lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1ccc(Oc2cc(Cl)c(Cl)cc2Cl)cn1
InChIKey: FHQDBJHRQZGYOZ-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of human MPO peroxidase activity in presence of H2O2 measured at 30 secs time interval for 5 mins by amplex red reagent based fluorescence assay
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 289.55, ALogP 4.42, HBA 3, HBD 1, PSA 48.14, QED 0.83
Compound (SMILES): Cn1cc(-c2ccncc2)cc(N)c1=O
InChIKey: KXFHELHAHLKBTH-UHFFFAOYSA-N
Target: Aurora kinase B/Inner centromere protein (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQS7
Assay: Inhibition of human full length N-terminal GST-tagged Aurora B (1 to 344 end residues)/His-tagged INCENP (803 to 918 end residues) expressed in baculovirus expression system using fluorescence-labeled FL-Peptide 21 as substrate after 60 mins in presence of ATP by fluorescence assay based Cheng-Prusoff equation analysis
Measurement: Ki = 102700 nM (pChEMBL 3.990000009536743)
Descriptors: MW 201.23, ALogP 1.03, HBA 4, HBD 1, PSA 60.91, QED 0.75
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(S(C)(=O)=O)cc3)CC2)nc2ccn(COCc3ccccc3)c12
InChIKey: YKLUIHDRLLWUGN-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase infected in human MT4 cells assessed as reduction in biotin-dUTP incorporation
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 650.81, ALogP 6.37, HBA 10, HBD 1, PSA 122.37, QED 0.17
Compound (SMILES): CCn1c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc2n(CC)c1=O
InChIKey: HSODJMGBIACYNG-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of PARG in human HeLa cells assessed as induction of MMS-induced PAR chains preincubated for 1 hr followed by MMS addition and measured after 1 hr by Alexofluor 488-conjugated secondary antibody and Hoechst 33342 staining based assay
Measurement: EC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 351.43, ALogP 1.03, HBA 6, HBD 1, PSA 90.17, QED 0.87
Compound (SMILES): C[C@H](NC(=O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCC1C2CC3CC(C2)CC1C3
InChIKey: QKYJTOQRNVBDKV-RYJASOEVSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S immunoproteasome beta-1 using Ac-PAL-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 807.99, ALogP 5.11, HBA 8, HBD 6, PSA 184.19, QED 0.12
Compound (SMILES): CC(F)(F)c1cc(Nc2nc(NC3CC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: NBLZOFNGJDPRRM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 487.38, ALogP 5.41, HBA 7, HBD 2, PSA 88.51, QED 0.45
Compound (SMILES): CC(=O)Nc1ccc(-c2ccnc(Nc3cccc(NC(=O)CCCCCCC(=O)NO)c3)n2)cc1.Cl
InChIKey: VCXVTTLIECDRQK-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Arg-His-Lys-Lys(Ac) as substrate preincubated with enzyme followed by substrate addition for 2 hrs and measured for 1.5 hrs at 15 mins time interval by fluorescence assay
Measurement: IC50 = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 490.56, ALogP 4.63, HBA 7, HBD 5, PSA 145.34, QED 0.14
Compound (SMILES): O=C(O)CCCC(=O)Nc1cc(Nc2cccc(Cl)c2)ncn1
InChIKey: DIQMCPYEEIZMCH-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P21860
Assay: Inhibition of recombinant human GST-tagged EGFR L858R mutant cytoplasmic domain expressed in baculovirus expression system using FAM-labeled peptide as substrate after 10 mins by mobility shift assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 334.76, ALogP 3.07, HBA 5, HBD 3, PSA 104.21, QED 0.72
Compound (SMILES): CC(=O)Nc1ccc(-c2ccnc(Nc3ccc(NC(=O)CCCCC(=O)NO)cc3)n2)cc1.O=C(O)C(F)(F)F
InChIKey: DICWOTWIWZRBEQ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Arg-His-Lys-Lys(Ac) as substrate preincubated with enzyme followed by substrate addition for 2 hrs and measured for 1.5 hrs at 15 mins time interval by fluorescence assay
Measurement: IC50 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 462.51, ALogP 3.85, HBA 7, HBD 5, PSA 145.34, QED 0.17
Compound (SMILES): CSc1ncc2c(n1)Nc1n[nH]c(C)c1N=C2c1cccc(F)c1
InChIKey: FKJKIYNCODEVEC-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using STK S2 as substrate after 40 mins by HTRF assay
Measurement: IC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 340.39, ALogP 3.6, HBA 6, HBD 2, PSA 78.85, QED 0.43
Compound (SMILES): Cc1nc(C)c(Cn2c(=O)n(Cc3cnn(C)c3)c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc32)s1
InChIKey: QWKOOWUDRSFHOL-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of PARG in human HeLa cells assessed as induction of MMS-induced PAR chains preincubated for 1 hr followed by MMS addition and measured after 1 hr by Alexofluor 488-conjugated secondary antibody and Hoechst 33342 staining based assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 514.63, ALogP 1.9, HBA 10, HBD 1, PSA 120.88, QED 0.4
Compound (SMILES): O=c1cc(Cc2ccc(-c3cccc(F)c3)cc2)[nH]c(=O)n1O
InChIKey: XJWRAAIBPDHBKO-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant HIV1 reverse transcriptase RNase H expressed in Escherichia coli JM109 using RNA/DNA duplex substrate HTS1 as substrate
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 312.3, ALogP 2.17, HBA 4, HBD 2, PSA 75.09, QED 0.73
Compound (SMILES): NS(=O)(=O)c1cc(NC(=O)c2ccc(F)cc2)c(OC(=O)c2ccc(F)cc2)c([N+](=O)[O-])c1
InChIKey: MTYPLAVRZHMQJM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of carbonic anhydrase 9 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 477.4, ALogP 2.99, HBA 7, HBD 2, PSA 158.7, QED 0.24
Compound (SMILES): N#CCC(=O)N/N=C1\C(=O)Nc2ccc(S(=O)(=O)N3CCOCC3)cc21
InChIKey: WPPDHWSWHZDVQN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged recombinant human EGFR T790M mutant expressed in baculovirus infected Sf21 insect cells preincubated for 5 mins followed by ATP addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 137.3 nM (pChEMBL 6.860000133514404)
Descriptors: MW 377.38, ALogP -0.61, HBA 7, HBD 2, PSA 140.96, QED 0.67
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(-c3ccc4nc(C)oc4c3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: LPXQSBYJBKPORF-SNRMKQJTSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Inhibition of TYRO3 (unknown origin) using 5'-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 433.56, ALogP 5.62, HBA 7, HBD 2, PSA 89, QED 0.41
Compound (SMILES): Fc1cc(F)cc(Nc2nc(NC3CC(F)(F)C3)nc(-c3nc(C(F)(F)F)cs3)n2)c1
InChIKey: WGWIGBTYVJCEKX-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 464.37, ALogP 5.25, HBA 7, HBD 2, PSA 75.62, QED 0.5
Compound (SMILES): COc1ccc2c(=O)cc(C(=O)NCCC3CCN(Cc4ccccc4)CC3)[nH]c2c1
InChIKey: SULOYNMFUTYGFY-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human 5-lipoxygenase using arachidonic acid as substrate pretreated for 10 mins followed by substrate and ATP addition and measured after 20 mins by H2DCFDA probe based fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 419.53, ALogP 3.57, HBA 4, HBD 2, PSA 74.43, QED 0.61
Compound (SMILES): O=c1cc(-c2ccc(OCCOCCn3cc(CN(CCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)Cc4ccccc4)nn3)cc2)oc2ccccc12
InChIKey: QBGPQSPVZIFFBR-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP in human MCF7/MX100 cells assessed as reversal of topotecan resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 760.85, ALogP 8, HBA 11, HBD 0, PSA 122.06, QED 0.08
Compound (SMILES): CCc1cccc(Nc2c(N)oc3cnccc23)c1
InChIKey: LYFPKCQSGQGJQY-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 253.31, ALogP 3.72, HBA 4, HBD 2, PSA 64.08, QED 0.75
Compound (SMILES): CN(C)CCOc1cc(-c2ncc(-c3ccc(-c4cnco4)cn3)o2)nc(-c2ncc(-c3ccc(-c4cnco4)cn3)o2)c1
InChIKey: RTDXQIFIVDWYRY-UHFFFAOYSA-N
Target: Myotonin-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q09013
Assay: Inhibition of DMPK (unknown origin) by ATP competition assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 588.58, ALogP 5.77, HBA 13, HBD 0, PSA 155.26, QED 0.19
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(Oc3ccccc3)cc2)[C@H]1NC(C)=O
InChIKey: BWDGROPAFQXXFI-JIMJEQGWSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: A5Z252
Assay: Inhibition of Influenza A virus A/Anhui/1/2005(H5N1) neuraminidase N1 H274Y mutant using fluorogenic MUNANA as substrate preincubated for 10 mins followed by substrate addition measured after 40 to 60 mins by fluorescence-based assay
Measurement: IC50 = 363.87 nM (pChEMBL 6.440000057220459)
Descriptors: MW 466.58, ALogP 4.43, HBA 5, HBD 3, PSA 96.89, QED 0.45
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3cccc(Cl)c3)CC2)cc(C(C)(C)C)c1O
InChIKey: RYQSPKQMKQUAEH-ZHACJKMWSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A using p-tyramine as substrate incubated for 15 mins followed by substrate addition measured for 20 mins by fluorescence assay
Measurement: IC50 = 65100 nM (pChEMBL 4.190000057220459)
Descriptors: MW 511.15, ALogP 7.07, HBA 3, HBD 2, PSA 52.57, QED 0.39
Compound (SMILES): CN1CCOC(Cn2cnc(-c3cc(C(=O)O)ccn3)c2)C1
InChIKey: XVIKJBZPEYLLFN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-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 302.33, ALogP 0.97, HBA 6, HBD 1, PSA 80.48, QED 0.91
Compound (SMILES): Cc1cc(Nc2c(N)oc3cnccc23)ccc1Cl
InChIKey: XMVLUDJEPRQDRU-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 273.72, ALogP 4.12, HBA 4, HBD 2, PSA 64.08, QED 0.74
Compound (SMILES): c1ccc2c(CCn3cnc(-c4cc(-c5c[nH]nn5)ccn4)c3)cccc2c1
InChIKey: MSVYMBSJDYYFOX-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PHF8 expressed in baculovirus infected Sf9 cells using H3K9mel-biotin labelled peptide as substrate measured after 15 mins by Lance TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 366.43, ALogP 4.13, HBA 5, HBD 1, PSA 72.28, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(NC(=O)Nc2ccc(F)cc2)c(O)c([N+](=O)[O-])c1
InChIKey: JYHLTIJXWVWYDU-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of carbonic anhydrase 9 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 370.32, ALogP 1.73, HBA 6, HBD 4, PSA 164.66, QED 0.36
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(C(F)(F)F)c(Cl)c2)cc1NC(=O)C1(c2cc(NCCCN3CCN(C)CC3)ncn2)CC1
InChIKey: GZCIDSUBIQFYQY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF (unknown origin)
Measurement: IC50 = 29.7 nM (pChEMBL 7.53000020980835)
Descriptors: MW 630.11, ALogP 5.43, HBA 7, HBD 3, PSA 102.49, QED 0.26
Compound (SMILES): COc1ccc(C(=O)c2cn(CC3CCOCC3)c3c(O)cccc23)cc1
InChIKey: SXDMYMPKIVFCAN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at N-terminal HA-tagged human CB2 receptor expressed in HEK293 cells transfected with YFP-Epac-RLuc assessed as increase in forskolin-stimulated cAMP level by BRET assay
Measurement: IC50 = 271.7 nM (pChEMBL 6.570000171661377)
Descriptors: MW 365.43, ALogP 4.01, HBA 5, HBD 1, PSA 60.69, QED 0.69
Compound (SMILES): COc1cc(Br)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: BLKDIABUNZWHMB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-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 404.22, ALogP 3.32, HBA 6, HBD 1, PSA 86.47, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N(CCC(N)=O)CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: XPCLAEZZZWGJKG-IIQVFVSRSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 4050.51
Compound (SMILES): CCCC(C)Nc1ncc2c(-c3ccc(CN4CCN(C)CC4)cc3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: PGXKVCTXUZHTHO-ADSZBJKRSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) using 5'-FAM-KKKKEEIYFFF-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 490.7, ALogP 4.92, HBA 7, HBD 2, PSA 69.45, QED 0.47
Compound (SMILES): Cc1cc(C)cc(Nc2cc(NC3CCC3)c3ncc(C(N)=O)n3n2)c1
InChIKey: KHHOUSOYYOKZNO-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IFNalpha-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 350.43, ALogP 3.15, HBA 6, HBD 3, PSA 97.34, QED 0.66
Compound (SMILES): COc1ccc(F)c(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: PUYRUGBORWDDDV-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 472.46, ALogP 5.06, HBA 7, HBD 2, PSA 84.85, QED 0.57
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CN(c4cccnc4)C3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: MOFOELJBPOCBKQ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 492.46, ALogP 4.25, HBA 8, HBD 2, PSA 91.75, QED 0.49
Compound (SMILES): Fc1c(Cl)cccc1Cn1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: INWJOKORMBHXJB-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: PHF8 Assay: The ability of test compounds to inhibit the activity of PHF8 was determined in 384-well plate format under the following reaction conditions: 3 nM PHF8, 200 nM H3K9me1-biotin labeled peptide (Anaspec cat #64358), 0.5 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified-histone H3 lysine 9/lysine27 (H3K9/K27) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 0.5 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 600 nM H3K9me1-biotin labeled peptide and 1.5 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 9 nM PHF8 to initiate the reaction. The reaction mixture was incubated at rt for 15 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 1 nM Europium-anti-unmodified H3K9/K27 antibody. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 354.78, ALogP 3.57, HBA 5, HBD 1, PSA 72.28, QED 0.61
Compound (SMILES): O=C(O)c1ccnc(-c2ncn(CC3CC3)c2-c2ccc(F)cc2)c1
InChIKey: CRVQLJOEUPYQFD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 337.35, ALogP 3.86, HBA 4, HBD 1, PSA 68.01, QED 0.77
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2CC(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChIKey: PWXAIRIXMQTTSE-DCFHFQCYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant in human Neurospheres assessed as reduction in 2-hydroxyglutarate production by LC-MS/MS analysis
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 597, ALogP 4.71, HBA 6, HBD 1, PSA 119.29, QED 0.4
Compound (SMILES): O=C(O)c1ccnc(-c2cn(Cc3ccc(F)cc3)cn2)c1
InChIKey: TYQVGBHPIVDCJP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-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 297.29, ALogP 2.83, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): Cc1ccc(CN2C(=O)C(=NNC(=O)c3ccc(S(N)(=O)=O)cc3)c3ccccc32)cc1
InChIKey: ZJDMHDUDIVULMB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 81.2 nM (pChEMBL 7.090000152587891)
Descriptors: MW 448.5, ALogP 2.32, HBA 5, HBD 2, PSA 121.93, QED 0.58
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccc(Cl)cc3Cl)n2-c2ccccc2)cc1
InChIKey: RWOGWGFZPPSAHY-DAFNUICNSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by Lineweaver-Burk plot analysis
Measurement: Ki = 2780 nM (pChEMBL 5.559999942779541)
Descriptors: MW 476.41, ALogP 5.39, HBA 5, HBD 1, PSA 77.45, QED 0.43
Compound (SMILES): FC(F)(F)c1[nH]nnc1-c1ccnc(-c2cn(CC3CCOc4ccccc43)cn2)c1
InChIKey: XZDINZFIWOOKIK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 426.4, ALogP 4.32, HBA 6, HBD 1, PSA 81.51, QED 0.53
Compound (SMILES): COc1ccc(-c2cs/c(=N\c3ccc(S(N)(=O)=O)cc3)n2-c2ccccc2)cc1
InChIKey: CCMWVFHINAQHDU-GYHWCHFESA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by Lineweaver-Burk plot analysis
Measurement: Ki = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 437.55, ALogP 4.09, HBA 6, HBD 1, PSA 86.68, QED 0.51
Compound (SMILES): CC(C)CNc1nc(NC(C)(C)C#N)nc(-c2cc(O)ccc2F)n1
InChIKey: SXDPYZOSOGORMF-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132C mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 90 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 344.39, ALogP 3.17, HBA 7, HBD 3, PSA 106.75, QED 0.74
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C(F)(F)F)nc(-c2ccnc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: OKFOLQBIBWUZIG-PHDIDXHHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 449.28, ALogP 4.07, HBA 7, HBD 2, PSA 88.51, QED 0.67
Compound (SMILES): CC(=O)N1CCN(c2ccc(/C=C/c3cc(Cl)cc(C(O)(c4cccnc4)C(C)C)c3)cc2)CC1
InChIKey: RLRRAQZTOSMYSH-VOTSOKGWSA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of recombinant CYP21 (unknown origin) expressed in human AD293 cells using 17alpha-hydroxyprogesterone as substrate pretreated for 60 mins followed by substrate addition and measured after 45 mins by LC/MS analysis
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 490.05, ALogP 5.47, HBA 4, HBD 1, PSA 56.67, QED 0.47
Compound (SMILES): O=S(=O)(Nc1nnc2cc(OCC34CC5CC(CC(C5)C3)C4)c(C3CC3)cn12)C(F)F
InChIKey: BZAYZAJIZQCRHW-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Electrophysiological Assay (EP) (In Vitro Assay): The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating. NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured using the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaC12, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaC12, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolarity in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO. Controls and representative compounds of the invention were applied to the recording chamber through a 4-pinch or 8-pinch valve bath perfusion system manufactured by ALA Scientific Instruments.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 452.53, ALogP 4.17, HBA 6, HBD 1, PSA 85.59, QED 0.68
Compound (SMILES): OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCN(CCCCCc2ccc(F)cc2)CC1
InChIKey: UBNDBTRGSCEYOS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]Ketanserin from 5-HT2A receptor (unknown origin) by radioligand binding assay
Measurement: Ki = 889 nM (pChEMBL 6.050000190734863)
Descriptors: MW 443.91, ALogP 6.19, HBA 2, HBD 1, PSA 23.47, QED 0.41
Compound (SMILES): CCOC(=O)c1c(-c2cc(Br)ccc2F)[nH]c2c1cc(O)c1ccccc12
InChIKey: KBISZUDAMOJRBC-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of mPGES-1 in microsomal membranes isolated from IL-1beta-stimulated human A549 cells preincubated for 15 mins followed by PGH2 addition measured after 1 mins by RP-HPLC analysis
Measurement: IC50 = 2130 nM (pChEMBL 5.670000076293945)
Descriptors: MW 428.26, ALogP 5.77, HBA 3, HBD 2, PSA 62.32, QED 0.41
Compound (SMILES): COc1cc2c(=O)n([C@@H](C(=O)N3CC(C#N)C3)C(C)C)c3c4cc[nH]c4ncc3c2cc1OC
InChIKey: KOGMMWPHFNPQDE-OAQYLSRUSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter-binding method
Measurement: IC50 = 1171 nM (pChEMBL 5.929999828338623)
Descriptors: MW 459.51, ALogP 3.23, HBA 7, HBD 1, PSA 113.24, QED 0.46
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCC2CCC(F)(F)CC2)c1
InChIKey: MBWGIVXATSPGAT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-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 337.33, ALogP 3.17, HBA 5, HBD 1, PSA 77.24, QED 0.91
Compound (SMILES): CN(C)CCCn1cnc(-c2cc(C(=O)O)ccn2)c1
InChIKey: GRMUJVXRUPGPQV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-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 274.32, ALogP 1.59, HBA 5, HBD 1, PSA 71.25, QED 0.87
Compound (SMILES): FC1(F)CCC(Nc2nc(Nc3cncc(C(F)(F)F)c3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: LRFCOIWENOAQEZ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 505.37, ALogP 5.71, HBA 7, HBD 2, PSA 88.51, QED 0.43
Compound (SMILES): COc1c(-c2ccccc2)oc2c(ccc3ccoc32)c1=O
InChIKey: JANBLZHPNGBWAO-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 expressed in HEK293 cells using 3-cyano-7-ethoxycoumarin substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay relative to control
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 292.29, ALogP 4.21, HBA 4, HBD 0, PSA 52.58, QED 0.55
Compound (SMILES): Fc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-c3nc(F)ccc3F)n2)c1
InChIKey: NODRFDKTDCPLDT-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 440.35, ALogP 4.83, HBA 6, HBD 2, PSA 75.62, QED 0.44
Compound (SMILES): Cc1[nH]nc(N)c1-c1cccc(OC(F)(F)F)c1
InChIKey: TZWCJEQQTGCAPE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged NIK (M1 to P947 residues) expressed in Sf9 insect cells using AKDVDQGSLCTSFVGTLQY peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 257.21, ALogP 2.87, HBA 3, HBD 2, PSA 63.93, QED 0.87
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1OC(=O)[C@H]1C(C)C)C(C)C)C(=O)O
InChIKey: PDPYJYDVMZXUKQ-ZDEQEGDKSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human Jurkat cell lysate using Suc-LLVY-AMC as substrate pretreated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 356.42, ALogP 0.55, HBA 5, HBD 3, PSA 121.8, QED 0.55
Compound (SMILES): CCn1c(=O)n(Cc2cc(C)no2)c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc21
InChIKey: MWUNZTNMRPOPOH-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 329 nM (pChEMBL 6.480000019073486)
Descriptors: MW 418.48, ALogP 1.36, HBA 8, HBD 1, PSA 116.2, QED 0.65
Compound (SMILES): Cc1ccc(-c2ccc(Sc3cc(=O)n(O)c(=O)[nH]3)cc2)cc1
InChIKey: FYZHSQSMLKYSON-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 326.38, ALogP 2.9, HBA 5, HBD 2, PSA 75.09, QED 0.57
Compound (SMILES): Nc1nc2oc3ccc(C4CCS(=O)(=O)CC4)cc3c(=O)c2cc1C(=O)O
InChIKey: YLXHHSZCWBYDQH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Kinase Assays: Kinase assays are commonly used for determining the ability of a small molecule to inhibit enzyme activity. By measuring the degree of phosphorylation of a substrate at varying concentrations of inhibitor, the concentration of inhibitor resulting in 50% enzymatic activity (IC50) can be obtained. The IC50 is defined as the inflection point of the sigmoidal graph obtained when plotting substrate phosphorylation vs. inhibitor concentration. Experiments were conducted during development of embodiments herein using radiolabeled ATP to detect substrate phosphorylation in the presence of amlexanox analogs to determine the potency (IC50) of said analogs.TBK1 (residues 1-657) and IKKε (residues 1-655) were purified from insect cells to ≥90% purity by coomassie staining. Reactions containing 50 nM TBK1 or IKKε, 7 μM myelin basic protein (MBP), and inhibitor in reaction buffer (50 mM HEPES pH 7.5, 10 mM NaCl, 10 mM MgCl2, 1 mM DTT) were initiated with 5 μM ATP spiked with [γ-32P]-ATP and allowed to proceed for 30 minutes at room temperature. Reactions were quenched with SDS gel loading dye, run on 4-15% SDS-PAGE gels, and imaged on phosphorimaging screens. Band intensities corresponding to phosphorylated MBP were quantified with ImageQuant and the data analyzed in Prism 6. Dose-response assay band intensities were normalized and fit to a sigmoidal dose-response equation with the Hill slope fixed at −1 and the top constrained to 100.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 388.4, ALogP 1.91, HBA 7, HBD 2, PSA 140.56, QED 0.63
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)N3CCc4ccccc43)cc2)cc1
InChIKey: GXNJWSJMKRTTPH-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Displacement of [3H]-Digoxin from recombinant human GST-fused RORgammat LBD after 1 to 4 hrs by scintillation counting method
Measurement: IC50 < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 490.63, ALogP 4.53, HBA 4, HBD 1, PSA 83.55, QED 0.53
Compound (SMILES): Cc1ccc(NC(=S)N/N=C/c2ccc(-c3cc(C(F)(F)F)ccc3Cl)o2)cc1
InChIKey: OUIDNXRNIUBSAA-OPEKNORGSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of recombinant human Ptp1B using p-nitrophenyl phosphate as substrate preincubated for 10 mins followed by substrate addition and measured every minute for 10 mins by UV-VIS spectrophotometric analysis
Measurement: IC50 = 38200 nM (pChEMBL 4.420000076293945)
Descriptors: MW 437.87, ALogP 6.25, HBA 3, HBD 2, PSA 49.56, QED 0.29
Compound (SMILES): CCCCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1C=C[C@@](C)(O)C[C@@H]21
InChIKey: PGZISGZFEFJPOZ-WHSLLNHNSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from recombinant human full length CB2 receptor expressed in HEK293 cell membranes after 90 mins by topcount method
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 330.47, ALogP 4.71, HBA 3, HBD 2, PSA 49.69, QED 0.62
Compound (SMILES): Nc1oc2c(-c3ccc(F)cc3)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: BIIAFYSYDDAKLC-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 371.77, ALogP 5.75, HBA 4, HBD 2, PSA 64.08, QED 0.48
Compound (SMILES): C=C1C(=O)N[C@@H](C)C(=O)N(C)[C@@H](C)C(=O)N[C@@H]([C@H](OC(=O)[C@@H](NC(C)=O)[C@H](O)C(C)C)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)OC)C(=O)OC[C@H](NC(C)=O)C(=O)O[C@H](Cc2ccccc2)C(=O)N1C
InChIKey: WRGMBKWSZGVFLV-MJZZTYLPSA-N
Target: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas (SINGLE PROTEIN), Homo sapiens
UniProt: Q5JWF2
Assay: Inhibition of Gs coupled adrenergic beta2 receptor in HEK293 cells assessed as reduction in isoproterenol-induced cAMP production pretreated for 1 hr followed by isoproterenol addition and measured after 30 mins by FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 946.07, ALogP -1.04, HBA 15, HBD 5, PSA 285.69, QED 0.1
Compound (SMILES): COc1ccccc1NC(=O)Nc1cc(S(N)(=O)=O)ccc1O
InChIKey: TYTZFKRSGVNIDM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 23.2 nM (pChEMBL 7.630000114440918)
Descriptors: MW 337.36, ALogP 1.69, HBA 5, HBD 4, PSA 130.75, QED 0.63
Compound (SMILES): COc1cc2c(=O)n(CCCN(C)C)c3c4cc[nH]c4ncc3c2cc1OC
InChIKey: NWCQHSKXXCBBMX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter-binding method
Measurement: IC50 = 95.62 nM (pChEMBL 7.019999980926514)
Descriptors: MW 380.45, ALogP 3, HBA 6, HBD 1, PSA 72.38, QED 0.52
Compound (SMILES): CNC(=S)NCC1(C)CCc2ccc3ccc(OC)cc3c21
InChIKey: KVGRMJYOMLPHCE-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 314.45, ALogP 3.15, HBA 2, HBD 2, PSA 33.29, QED 0.85
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C/c2ccc(N3CCN(C(=O)c4ccco4)CC3)cc2)cc1
InChIKey: BJPLOQHFOHIRRH-LFVJCYFKSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye-based stopped-flow assay
Measurement: Ki = 1788.6 nM (pChEMBL 5.75)
Descriptors: MW 453.52, ALogP 2.34, HBA 7, HBD 2, PSA 121.24, QED 0.44
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)NN=C2C(=O)Nc3ccc(Br)cc32)cc1
InChIKey: IOGVSTUWIYEBFB-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 40.2 nM (pChEMBL 7.400000095367432)
Descriptors: MW 423.25, ALogP 1.18, HBA 5, HBD 3, PSA 130.72, QED 0.64
Compound (SMILES): CN1CCN(C2(CNC3CCN(c4cccc(-c5cc6cc(F)ccc6[nH]5)c4)CC3)CCC2)CC1
InChIKey: IKTPSOBWZZCXTI-UHFFFAOYSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Biological Assay: To optimize p97 inhibitors, the C-5 trifluoromethylated trifluoromethylated indole 12 was generated as a promising lead structure. In the ADP-Glo assay, it was determined that this compound exhibits a 5.96±1.66 μM IC50 value (Table 1), after which the effect of replacing the CF3 with an SF5-group at the C-5 position as shown for compound 13 was explored. The ADP-Glo assay can be conducted as described in Chou, T.-F.; Bulfer, S. L.; Weihl, C. C.; Li, K.; Lis, L. G.; Walters, M. A.; Schoenen, F. J.; Lin, H. J.; Deshaies, R. J.; Arkin, M. R., Specific inhibition of p97/VCP atpase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains. J. Mol. Biol. 2014, 426, 2886-2899.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 475.66, ALogP 4.7, HBA 4, HBD 2, PSA 37.54, QED 0.54
Compound (SMILES): Cc1nc2ccc(Br)cc2c(-c2ccc(Cl)cc2)c1C(OC(C)(C)C)C(=O)O
InChIKey: UXIVWMINNPGARX-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of LEDGF/p75 binding to HIV1 His/FLAG-tagged integrase expressed in Escherichia coli BL21(DE3) by HTRF assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 462.77, ALogP 6.57, HBA 3, HBD 1, PSA 59.42, QED 0.48
Compound (SMILES): FC1(F)CC[C@H](Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: PDXMOPYZKDLAPA-NSHDSACASA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 505.37, ALogP 5.71, HBA 7, HBD 2, PSA 88.51, QED 0.43
Compound (SMILES): CNc1ncc(C(=O)NNc2ccccc2)c2nc(-c3ccco3)nn12
InChIKey: REOHRGISVBVLES-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 349.35, ALogP 2.18, HBA 8, HBD 3, PSA 109.38, QED 0.47
Compound (SMILES): COc1cccc(-c2ccc(Nc3cc(=O)n(O)c(=O)[nH]3)cc2)c1
InChIKey: PAYHGQLCBWRTFD-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of re-constituted HIV1 reverse transcriptase RNase H domain fragment
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 325.32, ALogP 2.19, HBA 6, HBD 3, PSA 96.35, QED 0.64
Compound (SMILES): C[C@H]1O[C@@H]2C[C@](O)([C@H]1O)n1c3ccccc3c3c4c(c5c6cc(O)ccc6n2c5c31)C(=O)NC4
InChIKey: NEPZGORZKOUWMU-BWNIXSQGSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKCtheta (unknown origin) by HTRF assay
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 455.47, ALogP 3.18, HBA 7, HBD 4, PSA 108.88, QED 0.29
Compound (SMILES): Cc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: DBNRSQHWQKIXGR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 203.2, ALogP 1.27, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): CCCN1CC(=O)N2Cc3c(c4ccccc4n3Cc3ccc(C(=O)NO)cc3)CC2C1=O
InChIKey: WKWJMPGMWAQUAL-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human recombinant HDAC4 using fluorogenic trifluoroacetyl lysine as substrate by fluorescence assay
Measurement: IC50 = 20500 nM (pChEMBL 4.690000057220459)
Descriptors: MW 446.51, ALogP 2.31, HBA 5, HBD 2, PSA 94.88, QED 0.46