=O)CC(C)CC(=O)N(C)c3ccc(C#N)cc3)ccc21
InChIKey: XGLPWVSUCGWJSP-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of BODIPY-labeled-(R)-N-(2-(3,5-difluoro-4-(trimethylsilyl)phenylamino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-(2-((1-(difluoroboryl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-2H-pyrrol-5-yl)pentanamide from human His-tagged RORgammat after 20 mins by TR-FRET assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 466.59, ALogP 5.73, HBA 4, HBD 0, PSA 69.34, QED 0.35
Compound (SMILES): O=C(CCCCCNC(=O)c1cc(-c2ccc(F)cc2)[nH]n1)NO
InChIKey: YLGBRUQGBLZQNQ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length recombinant human C-terminal His-tagged HDAC2 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 334.35, ALogP 2.01, HBA 4, HBD 4, PSA 107.11, QED 0.34
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@@H]1CCN(S(=O)(=O)c2ccccc2)C1
InChIKey: HVAKTXFDECKBOC-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human JAK1 (866-end residues) in presence of ATP
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 357.44, ALogP 1.86, HBA 5, HBD 1, PSA 82.19, QED 0.77
Compound (SMILES): C=CC(=O)Nc1cccc(NC(=O)Nc2ccnc(Nc3ccc(C4CCN(C)CC4)cc3OC)n2)c1
InChIKey: BEVNNPWOPWBYBX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR L858R/T790M mutant cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using tyrosine04 peptide as substrate after 60 mins in presence of ATP by Z-LYTE assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 501.59, ALogP 4.81, HBA 7, HBD 4, PSA 120.51, QED 0.33
Compound (SMILES): Cc1cn2c(-c3cn[nH]c3)cnc2c(Nc2cc(C(c3ccccn3)N3CCCC3)ns2)n1
InChIKey: CWAYHIGLCQXMLX-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using Tamra-PKAtide as substrate by fluorescence polarization assay
Measurement: IC50 < 4 nM (pChEMBL 8.39799976348877)
Descriptors: MW 457.57, ALogP 4.21, HBA 9, HBD 2, PSA 99.92, QED 0.39
Compound (SMILES): CCOC(=O)N[C@@H]1CCC2[C@@H](C1)C[C@H]1C(=O)O[C@H](C)[C@H]1[C@H]2/C=C/c1ccc(-c2cccc(F)c2)cn1
InChIKey: ZBGXUVOIWDMMJE-ICAXAWPRSA-N
Target: Proteinase-activated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25116
Assay: Antagonist activity at PAR1 in human EAhy926 cells assessed as inhibition of TFLLRN-NH2-induced intracellular calcium mobilization pretreated for 15 mins followed by TFLLRN-NH2 addition measured at 5 secs interval for 250 secs by Fluo-4/AM dye based fluorescence assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 492.59, ALogP 5.63, HBA 5, HBD 1, PSA 77.52, QED 0.55
Compound (SMILES): CC(=O)N[C@@H](C)/C=C/c1cnc(Oc2ccc(OCC3CC3)cc2Cl)nc1
InChIKey: JJGDHXUPNZBDTE-OOPCZODUSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of recombinant human ACC1 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.87, ALogP 4.25, HBA 5, HBD 1, PSA 73.34, QED 0.73
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCCC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)CN(C)C(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C(C)C)C(=O)O
InChIKey: GRHVYJSEPXGXNX-DDNPPLFWSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Agonist activity at human GCG receptor expressed in HEK293 cells assessed as increase in cAMP level after 5 hrs by CRE driven luciferase reporter gene assay
Measurement: EC50 = 0.016 nM (pChEMBL 10.800000190734863)
Descriptors: MW 3738.22
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(CNCCN(C(C)C)C(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: OTOQHEDNDUXMDP-SXVKIKQOSA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Binding affinity to CA-SP1 P373S/V370A double mutant in HIV-1 subtype B NL4-3 infected in human MT2 cells assessed as inhibition of viral maturation by measuring virus yield after 4 to 5 days in presence of 10% FBS by luciferase reporter gene assay
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 671.07, ALogP 10.74, HBA 3, HBD 2, PSA 52.57, QED 0.19
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@@H]1CCN(C(=O)Nc2ccccc2)C1
InChIKey: NHQRSMMVOOCIHH-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human JAK1 (866-end residues) in presence of ATP
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 336.4, ALogP 2.7, HBA 4, HBD 2, PSA 77.15, QED 0.77
Compound (SMILES): COc1ccc(Sc2c(C)c3c(N)nc(N)nc3n2C)cc1
InChIKey: OKWZEJPRXOZLRD-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of human recombinant DHFR expressed in Escherichia coli Rosetta Gami B (DE3) competent cells using DHFA as substrate and NADPH
Measurement: IC50 = 1372 nM (pChEMBL 5.860000133514404)
Descriptors: MW 315.4, ALogP 2.6, HBA 7, HBD 2, PSA 91.98, QED 0.77
Compound (SMILES): C[C@]1(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)N=C(N)O[C@H](CF)[C@@H]1F
InChIKey: BFEQDIQTMANSEQ-RVKKMQEKSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SH-SY5Y cells harboring wild-type human beta-APP assessed as reduction in secreted amyloid beta (1 to 40) after 24 hrs by HTRF assay
Measurement: IC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 396.34, ALogP 2.85, HBA 5, HBD 2, PSA 89.6, QED 0.78
Compound (SMILES): COc1cc2ccc(Br)cc2cc1[C@@H](c1ccccc1)[C@@](O)(CCN(C)C)c1ccc2occc2c1
InChIKey: RKVOXGBEINNIFV-FIRIVFDPSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 544.49, ALogP 7.33, HBA 4, HBD 1, PSA 45.84, QED 0.22
Compound (SMILES): N#Cc1cccc(CS(=O)(=O)Nc2ccccc2-c2cccc3c2[nH]c2ccccc23)c1
InChIKey: OGCXSSRQUWIBMG-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Displacement of ARTK(Bio)QTARK(Aoa-RADP)S from His6-tagged PARP14 MD2 (A994 to N1191 residues) (unknown origin) expressed in bacterial expression system after 30 mins by AlphaScreen assay
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 437.52, ALogP 5.8, HBA 3, HBD 2, PSA 85.75, QED 0.36
Compound (SMILES): O=C(NO)c1ccc(Cn2nc(-c3ccc(F)cc3)cc2Cc2ccccc2)cc1
InChIKey: JOEWBFMDFCFWJV-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length recombinant human C-terminal His-tagged HDAC2 expressed in baculovirus infected sf9 cells using Boc-Lys-(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by fluorescence assay
Measurement: IC50 = 763 nM (pChEMBL 6.119999885559082)
Descriptors: MW 401.44, ALogP 4.45, HBA 4, HBD 2, PSA 67.15, QED 0.37
Compound (SMILES): CCOc1ccc(Oc2ncc(/C=C/[C@H](C)NC(C)=O)s2)cc1
InChIKey: CWVWOIDGHRSLAW-DJTWPOEFSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 332.43, ALogP 3.87, HBA 5, HBD 1, PSA 60.45, QED 0.84
Compound (SMILES): Cc1cn2c(-c3cn[nH]c3)cnc2c(Nc2cc(Cc3ncccc3C)ns2)n1
InChIKey: XFDAGNBBOZKUIP-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using Tamra-PKAtide as substrate by fluorescence polarization assay
Measurement: IC50 < 4 nM (pChEMBL 8.39799976348877)
Descriptors: MW 402.49, ALogP 3.92, HBA 8, HBD 2, PSA 96.68, QED 0.46
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]ncc3c2)C(c2ccc(F)c(CC(=O)NCc3ccc(C#N)nc3)c2)NC(=O)N1
InChIKey: OMFMIKJEJUTHJI-UHFFFAOYSA-N
Target: Rhodopsin kinase GRK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15835
Assay: Inhibition of GRK1 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 538.54, ALogP 3.09, HBA 6, HBD 5, PSA 164.69, QED 0.24
Compound (SMILES): CC(=O)N[C@@H](C)/C=C/c1ccc(Oc2cc3sc(C)nc3cc2Cl)nc1
InChIKey: YPEVGBRYJCOHDW-ZWNMCFTASA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition of recombinant human ACC1 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis
Measurement: IC50 = 52100 nM (pChEMBL 4.28000020980835)
Descriptors: MW 387.89, ALogP 4.98, HBA 5, HBD 1, PSA 64.11, QED 0.67
Compound (SMILES): CCCN1CCC(N(Cc2cccnc2)C(=O)Nc2cccc(C(F)(F)F)c2)CC1
InChIKey: MYAZRJLIDGICMI-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Inhibition of human DCN1-mediated cullin neddylation assessed as reduction in transfer of fluorescein-5-maleimide-tagged NEDD8 from N-terminally acetylated human UBE2M to CUL2-CTD measured for 10 sec by pulse-chase assay
Measurement: EC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 420.48, ALogP 5.01, HBA 3, HBD 1, PSA 48.47, QED 0.71
Compound (SMILES): CCN(CCCCCCn1sc2cc(OC)c(OC)cc2c1=O)Cc1ccccc1OC
InChIKey: GDQWCUUOQPSARQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 458.62, ALogP 5.17, HBA 7, HBD 0, PSA 52.93, QED 0.33
Compound (SMILES): CCN(CCCn1sc2cc(OC)c(OC)cc2c1=O)Cc1ccccc1OC
InChIKey: WHTNMFXSNZRZAH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 416.54, ALogP 4, HBA 7, HBD 0, PSA 52.93, QED 0.5
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCCC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)NC(C)(C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C(C)C)C(=O)O
InChIKey: LWXXVXDDINPHFC-TZJYYITESA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Agonist activity at human GCG receptor expressed in HEK293 cells assessed as increase in cAMP level after 5 hrs by CRE driven luciferase reporter gene assay
Measurement: EC50 = 0.028 nM (pChEMBL 10.550000190734863)
Descriptors: MW 3726.28
Compound (SMILES): CC(C)Oc1c2c(c(OC(C)C)c3ccccc13)C(=O)N(c1ccc(CC(=O)O)cc1)C2
InChIKey: HEIGNXONEPFJJA-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Displacement of [3H]PGE2 from human EP4 receptor expressed in HEK 293 (EBNA) cell membranes incubated for 60 mins by scintillation counting method
Measurement: Ki = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 433.5, ALogP 5.2, HBA 4, HBD 1, PSA 76.07, QED 0.55
Compound (SMILES): Cc1cccc(Cl)c1Nc1nc2cc(C(=O)Nc3ccc(F)c(C(F)(F)F)c3)c3c(c2[nH]1)CC(C)(C)O3
InChIKey: NMAXOPDWQJADOX-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES1 in human A549 cells assessed as reduction in IL-1beta-induced PGE2 production preincubated for 30 mins followed by incubation with IL-1beta for 16 to 20 hrs measured after 10 mins by HTRF assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 532.93, ALogP 7.39, HBA 4, HBD 3, PSA 79.04, QED 0.24
Compound (SMILES): CN1CCN(Cc2ccccc2-c2cc(CNCCN3CCCCC3)cc(CNCCN3CCCCC3)c2)CC1
InChIKey: DCQYOHBWMMOZCH-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Modulation of human wild-type APP695 expressed in SH-SY5Y cells assessed as inhibition of amyloid beta (1 to 42 residues) production measured after 24 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 546.85, ALogP 4.25, HBA 6, HBD 2, PSA 37.02, QED 0.37
Compound (SMILES): CC1(C)Cc2c(c(C(=O)Nc3cc(C4CC4)ccc3F)cc3nc(Nc4c(Cl)cccc4Cl)[nH]c23)O1
InChIKey: NVDCVEDDKFLWJM-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES1 in human A549 cells assessed as reduction in IL-1beta-induced PGE2 production preincubated for 30 mins followed by incubation with IL-1beta for 16 to 20 hrs measured after 10 mins by HTRF assay
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 525.41, ALogP 7.6, HBA 4, HBD 3, PSA 79.04, QED 0.25
Compound (SMILES): CCOc1ccc(S(C)(=O)=O)cc1-c1cn(C)c(=O)c2ccc(-c3cnn(C)c3)cc12
InChIKey: VINFIMKBSZJKES-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged human BRD4-BD1 using H4K5acK8acK12acK16ac as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 437.52, ALogP 3.41, HBA 7, HBD 0, PSA 83.19, QED 0.48
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(CNCCCO)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: MMLZLJBCUYDPKZ-YQUHGRJISA-N
Target: Gag-Pol polyprotein (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)(HIV-1)
UniProt: P04585
Assay: Binding affinity to CA-SP1 P373S/V370A double mutant in HIV-1 subtype B NL4-3 infected in human MT2 cells assessed as inhibition of viral maturation by measuring virus yield after 4 to 5 days in presence of 10% FBS by luciferase reporter gene assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 601.92, ALogP 9.01, HBA 3, HBD 3, PSA 69.56, QED 0.21
Compound (SMILES): Cc1cccc(Cl)c1Nc1nc2cc(C(=O)Nc3cc(C(F)(F)F)ccc3F)c3c(c2[nH]1)CC(C)(C)O3
InChIKey: NEDYVEZMEJJRFC-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES1 in human A549 cells assessed as reduction in IL-1beta-induced PGE2 production preincubated for 30 mins followed by incubation with IL-1beta for 16 to 20 hrs measured after 10 mins by HTRF assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 532.93, ALogP 7.39, HBA 4, HBD 3, PSA 79.04, QED 0.24
Compound (SMILES): COCCOc1cc(CC2CCN(CCc3ccc4c(c3)CCCO4)CC2)ccc1Br
InChIKey: FMQPPLSPODBXRQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor expressed in CHOK1 cell membranes after 30 mins by liquid scintillation counting
Measurement: Ki = 43.1 nM (pChEMBL 7.369999885559082)
Descriptors: MW 488.47, ALogP 5.3, HBA 4, HBD 0, PSA 30.93, QED 0.45
Compound (SMILES): CCC1(O)CCCN(C(=O)CCc2cc(C3NC(=O)NC(C)=C3C(=O)Nc3ccc4[nH]ncc4c3)ccc2F)C1
InChIKey: FQDQVLRANQNTFE-UHFFFAOYSA-N
Target: Rhodopsin kinase GRK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15835
Assay: Inhibition of GRK1 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 548.62, ALogP 3.66, HBA 5, HBD 5, PSA 139.45, QED 0.31
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2-c2ccc(F)cc2)c1
InChIKey: MYIZAYXMTDPUHW-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of recombinant human N-terminal His-FLAG tagged JARID1B (2 to 751 residues) expressed in baculovirus infected sf9 cells using H3K4me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 283.26, ALogP 2.77, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): C=CC(=O)Nc1cccc(NC(=O)Nc2nc(Nc3ccc(N4CCC(N5CCOCC5)CC4)cc3OC)ncc2Cl)c1
InChIKey: GOKFAZOSPCHSOH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR L858R/T790M mutant cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using tyrosine04 peptide as substrate after 60 mins in presence of ATP by Z-LYTE assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 607.12, ALogP 4.95, HBA 9, HBD 4, PSA 132.98, QED 0.25
Compound (SMILES): Cn1cc(-c2ncco2)c2ccccc2c1=O
InChIKey: VYVPGIUGYNRIJA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: In Vitro Enzyme Inhibition Assay: Determination of the IC50 for the heterocyclic derivative BRD4 inhibitors disclosed herein was performed as follows. His-tagged BRD4 was cloned, expressed and purified to homogeneity. Filipakopoulos et al., Nature 468:1067 (2010). BRD4 binding and inhibition was assessed by monitoring the interaction of biotinylated H4-tetraacetyl peptide (AnaSpec, H4K5/8/12/16(Ac), biotin-labeled) with the target using the AlphaScreen technology (Life Technologies). In a 384-well ProxiPlate BRD4(BD1) (2 nM final) was combined with peptide (15 nM final) in 50 mM HEPES (pH 7.3), 10 mM NaCl, 0.25 mM TCEP, 0.1% (w/v) BSA, and 0.005% (w/v) Brij-35 either in the presence of DMSO (final 0.4% DMSO) or compound dilution series in DMSO. After 20 min incubation at room temp, Alpha streptavidin donor beads and Nickel Chelate acceptor beads were added to a final concentration of 5 μg/mL. After 2 hr of equilibration, plates were read on an Envision instrument and the IC50 was calculated using a four parameter non-linear curve fit. Chemistry Example 1 (2-methyl-4-phenylisoquinolin-1-one) had an IC50 of 2.782 μM in this assay format.
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 226.24, ALogP 2.19, HBA 4, HBD 0, PSA 48.03, QED 0.64
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1cc(NCCN2CCOCC2)nc(Nc2ccc(C#N)cc2)c1
InChIKey: QKLTYLWGJQRQIN-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase K103N/Y181C double mutant using poly (A)/oligo (dT)15 as template/primer assessed as decrease in biotin-dUTP incorporation after 1 hr by ELISA
Measurement: IC50 = 6270 nM (pChEMBL 5.199999809265137)
Descriptors: MW 494.6, ALogP 5.39, HBA 8, HBD 2, PSA 106.23, QED 0.38
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCNC(=O)C[C@@H]2N=C(c3ccc(Cl)cc3)c3c(sc(C)c3C)-n3c(C)nnc32)C(C)(C)C)cc1
InChIKey: PTAMRJLIOCHJMQ-PYNGZGNASA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15369
Assay: Binding affinity to N-terminal His6-tagged recombinant human VHL (54 to 213 residues)/elongin C (17 to 112 residues)/elongin B (1 to 104 residues) expressed in Escherichia coli BL21 (DE3) assessed as compound binary complex formation by isothermal titration calorimetry-based assay
Measurement: Kd = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 1002.66
Compound (SMILES): N#CCC(=O)N1CC[C@@H](N(CC2CC2)c2ncnc3[nH]ccc23)C1
InChIKey: OZUOJLAXJHHURA-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human JAK1 (866-end residues) in presence of ATP
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 324.39, ALogP 1.69, HBA 5, HBD 1, PSA 88.91, QED 0.9
Compound (SMILES): CCCCCCCCCCCC(=O)OCC(=O)NCc1ccc(O)c(OC)c1
InChIKey: XJQPEXQHOOCRNS-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: O35433
Assay: Agonist activity at rat TRPV1 expressed in human SH-SY5Y cells assessed as intracellular calcium accumulation by Fluo-4 NW dye based fluorescence assay
Measurement: EC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 393.52, ALogP 4.48, HBA 5, HBD 2, PSA 84.86, QED 0.34
Compound (SMILES): CC(CC(=O)Nc1ccc(C#N)cc1)CC(=O)Nc1ccc2[nH]c3c(c2c1)CCCC3
InChIKey: VJKYAYGALXPDNN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of BODIPY-labeled-(R)-N-(2-(3,5-difluoro-4-(trimethylsilyl)phenylamino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-(2-((1-(difluoroboryl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-2H-pyrrol-5-yl)pentanamide from human His-tagged RORgammat after 20 mins by TR-FRET assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 414.51, ALogP 4.91, HBA 3, HBD 3, PSA 97.78, QED 0.53
Compound (SMILES): CC(C)OC(=O)N1CCC2(CC1)CC(CCCOc1ccc(C(=O)N3CC(O)C3)c(F)c1)C2
InChIKey: DIQYIQPVBFHDBJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 462.56, ALogP 3.84, HBA 5, HBD 1, PSA 79.31, QED 0.62
Compound (SMILES): CNC[C@]1(c2ccc(Cl)c(Cl)c2)CC[C@](C)(O)CC1
InChIKey: IEEXXKGDHWBIJX-SHTZXODSSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of DAT (unknown origin)-mediated uptake
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 302.25, ALogP 3.78, HBA 2, HBD 2, PSA 32.26, QED 0.89
Compound (SMILES): CN1CCN(Cc2ccccc2-c2cc(C(=O)NCCN3CCCCC3)cc(C(=O)NCCN3CCCCC3)c2)CC1
InChIKey: TXHWRTFCAGUONB-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Modulation of human wild-type APP695 expressed in SH-SY5Y cells assessed as inhibition of amyloid beta (1 to 42 residues) production measured after 24 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 574.81, ALogP 3.53, HBA 6, HBD 2, PSA 71.16, QED 0.43
Compound (SMILES): COCCOc1cc(Br)cc(CC2CCN(CCc3cc4c(cc3Cl)OCCO4)CC2)c1
InChIKey: JPXOLXCDNZUCCQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor expressed in CHOK1 cell membranes after 30 mins by liquid scintillation counting
Measurement: Ki = 546 nM (pChEMBL 6.260000228881836)
Descriptors: MW 524.88, ALogP 5.4, HBA 5, HBD 0, PSA 40.16, QED 0.41
Compound (SMILES): COc1cc(CNC(=O)COC(=O)/C=C(\C)CCC=C(C)C)c(I)cc1O
InChIKey: UQTPQYVSYSETPZ-RIYZIHGNSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at TRPV1 (unknown origin) expressed in human SH-SY5Y cells assessed as inhibition of capsaicin-induced calcium increase after 25 mins by Fluo-4 NW dye-based fluorescence assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 487.33, ALogP 3.86, HBA 5, HBD 2, PSA 84.86, QED 0.24
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: BLSKCYKLXHEUHH-BYPGACHISA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Agonist activity at human GCG receptor expressed in HEK293 cells assessed as increase in cAMP level after 5 hrs by CRE driven luciferase reporter gene assay
Measurement: EC50 = 0.031 nM (pChEMBL 10.510000228881836)
Descriptors: MW 3381.73
Compound (SMILES): O=[N+]([O-])c1ccc(O)c(CN2CCOCC2)c1
InChIKey: FHQJAMUJPVTFPX-UHFFFAOYSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Non-competitive inhibition of recombinant human cathepsin B exopeptidase activity assessed as inhibitory constant for enzyme-substrate-inhibitor complex using Abz-Gly-Ile-Val-Arg-Ala-Lys(Dnp)-OH as substrate in presence of pH 5 acetate buffer by fluorescence assay
Measurement: Ki = 97000 nM (pChEMBL 4.010000228881836)
Descriptors: MW 238.24, ALogP 1.13, HBA 5, HBD 1, PSA 75.84, QED 0.63
Compound (SMILES): COC(=O)Nc1ccc(-c2cc([C@H](Cc3ccccc3)NC(=O)/C=C/c3cc(Cl)ccc3-n3cnnn3)nnc2C)cc1
InChIKey: ARGAWPOUZMCKAP-ZOYLIWTNSA-N
Target: Coagulation factor VII (SINGLE PROTEIN), Homo sapiens
UniProt: P08709
Assay: Inhibition of human factor 7a
Measurement: Ki > 13300 nM (pChEMBL 4.875999927520752)
Descriptors: MW 595.06, ALogP 5.37, HBA 9, HBD 2, PSA 136.81, QED 0.22
Compound (SMILES): CN(C)Cc1ccccc1-c1cc(C(=O)NCCN2CCCCC2)cc(C(=O)NCCN2CCCCC2)c1
InChIKey: YSKOGCAZGBZVKS-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Modulation of human wild-type APP695 expressed in SH-SY5Y cells assessed as inhibition of amyloid beta (1 to 42 residues) production measured after 24 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 519.73, ALogP 3.85, HBA 5, HBD 2, PSA 67.92, QED 0.47
Compound (SMILES): Nc1nc(-c2cc(Br)cc(C(F)(F)F)c2)c(C(=O)c2ccccc2Cl)s1
InChIKey: DWEDZWSSQACUGB-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORgamma LBD (265 to 518 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 461.69, ALogP 6.06, HBA 4, HBD 1, PSA 55.98, QED 0.48
Compound (SMILES): C=CC(=O)Nc1cccc(NC(=O)C(C)(C)c2ccnc(Nc3ccc(N4CCN(C)CC4)cc3OC)n2)c1
InChIKey: QDPDFAMDCIUMLZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR L858R/T790M mutant cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using tyrosine04 peptide as substrate after 60 mins in presence of ATP by Z-LYTE assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 529.65, ALogP 4.02, HBA 8, HBD 3, PSA 111.72, QED 0.36
Compound (SMILES): Cc1ccnc(Cc2cc(Nc3nc(C)cn4c(-c5cn[nH]c5)cnc34)sn2)c1
InChIKey: YRBTWWVMRDALFA-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using Tamra-PKAtide as substrate by fluorescence polarization assay
Measurement: IC50 < 4 nM (pChEMBL 8.39799976348877)
Descriptors: MW 402.49, ALogP 3.92, HBA 8, HBD 2, PSA 96.68, QED 0.46
Compound (SMILES): CN(C)CCCOc1ccc(CN(C)c2nc3ccc(Oc4ccc(C(F)(F)F)cc4)cc3s2)cc1.O=C(O)C(F)(F)F
InChIKey: XUYPNSGJENHGKL-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of recombinant human Cav3.2-alpha1 expressed in HEK293T cells assessed as decrease in KCl-induced calcium mobilization measured after 600 secs post compound addition and 300 secs post KCl addition by calcium 4 dye-based FLIPR assay
Measurement: IC50 = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 515.6, ALogP 7.07, HBA 6, HBD 0, PSA 37.83, QED 0.21
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3ncc4nc(Sc5ccccc5)n(C5CCOCC5)c4n3)cc2)CC1
InChIKey: XPDCETIJRALGKS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant (unknown origin) using poly (Glu, Tyr) as substrate after 40 mins by kinase-glo plus luminescence assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 529.71, ALogP 5.6, HBA 9, HBD 1, PSA 71.34, QED 0.33
Compound (SMILES): Cn1cc(-c2cccc(NS(C)(=O)=O)c2)c2ccccc2c1=O
InChIKey: ZYMKOUADMCSPLV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged human BRD4-BD1 using H4K5acK8acK12acK16ac as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 328.39, ALogP 2.58, HBA 4, HBD 1, PSA 68.17, QED 0.8
Compound (SMILES): O=C(NCCN1CCCCC1)c1cc(Nc2ccccc2CN2CCOCC2)cc(C(=O)NCCN2CCCCC2)c1
InChIKey: QIHBXRCCDUYUDA-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Modulation of human wild-type APP695 expressed in SH-SY5Y cells assessed as inhibition of amyloid beta (1 to 42 residues) production measured after 24 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.79, ALogP 3.69, HBA 7, HBD 3, PSA 89.18, QED 0.36
Compound (SMILES): COc1cc2ccc(Br)cc2cc1[C@@H](c1ccnc(OC)c1OC)[C@@](O)(CCN(C)C)c1cc2ccccc2o1
InChIKey: KJLREUWSBLTSCB-QLWXXVCSSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 605.53, ALogP 6.74, HBA 7, HBD 1, PSA 77.19, QED 0.19
Compound (SMILES): CCc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(N3CCN(C(C)=O)CC3)c(S(C)(=N)=O)c2)cc1
InChIKey: VEBXJKRFJNECJQ-UHFFFAOYSA-N
Target: Interleukin-17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q16552
Assay: I L-17A Secretion: This model allows measurement of the effect of inhibitors on IL-17A secretion by CD4+ cells. The cells are frozen CD4+ cells (STEMCELL, #70026), isolated from peripheral human blood and activated with anti-CD3 and anti-CD28 antibodies. The amount of IL-17a secreted is measured by the TR-FRET (kit HTRF® Human Interleukin 17A (Cisbio, #64H17PEC)) technology.The cells are rapidly thawed, resuspended in their culture medium (RPMI inactivated 10% FCS) supplemented with soluble anti-CD28 antibodies and seeded (100 000 cells/well) in 96-well plates precoated with anti-CD3 antibodies. The cells are then treated with the ranges of inhibitors to be tested (from 1000 nM to 0.05 nM, 0.1% DMSO). After 4 days of incubation, the HTRF signal is measured using a microplate reader (λexcitation=337 nm, λemission=620/665 nm). The ratios obtained (665/620) are normalized relative to the positive control (cells activated with anti-CD3 and anti-CD28, 0.1% DMSO). The IC50 values are calculated from a 4-parameter logistic model using the XLFit software (IDBS).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 520.72, ALogP 3.8, HBA 6, HBD 1, PSA 101.85, QED 0.57
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@H](O)CN2C(=O)[C@@H](NC(=O)COCCCOCCCCOCCCOc2ccc(Nc3ncc(Br)c(NCCCN(C)C(=O)C4CCC4)n3)cc2)C(C)(C)C)cc1
InChIKey: QMGHHBHPDDAGGO-JTTRWUFTSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Binding affinity to human full length wild-type TBK1 expressed in mammalian expression system
Measurement: Kd = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 1093.2
Compound (SMILES): Cn1ccnc1-c1cn(C)c(=O)c2ccccc12
InChIKey: ZPWMDBQBODQPTF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: In Vitro Enzyme Inhibition Assay: Determination of the IC50 for the heterocyclic derivative BRD4 inhibitors disclosed herein was performed as follows. His-tagged BRD4 was cloned, expressed and purified to homogeneity. Filipakopoulos et al., Nature 468:1067 (2010). BRD4 binding and inhibition was assessed by monitoring the interaction of biotinylated H4-tetraacetyl peptide (AnaSpec, H4K5/8/12/16(Ac), biotin-labeled) with the target using the AlphaScreen technology (Life Technologies). In a 384-well ProxiPlate BRD4(BD1) (2 nM final) was combined with peptide (15 nM final) in 50 mM HEPES (pH 7.3), 10 mM NaCl, 0.25 mM TCEP, 0.1% (w/v) BSA, and 0.005% (w/v) Brij-35 either in the presence of DMSO (final 0.4% DMSO) or compound dilution series in DMSO. After 20 min incubation at room temp, Alpha streptavidin donor beads and Nickel Chelate acceptor beads were added to a final concentration of 5 μg/mL. After 2 hr of equilibration, plates were read on an Envision instrument and the IC50 was calculated using a four parameter non-linear curve fit. Chemistry Example 1 (2-methyl-4-phenylisoquinolin-1-one) had an IC50 of 2.782 μM in this assay format.
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 239.28, ALogP 1.94, HBA 4, HBD 0, PSA 39.82, QED 0.65
Compound (SMILES): C=CC(=O)Nc1cccc(NC(=O)Nc2ccnc(Nc3ccc(N4CCOCC4)cc3OC)n2)c1
InChIKey: MPRSBSDBHFWKDM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human GST-tagged EGFR L858R/T790M mutant cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using tyrosine04 peptide as substrate after 60 mins in presence of ATP by Z-LYTE assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 489.54, ALogP 3.83, HBA 8, HBD 4, PSA 129.74, QED 0.35
Compound (SMILES): Cc1cn2c(-c3cn[nH]c3)cnc2c(Nc2cc(Cc3cccc(C(=O)N4CCCCC4)n3)ns2)n1
InChIKey: BLSODUBGWXTNGZ-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using Tamra-PKAtide as substrate by fluorescence polarization assay
Measurement: IC50 < 4 nM (pChEMBL 8.39799976348877)
Descriptors: MW 499.6, ALogP 4.24, HBA 9, HBD 2, PSA 116.99, QED 0.36
Compound (SMILES): N#Cc1ccccc1CN1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1
InChIKey: PEDPHRFSEZDVTK-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 expressed in CHOK1 cell membranes
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 540.46, ALogP 5.98, HBA 7, HBD 0, PSA 73.87, QED 0.27
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1cc(NCCN2CCNCC2)nc(Nc2ccc(C#N)cc2)n1
InChIKey: MVFPJNHSTSIHDC-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase K103N/Y181C double mutant using poly (A)/oligo (dT)15 as template/primer assessed as decrease in biotin-dUTP incorporation after 1 hr by ELISA
Measurement: IC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 494.6, ALogP 4.35, HBA 9, HBD 3, PSA 121.92, QED 0.37
Compound (SMILES): COC[C@H]1[C@@H](c2ccc(Cl)c(Cl)c2)C[C@@H]2CC[C@H]1N2C
InChIKey: PGYDXVBZYKQYCS-RSUWNVLCSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Binding affinity to NET (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 314.26, ALogP 4.21, HBA 2, HBD 0, PSA 12.47, QED 0.83
Compound (SMILES): CCOc1c2c(c(OCC)c3ccccc13)C(=O)N(c1ccc(C(C)C(=O)O)cc1)C2
InChIKey: VRKBVSUBBJLUGY-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Displacement of [3H]PGE2 from human EP4 receptor expressed in HEK 293 (EBNA) cell membranes incubated for 60 mins by scintillation counting method
Measurement: Ki = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 419.48, ALogP 4.99, HBA 4, HBD 1, PSA 76.07, QED 0.58
Compound (SMILES): Cn1cc(-c2nn(Cc3ccc(C(=O)NC4CCCC4)cc3)c(=O)c3ccccc23)cn1
InChIKey: YKVSMJHGYWIRDE-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora B (unknown origin) using kemptide as substrate after 30 mins by kinase-Glo luminescence method
Measurement: IC50 = 265 nM (pChEMBL 6.579999923706055)
Descriptors: MW 427.51, ALogP 3.52, HBA 6, HBD 1, PSA 81.81, QED 0.53
Compound (SMILES): C[C@]1(c2cc(NC(=O)c3cnc(C(F)F)cn3)ccc2F)N=C(N)O[C@H](CF)[C@@H]1F
InChIKey: ASUXJKFZYWODQA-QWQRMKEZSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SH-SY5Y cells harboring wild-type human beta-APP assessed as reduction in secreted amyloid beta (1 to 40) after 24 hrs by HTRF assay
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 429.35, ALogP 3.04, HBA 6, HBD 2, PSA 102.49, QED 0.71
Compound (SMILES): CCc1ccc(N(CC(C)C)S(=O)(=O)c2ccc(NCC3(O)CCOCC3)c(S(C)(=N)=O)c2)cc1
InChIKey: YPTBGUKCVIWVDD-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: GAL4-RORgamma Transactivation: The RORγ transactivation model was developed from the line HG5LN, which is a HeLa line that stably expresses a luciferase reporter gene controlled by a pentamer of the GAL4 recognition domain of yeast and of a β-globin promoter. The HG5LN line was stably transfected by the DNA-binding domain (DBD) of GAL4 fused to the ROR gamma ligand-binding domain (LBD). Molecules that inhibit the ROR gamma constitutive activity reduce the luciferase expression, thus leading to a reduction in the emitted luminescence.The cells are seeded in 384-well plates (5000 cells in 45 μL/well of culture medium containing 10% fetal calf serum) and incubated for 4 hours at 37° C., 5% CO2. 5 μL of the test molecules (compounds described in the tables described above) are then added to each well and the plates are incubated for 18 hours at a temperature of 37° C. under 5% of CO2. 20 μL of luciferase substrate (Promega) are added to each well and the luminescence emitted is read by a microplate reader.The luminescence units (RLU) are normalized by positive controls (POS containing a saturated concentration of benzenesulfonamide, N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]) and negative controls (NEG containing DMSO): % inhibition=((RLU−NEG)*100)/(POS−NEG). The IC50 values are calculated from a 4-parameter logistic model using the XLFit software (IDBS).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 523.72, ALogP 4.09, HBA 7, HBD 3, PSA 119.79, QED 0.43
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(N)=O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: ORPZALWAWWEEDP-NXXUBLNKSA-N
Target: Proprotein convertase subtilisin/kexin type 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBP7
Assay: Binding affinity to human PCSK9 by surface plasmon resonance
Measurement: Kd = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 1715.88
Compound (SMILES): COc1cc2ccc(Br)cc2cc1[C@@H](c1ccnc(OC)c1OC)[C@@](O)(CCN(C)C)c1ccc2occc2c1
InChIKey: CXLLHSXYRSFUSQ-QLWXXVCSSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 605.53, ALogP 6.74, HBA 7, HBD 1, PSA 77.19, QED 0.19
Compound (SMILES): COC(=O)N[C@@H](C)/C=C/c1cnc(Oc2ccc(OC(C)C)cc2)s1
InChIKey: UWNYRXKEKHUZMJ-KADSFNECSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 362.45, ALogP 4.48, HBA 6, HBD 1, PSA 69.68, QED 0.79