lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCc1nc2c(N)nc3cc(OC)ccc3c2n1CC(C)(C)O
InChIKey: OQZJBCNCOMTKHL-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 expressed in HEK-Blue cells assessed as induction of NFkappaB activation by measuring increase in SEAP level by SEAP reporter gene-based UV-vis absorbance method
Measurement: EC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 342.44, ALogP 3.29, HBA 6, HBD 2, PSA 86.19, QED 0.72
Compound (SMILES): Cc1ncn(CC(F)F)c1-c1nnc([C@H]2CCC[C@@H](N(C)C(=O)c3cccc(C(F)(F)F)c3)C2)[nH]1
InChIKey: OGSWCIPCMCTXTK-WMLDXEAASA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 receptor expressed in HEK293 cells assessed as accumulation of inositol phosphate incubated for 1 hr followed by IP1-d2 addition by HTRF assay
Measurement: EC50 < 120 nM (pChEMBL 6.921000003814697)
Descriptors: MW 496.48, ALogP 5.06, HBA 5, HBD 1, PSA 79.7, QED 0.48
Compound (SMILES): Nc1ccc(C(=O)N2CCN(C(=O)c3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: FDVSJQWHFBHOPB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow carbon dioxide hydration assay
Measurement: Ki = 78.8 nM (pChEMBL 7.099999904632568)
Descriptors: MW 388.45, ALogP 0.51, HBA 5, HBD 2, PSA 126.8, QED 0.74
Compound (SMILES): COc1cc(N2CCC(Oc3ccc(N4N=C(C(F)(F)F)[C@@H](C)C4CC(=O)O)cc3)C(C)C2)c(Cl)cn1
InChIKey: GKIUHMMLGAMMOO-AUPDUATKSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Modulation of GPR120 (unknown origin)
Measurement: EC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 540.97, ALogP 5.26, HBA 7, HBD 1, PSA 87.49, QED 0.51
Compound (SMILES): COc1ccccc1CN1[C@@H]2CCC[C@H]1C[C@H](NC(=O)c1cc(OC)c(OC)c(OC)c1)C2
InChIKey: NKNVQTJFJKZPQJ-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 454.57, ALogP 4.04, HBA 6, HBD 1, PSA 69.26, QED 0.65
Compound (SMILES): CN(C)C1CCc2c(cccc2-c2c3ccccc3cc3ccccc23)C1
InChIKey: DBUFMYHPGGUVEP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-5-carboxamidotryptamine from human 5-HT1A receptor expressed in HEK293T cell membranes incubated for 90 mins by scintillation counting method
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 351.49, ALogP 6.08, HBA 1, HBD 0, PSA 3.24, QED 0.4
Compound (SMILES): CC[C@@](O)(c1nnn(Cc2ccc3c(-c4ccc(F)cc4)cc(C(N)=O)nc3c2)n1)C(F)(F)F
InChIKey: UZTDYJVVVFMAQX-OAQYLSRUSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Inhibition of human mGluR3 by FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.42, ALogP 3.33, HBA 7, HBD 2, PSA 119.81, QED 0.41
Compound (SMILES): COc1cc2c(cc1OC)C([C@@H](C)c1ccc(OC)c(OC)c1O)=NCC2
InChIKey: MRIXQJHQZAJICE-LBPRGKRZSA-N
Target: Cocaine esterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00748
Assay: Inhibition of human CE2 using fluorescein diacetate as substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins by luminescence assay
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 371.43, ALogP 3.58, HBA 6, HBD 1, PSA 69.51, QED 0.84
Compound (SMILES): CN[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: AGBBPVCMSXHJNT-CMOCDZPBSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H]UR-KK200 from human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ measured after 90 mins by scintillation counting analysis
Measurement: Ki = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 619.77, ALogP -1.96, HBA 8, HBD 12, PSA 286.45, QED 0.04
Compound (SMILES): O=C1c2ccccc2C(=O)c2c1nnn2-c1ccc(Cl)nc1
InChIKey: VCOKEGJCZJHISM-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin) assessed as reduction in L-kynurenine formation using L-tryptophan as substrate incubated for 30 mins by microplate spectrophotometry analysis
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 310.7, ALogP 2.09, HBA 6, HBD 0, PSA 77.74, QED 0.5
Compound (SMILES): O=C(O)c1ccccc1Nc1cccc(Cl)c1-c1ccc2ccccc2c1
InChIKey: IHQHCVHDQLNOFY-UHFFFAOYSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: Displacement of 1,8-ANS from recombinant human 6His-tagged FABP3 expressed in Escherichia coli BL21 DE3 incubated for 15 mins followed by 1,8-ANS addition and measured after 3 mins by fluorescence based assay
Measurement: Ki = 1420 nM (pChEMBL 5.849999904632568)
Descriptors: MW 373.84, ALogP 6.6, HBA 2, HBD 2, PSA 49.33, QED 0.42
Compound (SMILES): CCCCc1cc(NC(=O)CCc2ccc3c(Cl)c(O)ccc3c2)c(C(=O)O)[nH]1
InChIKey: IUQPCBOOXYHWRN-UHFFFAOYSA-N
Target: Hydroxycarboxylic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDS4
Assay: Agonist activity at GPR109A receptor (unknown origin) expressed in HEK293T cell membranes after 30 mins by [35S]GTPgammaS binding based microbeta scintillation counting analysis
Measurement: EC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 414.89, ALogP 5.14, HBA 3, HBD 4, PSA 102.42, QED 0.41
Compound (SMILES): CCC[C@H]1C(=O)C(C(N)=O)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: IHTJJXVFLQWISD-HOOXPUODSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 510.61, ALogP 5.45, HBA 5, HBD 1, PSA 98.83, QED 0.44
Compound (SMILES): CCCCc1nc2c(N)nc3cc(C#N)ccc3c2n1CC(C)C
InChIKey: FOLKUNKWCIRWGQ-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 expressed in HEK-Blue cells assessed as induction of NFkappaB activation by measuring increase in SEAP level by SEAP reporter gene-based UV-vis absorbance method
Measurement: EC50 = 990 nM (pChEMBL 6)
Descriptors: MW 321.43, ALogP 4.04, HBA 5, HBD 1, PSA 80.52, QED 0.77
Compound (SMILES): Nc1ccc(F)cc1NC(=O)C1CCN(C(=O)c2cc(Cc3n[nH]c(=O)c4ccccc34)ccc2F)CC1
InChIKey: XSNNYLLCIBEWBI-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 517.54, ALogP 3.87, HBA 5, HBD 3, PSA 121.18, QED 0.35
Compound (SMILES): COC(=O)c1ccc(-n2cc(CCCOS(=O)(=O)c3ccc(C)cc3)nn2)cc1
InChIKey: VYUDJPGSULLWAS-UHFFFAOYSA-N
Target: 26S proteasome non-ATPase regulatory subunit 10 (SINGLE PROTEIN), Homo sapiens
UniProt: O75832
Assay: Binding affinity to gankyrin (unknown origin) expressed in Escherichia coli BL21 (DE3) expression system assessed as dissociation constant at 1:1 protein to compound concentration by isothermal titration calorimetry
Measurement: Kd = 532 nM (pChEMBL 6.269999980926514)
Descriptors: MW 415.47, ALogP 2.7, HBA 8, HBD 0, PSA 100.38, QED 0.32
Compound (SMILES): O=C(O)C(=O)Nc1ccc(-c2ccccc2)cc1
InChIKey: PLOROTCZCNJQOC-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 = 62000 nM (pChEMBL 4.210000038146973)
Descriptors: MW 241.25, ALogP 2.38, HBA 2, HBD 2, PSA 66.4, QED 0.79
Compound (SMILES): CC(C)N(C(=O)c1cc(C(C)(C)C)cc(C(C)(C)C)c1)c1ccc(C(=O)NO)cc1
InChIKey: IFBZBDZPCMAIAR-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus expression system using FAM-RHKK(Ac)-NH2 substrate incubated for 5 hrs by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 410.56, ALogP 5.46, HBA 3, HBD 2, PSA 69.64, QED 0.52
Compound (SMILES): Cc1ccc2nc(-c3ccc([N+](=O)[O-])cc3)[nH]c2c1
InChIKey: PFIPEWJKRTWVRM-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 253.26, ALogP 3.45, HBA 3, HBD 1, PSA 71.82, QED 0.56
Compound (SMILES): O=C(CCc1ccccc1)C(F)(F)C(=O)NCCc1ccccc1
InChIKey: LRGFYGVMUMQXCZ-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 331.36, ALogP 3.18, HBA 2, HBD 1, PSA 46.17, QED 0.76
Compound (SMILES): CN(C)S(=O)(=O)CCCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1
InChIKey: KISCJPSVCYZKED-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate incubated for 24 hrs by UV-spectrophotometry
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 465.31, ALogP 1.91, HBA 8, HBD 3, PSA 132.95, QED 0.18
Compound (SMILES): COc1ccc(-c2cnn3c(N)c(-c4ccccc4)c(OCCCN(C)C)nc23)cc1OC
InChIKey: ATYKMHIJRBRZOA-UHFFFAOYSA-N
Target: TEL/KDR (CHIMERIC PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of TEL/KDR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 447.54, ALogP 3.99, HBA 8, HBD 1, PSA 87.14, QED 0.39
Compound (SMILES): CCOc1cc(Cl)c(C(=O)N(C)C(=O)Nc2nc3ccc(CN4CCN(C)CC4)cc3s2)cc1N1CCOCC1
InChIKey: AXBPFEFMNUBLBT-UHFFFAOYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-ghrelin from human GHS-R1a stably expressed in HEK cell membrane measured after 60 mins by gamma counter method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 587.15, ALogP 4.24, HBA 9, HBD 1, PSA 90.48, QED 0.44
Compound (SMILES): CCn1nnc2c(C)c([C@@H](CC(=O)O)c3ccc4c(c3)CN(C(=O)c3ccccc3)CC4)ccc21
InChIKey: AUCYBCJRRYAJGN-DEOSSOPVSA-N
Target: Kelch-like ECH-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14145
Assay: Binding affinity to Keap1 (unknown origin) by SPR assay
Measurement: Kd = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 468.56, ALogP 4.56, HBA 5, HBD 1, PSA 88.32, QED 0.45
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1C)C(F)(F)F
InChIKey: MEGPNUDVAPPIRN-KRWDZBQOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 643.13, ALogP 4.47, HBA 7, HBD 3, PSA 128.7, QED 0.35
Compound (SMILES): O=C(O)C(=O)O.c1ccc(CC2CCN(CC3CSC4(CCCC4)S3)CC2)cc1
InChIKey: XXVSYSSDEBBIRK-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-ditolylguanidine from human Sigma 2 receptor by radioligand displacement assay
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 347.59, ALogP 5.06, HBA 3, HBD 0, PSA 3.24, QED 0.75
Compound (SMILES): CC[C@@](O)(c1cn(C(C)c2ccc3c(-c4ccc(F)cc4)cc(C(N)=O)nc3c2)nn1)C(F)(F)F
InChIKey: SJIFJFPZDNDEGR-KBEVUASJSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Negative allosteric modulation of human mGluR2 by FLIPR assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 487.46, ALogP 4.5, HBA 6, HBD 2, PSA 106.92, QED 0.39
Compound (SMILES): Cc1cc(Cl)ccc1C(=O)N(C)c1cccnc1
InChIKey: QYLQDMFJQJNRDM-UHFFFAOYSA-N
Target: Cytochrome P450 11B2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P19099
Assay: Inhibition of human CYP11B2 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycorticosterone as substrate by HTRF assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 260.72, ALogP 3.32, HBA 2, HBD 0, PSA 33.2, QED 0.83
Compound (SMILES): CCn1c(-c2ccc(F)cc2F)cs/c1=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: IJXSYBUPEOCYHZ-HEHNFIMWSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 395.46, ALogP 3.39, HBA 5, HBD 1, PSA 77.45, QED 0.74
Compound (SMILES): N#CCCN(CCc1ccccc1)CC(=O)N(CCc1ccc(S(N)(=O)=O)cc1)Cc1ccc([N+](=O)[O-])cc1
InChIKey: CCKAJIGVRVSHPG-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 264.2 nM (pChEMBL 6.579999923706055)
Descriptors: MW 549.65, ALogP 3.27, HBA 7, HBD 1, PSA 150.64, QED 0.24
Compound (SMILES): COC(=O)CN(C)C(=O)C[C@H](CCC1CCCCC1)NC(=O)c1cc(-c2c(OC)cccc2OC)n(CC(C)C)n1
InChIKey: HSEBECGWTBSSRH-QHCPKHFHSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 1850 nM (pChEMBL 5.730000019073486)
Descriptors: MW 570.73, ALogP 4.7, HBA 8, HBD 1, PSA 111.99, QED 0.33
Compound (SMILES): Cc1ccc(C)c(NC(=O)CCN2CC[C@@]3(C)c4cc(O)ccc4C[C@@H]2[C@@H]3C)c1
InChIKey: QVKRGZALEHLJFM-XYURVEJXSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from DOR in rat brain membranes incubated for 45 mins by liquid scintillation counting
Measurement: Ki = 478 nM (pChEMBL 6.320000171661377)
Descriptors: MW 392.54, ALogP 4.56, HBA 3, HBD 2, PSA 52.57, QED 0.8
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3Cc2nc3ccccc3o2)cc(OC)c1OC
InChIKey: NXKKCSAWPYGOIN-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 465.55, ALogP 4.17, HBA 7, HBD 1, PSA 86.06, QED 0.56
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)C(=O)O)o3)nc2CC2CCC2)c2ccccc12)C(F)(F)F
InChIKey: ZHTPYXZPCVSSGB-HNNXBMFYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: ThermoFluor Assay: For the RORγt construct used in the ThermoFluor assay, numbering for the nucleotide sequences was based on the reference sequence for human RORγt, transcript variant 2, NCBI Accession: NM_001001523.1 (SEQ ID NO:1). Nucleotides 850-1635 (SEQ ID NO:2) coding for the wild type human RORγt ligand binding domain (RORγt LBD) were cloned into the pHIS1 vector, a modified pET E. coli expression vector (Accelagen, San Diego), containing an in-frame N-terminal His-tag and a TurboTEV protease cleavage site (ENLYFQG, SEQ ID NO:3) upstream of the cloned insert sequence. The amino acid sequence for the RORγt construct used in the Thermofluor assay is shown as SEQ ID NO:4. ThermoFluor experiments were carried out using instruments owned by Janssen Research and Discovery, L.L.C. through its acquisition of 3-Dimensional Pharmaceuticals, Inc. 1,8-ANS (Invitrogen) was used as a fluorescent dye. Protein and compound solutions are dispensed into black 384-well polypropylene PCR microplates (Abgene) and overlayed with silicone oil (1 μL, Fluka, type DC 200) to prevent evaporation. Bar-coded assay plates are robotically loaded onto a thermostatically controlled PCR-type thermal block and then heated at a typical ramp-rate of 1° C./min for all experiments. Fluorescence was measured by continuous illumination with UV light (Hamamatsu LC6) supplied via fiber optic and filtered through a band-pass filter (380-400 nm; >6 OD cutoff). Fluorescence emission of the entire 384-well plate was detected by measuring light intensity using a CCD camera (Sensys, Roper Scientific) filtered to detect 500±25 nm, resulting in simultaneous and independent readings of all 384 wells. Images were collected at each temperature, and the sum of the pixel intensity in a given area of the assay plate was recorded versus temperature.
Measurement: Kd = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 622.69, ALogP 6.24, HBA 8, HBD 2, PSA 135.28, QED 0.21
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2cccc(C)c2)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: IXJAYHQRMNJRAS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 500.55, ALogP 6.23, HBA 3, HBD 3, PSA 82.8, QED 0.17
Compound (SMILES): CN1CCN(c2cc(-c3ccncc3)c(-c3ccc4cccc(F)c4c3)nn2)CC1
InChIKey: CHIDSEUGTZJIKU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15759
Assay: Inhibition of human p38beta
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.47, ALogP 4.25, HBA 5, HBD 0, PSA 45.15, QED 0.52
Compound (SMILES): Cc1noc(C)c1-c1cc2ncc3c(c2cc1O[C@H]1CCNC1)n(C(C)c1ccccn1)c(=O)n3C
InChIKey: NQSDHKFYTJFWTL-DAFXYXGESA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged human BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant expressed in Escherichia coli after 1 hr by TR-FRET assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 484.56, ALogP 3.91, HBA 9, HBD 1, PSA 100, QED 0.4
Compound (SMILES): CCCCNC(=O)[C@@H]1C[C@H]1[C@]12COC[C@H]1CSC(N)=N2
InChIKey: WVAFMFLAAGBATC-OXIWPEFWSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2
Measurement: IC50 = 7330 nM (pChEMBL 5.130000114440918)
Descriptors: MW 297.42, ALogP 0.99, HBA 5, HBD 2, PSA 76.71, QED 0.74
Compound (SMILES): C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(Br)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCC[N+](C)(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(N)=O
InChIKey: YWACDKZPYSQVFM-QJSKOQLASA-O
Target: Chromobox protein homolog 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95931
Assay: Inhibition of CBX7 (unknown origin) assessed as inhibition of CBX4 disruption by competitive FP assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 968.92, ALogP 0.4, HBA 10, HBD 10, PSA 295.45, QED 0.04
Compound (SMILES): ONC[C@H]1C[C@@H](n2cc(Cc3ccc(C4CC4)cc3)c3c(Cl)cccc32)[C@H](O)[C@@H](O)[C@@H]1O
InChIKey: CRWSANGHPPOCOC-QEZVQXRLSA-N
Target: Sodium/glucose cotransporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31639
Assay: Inhibition of human SGLT2
Measurement: EC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 456.97, ALogP 3.39, HBA 6, HBD 5, PSA 97.88, QED 0.37
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCCO[C@H]2Cn2cc(-c3ccc(F)cn3)cn2)c1
InChIKey: GEFBDVVSBPPDRP-QFIPXVFZSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular Ca2+ release preincubated for 30 mins followed by orexin-A stimulation by Fluo-4AM dye based fluorescence analysis
Measurement: IC50 = 2.21 nM (pChEMBL 8.65999984741211)
Descriptors: MW 447.47, ALogP 2.86, HBA 8, HBD 0, PSA 90.96, QED 0.47
Compound (SMILES): CC(C)c1ccccc1Nc1nc(Nc2ccc(N3CCN(C)CC3)cn2)ncc1Cl
InChIKey: SZRNZUUUCFGQSQ-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 = 2650 nM (pChEMBL 5.579999923706055)
Descriptors: MW 437.98, ALogP 4.89, HBA 7, HBD 2, PSA 69.21, QED 0.57
Compound (SMILES): CS(=O)(=O)c1sc(-c2cc(Cl)nc(C#N)c2)c2c1[C@H](O)C(F)(F)CC2
InChIKey: NNGUTMALIFNSPA-ZDUSSCGKSA-N
Target: Endothelial PAS domain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99814
Assay: Inhibition of HIF2-alpha in human 786-0 cells cells harboring HRE-Luc2P reporter construct incubated for 48 hrs by ONE-Glo EX reagent based luminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 404.85, ALogP 3.35, HBA 6, HBD 1, PSA 91.05, QED 0.77
Compound (SMILES): COc1cc(C(=O)N2CC(F)C2)ccc1Nc1nc2ccc(-c3ccc(NC(=O)[C@H](C)c4ccc(F)cc4)cc3)cn2n1
InChIKey: JNKUNFBRYLQETD-LJQANCHMSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of MPS1 in human HeLa cells assessed as reduction in spindle assembly checkpoint incubated for 4 hrs by p-histone H3/Hoechst 33342 staining based microscopic analysis
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 582.61, ALogP 5.82, HBA 7, HBD 2, PSA 100.86, QED 0.24
Compound (SMILES): COc1nn(-c2ccccn2)cc1C(=O)Nc1cccc(-c2nncn2C(C)C)n1
InChIKey: BLKPAPOAEPCQQA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of V5 tagged human ASK1 expressed in HEK293T cells assessed as reduction in T848 autophosphorylation incubated for 1 hr by MSD assay
Measurement: IC50 = 299 nM (pChEMBL 6.519999980926514)
Descriptors: MW 404.43, ALogP 2.76, HBA 9, HBD 1, PSA 112.64, QED 0.53
Compound (SMILES): COc1cccc2c1NC(CO)C1CC=CC21
InChIKey: YDLQDTNNGYGKAA-UHFFFAOYSA-N
Target: Protein fosB/Transcription factor jun-D (PROTEIN COMPLEX), Homo sapiens
UniProt: P17535
Assay: Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5'-GTCGGTGACTCAAAACA-3' AP1 oligonucleotide measured after 15 mins by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 231.29, ALogP 2.14, HBA 3, HBD 2, PSA 41.49, QED 0.77
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@H](COC(=O)c3ccc[nH]3)[C@@H](O)[C@H]2O)c(=O)[nH]1
InChIKey: QCPXWEFKAZRXTO-QYVSTXNMSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human MAPK14 expressed in Escherichia coli after 1 hr by Z'-LYTE assay
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 376.33, ALogP -1.49, HBA 10, HBD 5, PSA 181.37, QED 0.34
Compound (SMILES): CC(Nc1nc2c(cnn2C2CCCC2)c(=O)[nH]1)c1ccc(Cl)cc1
InChIKey: FIUCLBJMUGCQTF-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition Assay: Inhibition activities of all the N-substituted pyrazolo [3,4-d] pyrimidine ketone compounds according to the present invention to the phosphodiesterase IX are tested.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 357.85, ALogP 4.06, HBA 5, HBD 2, PSA 75.6, QED 0.74
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: MYGVGPGFPDQQRX-RSXGOPAZSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 531.7, ALogP 5.45, HBA 6, HBD 2, PSA 100.21, QED 0.3
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCCCCc1c[nH]cn1.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: APWOSIJGLAZRMM-UHFFFAOYSA-M
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]-UR-PI294 from Galphai2/Gbeta1gamma2-coupled human recombinant H3R expressed in baculovirus infected Sf9 insect cell membranes
Measurement: Ki = 0.912 nM (pChEMBL 9.039999961853027)
Descriptors: MW 415.61, ALogP 5.52, HBA 2, HBD 1, PSA 35.8, QED 0.27
Compound (SMILES): c1ccc2c(N3CCCCC3)cc(-c3ccc4c(c3)OCO4)nc2c1
InChIKey: ZIRWEISZRGNSNN-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine chloride as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 332.4, ALogP 4.62, HBA 4, HBD 0, PSA 34.59, QED 0.69
Compound (SMILES): Cc1cc(=O)n(C)cc1-c1cc(C)c2nn(C3CCNCC3)cc2c1
InChIKey: YLCPXJJLBZHNTE-UHFFFAOYSA-N
Target: Toll-like receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00206
Assay: Antagonist activity at TLR4 in human PBMC assessed as inhibition of LPS-induced TNFalpha production preincubated for 30 mins followed by LPS addition and measured after 20 hrs by HTRF assay
Measurement: IC50 > 4200 nM (pChEMBL 5.376999855041504)
Descriptors: MW 336.44, ALogP 2.94, HBA 5, HBD 1, PSA 51.85, QED 0.78
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)c(CCO)c(C3CCCCC3)c12
InChIKey: WFHRZLNMHBOJNS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 275.35, ALogP 2.14, HBA 3, HBD 3, PSA 81.77, QED 0.8
Compound (SMILES): Cc1ccc(N2C(=O)N(C)C(=O)C23CCN(C(=O)[C@H](NC(=O)c2cc(C(F)(F)F)ccc2F)C(C)C)CC3)cc1
InChIKey: BHKGLCMPKLMIIW-JOCHJYFZSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 562.56, ALogP 4.37, HBA 4, HBD 1, PSA 90.03, QED 0.43
Compound (SMILES): O=C1CCCN1Cc1cc2nccc(-c3cc(Cl)cc4c3O[C@@H](C(=O)N3CCNCC3)C4)c2s1
InChIKey: NAFSZOAFHRPSHA-OAQYLSRUSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 47 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96K76
Assay: Inhibition of USP47 (unknown origin) by biochemical assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 497.02, ALogP 3.47, HBA 6, HBD 1, PSA 74.77, QED 0.6
Compound (SMILES): C=C[C@@H](C)c1c(NCc2ccccc2N2CCN(C)CC2)cnn(C)c1=O
InChIKey: UXKWIGGELSTRMR-MRXNPFEDSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to human partial length BRPF1 (E627 to G740 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 367.5, ALogP 2.43, HBA 6, HBD 1, PSA 53.4, QED 0.8
Compound (SMILES): O=C(CC1c2ccccc2N=C(SCCCCCN2CCCC2)N1c1ccccc1)NCc1ccc(F)cc1
InChIKey: FQBDNTCNEDEMIY-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1G (SINGLE PROTEIN), Homo sapiens
UniProt: O43497
Assay: Inhibition of human Cav3.1 expressed in tsA-201 cells by patch clamp electrophysiology
Measurement: IC50 = 13500 nM (pChEMBL 4.869999885559082)
Descriptors: MW 544.74, ALogP 7.08, HBA 5, HBD 1, PSA 47.94, QED 0.26
Compound (SMILES): C[C@H](c1ccc(Cl)cc1Cl)n1nc(C(N)=O)c2ncc(N3CC([C@H]4CCCN(CCO)C4)C3)nc21
InChIKey: NLBDONGAEIAOLZ-CABCVRRESA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Antagonist activity at CCR4 in human CCRF-CEM cells assessed as inhibition of CCL22-mediated chemotaxis preincubated for 30 mins followed by CCL22 addition and measured after 60 mins in presence of 100% human serum by CellTiter-Glo assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 518.45, ALogP 2.98, HBA 8, HBD 2, PSA 113.4, QED 0.49
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](N)Cc1ccc(O)cc1)c1ccco1
InChIKey: AFPIGIHSWVQYED-DXLYGPJMSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]-DAMGO from Wistar rat mu opioid receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 671.76, ALogP 0.71, HBA 8, HBD 10, PSA 267.47, QED 0.03
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCC2CCCCC2)CC(=O)O)nn1C1CCCCC1
InChIKey: SXWKNJYKTDWHQS-NRFANRHFSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 518 nM (pChEMBL 6.289999961853027)
Descriptors: MW 511.66, ALogP 6.01, HBA 6, HBD 2, PSA 102.68, QED 0.38
Compound (SMILES): CC(C)CCNC1=CC(=O)c2ccccc2C1=O
InChIKey: JLOBMWCZCWALTQ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using isoform-specific probe substrates incubated for 15 to 30 mins by by LC-MS/MS analysis
Measurement: IC50 = 5570 nM (pChEMBL 5.25)
Descriptors: MW 243.31, ALogP 2.59, HBA 3, HBD 1, PSA 46.17, QED 0.88
Compound (SMILES): C[C@@H]1C[C@H](C(=O)O)CC[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: JQORWGARJVSRBA-NVMDKWJCSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in CD3 and CD28-stimulated human whole blood assessed as suppression of IL17 incubated for 1 hr before CD3 and CD28 stimulation for 20 hrs by AlphaLISA method
Measurement: EC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 667.61, ALogP 6.47, HBA 4, HBD 1, PSA 91.75, QED 0.29
Compound (SMILES): Cn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ncns2)cc1F
InChIKey: NCYAOGNZTIDLCT-ABAIWWIYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 455.51, ALogP 3.46, HBA 8, HBD 1, PSA 99, QED 0.61
Compound (SMILES): N#Cc1cnc2cc(OC[C@H](O)CO)c(NC(=O)CC3CSSC3)cc2c1Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
InChIKey: UVWRRZRGHPHHLL-HSZRJFAPSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin) in presence of radiolabelled gammaATP by radioisotope filter binding assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 655.17, ALogP 6.29, HBA 10, HBD 4, PSA 136.73, QED 0.13
Compound (SMILES): N#Cc1ccnc(Oc2nn([C@H]3C[C@H](F)C3)c3ncnc(N)c23)c1
InChIKey: USPIAMGRHIPYDO-MGCOHNPYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells by patch-clamp electrophysiology assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 325.31, ALogP 2.14, HBA 8, HBD 1, PSA 115.53, QED 0.78
Compound (SMILES): Cc1cn(-c2cc(CCS(N)(=O)=O)cc(NC(=O)c3ccc(C)c(Nc4nccc(-c5ccccc5)n4)c3)c2)cn1
InChIKey: YITOZDQLAMEHRT-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of recombinant human N-terminal GST-tagged PDGFRbeta cytoplasmic domain (557 to 1106 residues) expressed in baculovirus expression system using FAM-labelled P22 peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 567.68, ALogP 4.77, HBA 8, HBD 3, PSA 144.89, QED 0.23
Compound (SMILES): COc1cc2c(cc1OC)C([C@@](C)(OC)c1ccc(OC)c(OC)c1O)=NCC2
InChIKey: QCPXRYKFJUHMHK-QFIPXVFZSA-N
Target: Cocaine esterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00748
Assay: Inhibition of human CE2 using fluorescein diacetate as substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins by luminescence assay
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 401.46, ALogP 3.33, HBA 7, HBD 1, PSA 78.74, QED 0.77
Compound (SMILES): CC(=O)N1CCC(c2ccc(-c3cc(C(=O)O)cc4cc(-c5ccc(C(F)(F)F)cc5)ccc34)cc2)CC1
InChIKey: AFRXCTUPOJKNDG-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Binding affinity to TSPO receptor (unknown origin)
Measurement: Ki = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 517.55, ALogP 7.62, HBA 2, HBD 1, PSA 57.61, QED 0.3
Compound (SMILES): O=S1(=O)c2cccc3cccc(c23)N1CCCCCCN1CCN(c2nsc3ccccc23)CC1
InChIKey: DXUOUUKATHEZTO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 506.7, ALogP 5.34, HBA 6, HBD 0, PSA 56.75, QED 0.3
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2ccc3ccccc3c2)C(=O)CN(CCC(=O)O)CCc2ccccc2)cc1
InChIKey: PYCJQGYVMKZBRZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 72.5 nM (pChEMBL 7.139999866485596)
Descriptors: MW 573.72, ALogP 4.08, HBA 5, HBD 2, PSA 121.01, QED 0.23
Compound (SMILES): CCN(CC)CCNc1cc2nc3n(c(=O)c2cc1F)CC/C3=C\c1ccc(N(CC)CC)cc1O
InChIKey: CEKQGUFKTNPVPN-HMMYKYKNSA-N
Target: RecQ-like DNA helicase BLM (SINGLE PROTEIN), Homo sapiens
UniProt: P54132
Assay: Binding affinity to His-tagged BLM (642 to 1296 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as inhibition of protein interaction with 5'-biotin-labeled forked DNA measured after 1 hr by ELISA
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 493.63, ALogP 4.79, HBA 7, HBD 2, PSA 73.63, QED 0.42
Compound (SMILES): CCCCc1nc2c(N)nc3cc(OC)ccc3c2n1CC(C)C
InChIKey: BNPZZJJCBTZDEK-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 expressed in HEK-Blue cells assessed as induction of NFkappaB activation by measuring increase in SEAP level by SEAP reporter gene-based UV-vis absorbance method
Measurement: EC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 326.44, ALogP 4.17, HBA 5, HBD 1, PSA 65.96, QED 0.74
Compound (SMILES): O=C(CCCCCCCC(=O)NCCCN1c2ccccc2CCc2ccc(Cl)cc21)NO
InChIKey: VESSIZGXFMZXOB-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal GST-tagged HDAC2 (1 to 488 residues) expressed in baculovirus infected sf21 cells using RHK-K(Ac)-AMC as substrate after 60 mins by fluorimetry assay
Measurement: IC50 = 2740 nM (pChEMBL 5.559999942779541)
Descriptors: MW 472.03, ALogP 5.32, HBA 4, HBD 3, PSA 81.67, QED 0.22
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4CCOCC4)cc3)c2C)cc(OC)c1OC
InChIKey: ARDORRMBSSVSKV-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay
Measurement: IC50 = 2356 nM (pChEMBL 5.630000114440918)
Descriptors: MW 420.51, ALogP 4.59, HBA 6, HBD 0, PSA 53.05, QED 0.58
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)C(=O)O)o3)nc2CC2CCCCC2)c(C(F)F)c1F)C(F)(F)F
InChIKey: ZHSFCHXKHOJYIG-SFHVURJKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL-17a production
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 682.71, ALogP 7.33, HBA 8, HBD 2, PSA 135.28, QED 0.19
Compound (SMILES): CC(=O)N(CCCc1cc2c(=O)[nH]c(N)nc2[nH]1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
InChIKey: DMNZBKJKYWYHAB-KRWDZBQOSA-N
Target: Trifunctional purine biosynthetic protein adenosine-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22102
Assay: Inhibition of GARFTase in human KB cells expressing RFC/FRalpha/PCFT assessed as reduction in cell growth after 96 hrs in presence of folic acid by Cell-Titer Blue assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 498.5, ALogP 0.87, HBA 7, HBD 6, PSA 211.57, QED 0.22
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc4c(c3)COB4O)ncc2C(F)(F)F)c1
InChIKey: CATGYHXLDRQPGZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 455.21
Compound (SMILES): CCn1sc(=O)n(CCc2ccccc2)c1=O
InChIKey: HYCIUMWKUONOEF-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) assessed as reduction in IsdA (64 to 323 residues) transpeptidation incubated for 20 mins by SDS-PAGE analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 250.32, ALogP 1.33, HBA 5, HBD 0, PSA 44, QED 0.82
Compound (SMILES): C[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(N4CCN(C)CC4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: NWHWDHYNFFLIQL-KVYOAWSJSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 237 nM (pChEMBL 6.619999885559082)
Descriptors: MW 445.54, ALogP 3.52, HBA 6, HBD 0, PSA 73.12, QED 0.7
Compound (SMILES): O=c1ccc(-c2cc(C(F)(F)F)c3nn([C@@H]4CCNC[C@H]4F)cc3c2)c2n1CCC2
InChIKey: WLDNDKUPNXWOSV-SJLPKXTDSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in human PBMC assessed as inhibition of DOTAP-ssRNA40 induced TNFalpha production preincubated for 30 mins followed by ssRNA40 addition measured after 20 hrs by HTRF assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 420.41, ALogP 3.7, HBA 5, HBD 1, PSA 51.85, QED 0.64
Compound (SMILES): CC(=O)N1N=C(c2cc(O)c(O)c([N+](=O)[O-])c2)CC1c1nccs1
InChIKey: IAXKUAVFDVWNOY-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB using kynuramine as substrate by fluorescence based assay
Measurement: IC50 = 68200 nM (pChEMBL 4.170000076293945)
Descriptors: MW 348.34, ALogP 2.16, HBA 8, HBD 2, PSA 129.16, QED 0.5
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccc(F)cc2)cc(OC)c1OC
InChIKey: ZZVJXULAXIUEGR-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 30700 nM (pChEMBL 4.510000228881836)
Descriptors: MW 485.56, ALogP 3.61, HBA 6, HBD 2, PSA 89.13, QED 0.59
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCN2CCN(c3ccc(C)c(C)c3)CC2)c(=O)c2c(F)cccc12
InChIKey: OHJSNUFEOMRVNA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from 5-HT2C receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 462 nM (pChEMBL 6.329999923706055)
Descriptors: MW 523.61, ALogP 2.54, HBA 8, HBD 1, PSA 96.77, QED 0.43
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)C(=O)O)o3)nc2CN2CCCC(F)(F)C2)c(C(F)F)c1F)C(F)(F)F
InChIKey: SBHFAQDIXHCJBY-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to recombinant human RORgammat transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 705.65, ALogP 6.05, HBA 9, HBD 2, PSA 138.52, QED 0.23
Compound (SMILES): N=c1oc2c(O)cccc2cc1C(=O)Nc1ccccc1F
InChIKey: ZMNXHPLQWYRJBV-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of recombinant AKR1C3 (unknown origin) assessed as reduction in S-tetralol-induced dehydrogenase activity by measuring NADPH level
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 298.27, ALogP 3.01, HBA 4, HBD 3, PSA 86.32, QED 0.68
Compound (SMILES): Nc1nc(-c2ccc(OCC(O)CO)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: JGSJJZGTGOMAIC-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-NECA from human A2A receptor expressed in CHO cells
Measurement: Ki = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 393.4, ALogP 0.86, HBA 9, HBD 3, PSA 127.9, QED 0.44
Compound (SMILES): CCC[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C(F)(F)F)c4)nc(-c4ccccc4F)c3CC[C@H]12
InChIKey: LJOUWKBZWQZQFF-PNLFWNEXSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 520.53, ALogP 6.63, HBA 5, HBD 0, PSA 79.53, QED 0.36
Compound (SMILES): COc1cc(C2=CC3=NOC[C@H](c4cc(F)c(F)c(F)c4)N3CCC2)ccc1-n1cnc(C)c1
InChIKey: QMLSYCXFYJARPA-JOCHJYFZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of MK499 binding to human ERG
Measurement: IC50 = 2608 nM (pChEMBL 5.579999923706055)
Descriptors: MW 468.48, ALogP 5.17, HBA 6, HBD 0, PSA 51.88, QED 0.5
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](CN)NC(=O)[C@@H](N)Cc1ccc(O)cc1)c1ccco1
InChIKey: GWPNDXQIMPCGRT-LYGMZBLVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at mu opioid receptor (unknown origin) expressed in human HEK293 cells assessed as increase in cAMP accumulation using [3H]-cAMP as substrate measured after 30mins by liquid scintillation counting method
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 562.63, ALogP -0.07, HBA 8, HBD 7, PSA 215.8, QED 0.13
Compound (SMILES): CC(C)c1onc(-c2c(Cl)cccc2Cl)c1COc1ccc(-c2nc3ccc(C(=O)O)cc3n2CC2CCCCC2)c(F)c1
InChIKey: XVTXWCTWXZUIEK-UHFFFAOYSA-N
Target: Vitamin D3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P11473
Assay: Antagonist activity at human VDR transfected in HEK293T cells measured after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 839.5 nM (pChEMBL 6.079999923706055)
Descriptors: MW 636.55, ALogP 9.79, HBA 6, HBD 1, PSA 90.38, QED 0.17
Compound (SMILES): N=C(N)Nc1ccc(CNC(=O)[C@@H](NC(=O)c2ccccc2-c2ccccc2)c2ccc(OCc3ccccc3)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: PPHBDIRUFHOAAV-WAQYZQTGSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Gly-Leu-Lys-Arg-Gly-Gly-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition measured for 15 mins by fluorimetric analysis
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 583.69, ALogP 6.03, HBA 4, HBD 5, PSA 129.33, QED 0.1
Compound (SMILES): CCOC(=O)c1ccc(N2CCN(c3nc(N)c4nc(-c5ccco5)sc4n3)CC2)cc1
InChIKey: KRHWODOVQMCRFB-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241383 from human A2AR expressed in CHO cells by competitive binding assay
Measurement: Ki = 279 nM (pChEMBL 6.550000190734863)
Descriptors: MW 450.52, ALogP 3.43, HBA 10, HBD 1, PSA 110.61, QED 0.46
Compound (SMILES): Cc1cccc(C)c1OCC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21
InChIKey: GRHZLQBPAJAHDM-SPRQWYLLSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing protease cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 0.069 nM (pChEMBL 10.15999984741211)
Descriptors: MW 602.73, ALogP 4.26, HBA 7, HBD 3, PSA 115.35, QED 0.27
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)cc1F
InChIKey: GHOSFOBBUGQTRM-WBMJQRKESA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): COc1cc(/C=C/C(=O)O)ccc1OCc1cn(-c2ccc(C)cc2)nn1
InChIKey: SWXWXTJVPKKJQB-UXBLZVDNSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 using p-nitrophenyl acetate as substrate by UV-VIS spectrophotometric analysis
Measurement: IC50 = 4220 nM (pChEMBL 5.380000114440918)
Descriptors: MW 365.39, ALogP 3.26, HBA 6, HBD 1, PSA 86.47, QED 0.65
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cn(Cc2cccc3occc23)c1=O
InChIKey: BGQOHRSOMBQTCU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 365.39, ALogP 1.89, HBA 5, HBD 2, PSA 93.34, QED 0.72