lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(c1ccccc1)c1ccc2n1CCC2C(=O)NCCOc1ccc2oc(=O)ccc2c1
InChIKey: HREFIMOFGJMXJB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 catalytic domain preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 31.8 nM (pChEMBL 7.5)
Descriptors: MW 442.47, ALogP 3.51, HBA 6, HBD 1, PSA 90.54, QED 0.27
Compound (SMILES): O=Cc1cnn2ccc(NC(=O)CCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc12
InChIKey: PMBZPLQKUNCRDH-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]spiperone from human Dopamine D4 receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 460.37, ALogP 3.99, HBA 6, HBD 1, PSA 69.95, QED 0.54
Compound (SMILES): Cc1ccc(-c2cc3c(N[C@@H]4CC[C@](C)(N)C4(C)C)c(C(N)=O)cnn3c2)cn1
InChIKey: YLPRMWFQNIEVDO-GCJKJVERSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2 induced IFN-gamma production after 18 hrs by ELISA
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 392.51, ALogP 3.12, HBA 6, HBD 3, PSA 111.33, QED 0.63
Compound (SMILES): COc1cc(C)[nH]c(=O)c1CN1CCc2c(Cl)cc(C(OC)C3CCOC3)c(Cl)c2C1=O
InChIKey: AZFROWZIMGUVBM-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 in human KARPAS422 cells assessed as reduction in H3K27me3 level after 72 hrs by ELISA
Measurement: IC50 = 391 nM (pChEMBL 6.409999847412109)
Descriptors: MW 481.38, ALogP 3.92, HBA 5, HBD 1, PSA 80.86, QED 0.68
Compound (SMILES): COc1ccccc1N1CCN(CCCCOc2ccn3ncc(/C=N/O)c3c2)CC1
InChIKey: BZCYPHOOPXOADD-XIEYBQDHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]spiperone from human Dopamine D2S receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 0.72 nM (pChEMBL 9.140000343322754)
Descriptors: MW 423.52, ALogP 3.13, HBA 8, HBD 1, PSA 74.83, QED 0.25
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)Nc3cncc(C(=O)O)c3)[nH]c3c(-c4c(C)nn(C)c4C)c(Cl)ccc23)cc(C)c1Cl
InChIKey: UJBDBUQHMJYLGN-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki = 61500 nM (pChEMBL 4.210000038146973)
Descriptors: MW 620.54, ALogP 7.47, HBA 6, HBD 3, PSA 122.13, QED 0.15
Compound (SMILES): Cc1ccc(-c2cc3c(N[C@@H]4CC[C@](C)(N)C4(C)C)c(C(N)=O)cnn3c2)cc1
InChIKey: RKRKQDQJBAZLNK-XXBNENTESA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2 induced IFN-gamma production after 18 hrs by ELISA
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 391.52, ALogP 3.73, HBA 5, HBD 3, PSA 98.44, QED 0.63
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(N4CCN(C)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: JJFZFULVGZVWGT-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Lantha Screen Eu Kinase Activity Assay: The effects of compounds on the kinases DDR1 and DDR2 were assessed by using a Lantha Screen Eu kinase activity assay technology (Invitrogen, USA). Kinase reactions are performed in a 10 uL volume in low-volume 384-well plates. The kinases in reaction buffer consist of 50 mM HEPES pH 7.5, 0.01% BRU-35, 10 mM MgCl2, and 1 mM EGTA, the concentration of Fluorescein-Poly GAT substrate (Invitrogen, USA) in the assay is 100 nM. Kinase reactions were initiated with the addition of 100 nM ATP in the presence of serials of dilutions of compounds. The reactions were allowed to proceed for 1 h at room temperature before a 10 uL preparation of EDTA (20 mM) and Eu-labeled antibody (4 nM) in TR-FRET dilution buffer are added. The final concentration of antibody in the assay well is 2 nM, and the final concentration of EDTA is 10 mM. The plate is allowed to incubate at room temperature for one more hour before the TR-FRET emission ratios of 665 nm/340 nm were acquired on a PerkinElmer EnVision multilabel reader (Perkin-Elmer, Inc.). Data analysis and curve fitting were performed using GraphPad Prism4 software, resulting in the half maximal inhibitory concentration (IC50) shown in table 1. The functional assays of compounds on the kinase activities of c-kit and Abl were determined using the FRET-based Z'-Lyte assay system according to the manufacturer's instructions (Invitrogen, USA). Tyrosine 2 peptide was used as Abl substrate, and Ser/Thr 6 peptide was used as the substrate for c-kit. The reactions were carried out in 384-well plates in a 10 uL of reaction volume with appropriate amount of kinases in 50 mM HEPES (pH 7.5), 10 Mm MgCl2, 1 mM EGTA, and 0.01% Brij-35. The reactions were incubated 1 h at room temperature in the presence of 2 uM of substrate with 10 uM of ATP (for Abl1 assays) or 300 uM of ATP (kit assay) and in the presence of various concentrations of the compounds.
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 510.56, ALogP 4.62, HBA 6, HBD 1, PSA 64.6, QED 0.55
Compound (SMILES): O=C(c1ccccc1)N1CCc2oc(-c3ccc(F)cn3)nc2C1
InChIKey: FOPJMYBQTFPHTL-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 323.33, ALogP 3.07, HBA 4, HBD 0, PSA 59.23, QED 0.73
Compound (SMILES): N[C@@]1(C(=O)O)C[C@H](NC(=O)C2CCCCC2)[C@H]2[C@H](C(=O)O)[C@H]21
InChIKey: URPILZHDNHGJFA-DMZJWBPISA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Agonist activity at human mGlu2 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay
Measurement: EC50 = 3390 nM (pChEMBL 5.46999979019165)
Descriptors: MW 310.35, ALogP 0.18, HBA 4, HBD 4, PSA 129.72, QED 0.59
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)c(F)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12
InChIKey: HNKNKWOBIYGMKR-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK293 cells assessed as reduction in peak inward current by ionworks quattro electrophysiology assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 543.5, ALogP 6.52, HBA 6, HBD 1, PSA 94.32, QED 0.25
Compound (SMILES): COC[C@@H](NC(=O)N1CC(=O)Nc2cc(OC)cnc21)c1ccc(OC(F)(F)F)c(F)c1
InChIKey: AWJSRXUQLSPAOI-CQSZACIVSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PDE5A1 expressed in baculovirus infected fall armyworm Sf9 cells using [3H]cGMP as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by scintillation counting
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 458.37, ALogP 2.98, HBA 6, HBD 2, PSA 102.02, QED 0.65
Compound (SMILES): O=C(C(=S)N1CCOCC1)c1ccc(F)cc1
InChIKey: LQWLWWYWWKQSBQ-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH in human HL60 cells assessed as reduction in cell viability in serine depleted medium after 5 days by presto blue assay
Measurement: IC50 = 64400 nM (pChEMBL 4.190000057220459)
Descriptors: MW 253.3, ALogP 1.67, HBA 3, HBD 0, PSA 29.54, QED 0.59
Compound (SMILES): Cc1cccc(S(=O)(=O)NCCCN2CC=C(c3c[nH]c4ccc(F)cc34)CC2)c1
InChIKey: DCQKCNGVYBRKSC-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from human D2 receptor expressed in CHO-K1 cells after 60 mins by scintillation counting
Measurement: Ki = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 427.55, ALogP 4.07, HBA 3, HBD 2, PSA 65.2, QED 0.56
Compound (SMILES): COc1ccc(-c2ccc(Oc3cccc4c3CCCC4)c(NC(=O)Nc3cccc(C)c3)c2)cc1C(=O)O
InChIKey: SSUQEFNUCUXHQL-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 522.6, ALogP 7.68, HBA 4, HBD 3, PSA 96.89, QED 0.23
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cccc(C#N)c3)CC2)nc2ccsc12
InChIKey: MWXHRAPYPDVMJW-QPJJXVBHSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase E138K mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 27.9 nM (pChEMBL 7.550000190734863)
Descriptors: MW 520.66, ALogP 6.59, HBA 8, HBD 1, PSA 97.86, QED 0.27
Compound (SMILES): Cc1csc2cc([C@H](C)Nc3ncnc(N)c3C#N)c(Cc3cccc(CNCCCCOCCc4ccccc4)c3)c(=O)n12
InChIKey: RHJYRDFGTODYSM-VWLOTQADSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human JeKo1 cells assessed as reduction in Akt phosphorylation at Ser473 residue preincubated for 60 mins followed by Anti-IgM stimulation for 10 mins by TR-FRET assay
Measurement: IC50 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 621.81, ALogP 5.81, HBA 10, HBD 3, PSA 130.36, QED 0.13
Compound (SMILES): Nc1nccn2c([C@H]3CN(C4CCOCC4)CCO3)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3F)c12
InChIKey: GZYUJXFTHLKPAK-OAQYLSRUSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant full-length His6-tagged BTK (unknown origin) expressed in baculovirus infected Sf9 cells using biotinylated A5 peptide as substrate preincubated for 60 mins followed by substrate addition measured after 120 mins by LANCE TR-FRET assay
Measurement: IC50 = 0.59 nM (pChEMBL 9.229999542236328)
Descriptors: MW 585.56, ALogP 4.34, HBA 9, HBD 2, PSA 119.9, QED 0.33
Compound (SMILES): O=C(c1cc([C@H]2CCCN2c2cc(F)cc(F)c2)c2oc(N3CCOCC3)cc(=O)c2c1)N1CCOCC1
InChIKey: CPFXYHKMOTWOFK-XMMPIXPASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3Kdelta using PIP2 as substrate preincubated for 20 mins followed by substrate addition measured after 80 mins in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 525.55, ALogP 3.72, HBA 7, HBD 0, PSA 75.46, QED 0.51
Compound (SMILES): Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: GCXKULANKFAPOX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 225 nM (pChEMBL 6.650000095367432)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): COc1ccc(S(=O)(=O)N(C(C)=O)c2ccccc2/C=C/c2cc[n+]([O-])cc2)cc1
InChIKey: OCKHRKSTDPOHEN-BQYQJAHWSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.48, ALogP 3.24, HBA 5, HBD 0, PSA 90.62, QED 0.45
Compound (SMILES): CCS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1.Cl
InChIKey: IYULGYKOHUAYCG-UHFFFAOYSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 445.55, ALogP 1.37, HBA 8, HBD 3, PSA 133.55, QED 0.55
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: KSUDUUBCXJUFRL-SFHVURJKSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 456.51, ALogP 3.31, HBA 8, HBD 1, PSA 108.27, QED 0.46
Compound (SMILES): Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)NCc2cc(F)ccc2Oc2ccc3c(cnn3CCO)c2)cc1
InChIKey: LNMRSSIMGCDUTP-UHFFFAOYSA-N
Target: Peroxisomal acyl-coenzyme A oxidase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15254
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 556.64, ALogP 6.07, HBA 7, HBD 3, PSA 106.23, QED 0.22
Compound (SMILES): Cc1nc2cc(-c3nn(C(C)C)c4ncnc(N)c34)ccc2o1
InChIKey: JUUFLLKHNYWHKP-UHFFFAOYSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 308.35, ALogP 3.11, HBA 7, HBD 1, PSA 95.65, QED 0.61
Compound (SMILES): COCc1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)c2c(N)ncnn2c1CN1CCOCC1
InChIKey: GZPJCJKUZPUFAL-UHFFFAOYSA-N
Target: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P49748
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.54, ALogP 4.9, HBA 8, HBD 3, PSA 119.04, QED 0.26
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@@H]1CO.Cl
InChIKey: OOVTUOCTLAERQD-OJMBIDBESA-N
Target: Peroxisomal acyl-coenzyme A oxidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15067
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 401.85, ALogP 3.3, HBA 6, HBD 3, PSA 94.14, QED 0.62
Compound (SMILES): CN(C)c1nc2ccc(C(O)(c3ccncc3)c3cncn3C)cc2c(Cl)c1-c1ccccc1
InChIKey: SEJAMGYPDDPTHR-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4 DBD-fused human RORgammat expressed in HEK293T cells assessed as inhibition of transcriptional activity after 24 hrs by Dual-glo luciferase reporter gene assay
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 469.98, ALogP 5.03, HBA 6, HBD 1, PSA 67.07, QED 0.39
Compound (SMILES): CCc1cc2cc(NS(=O)(=O)c3ccc(C#N)cc3)ccc2n(CC)c1=O
InChIKey: QTIVTZLLONAWRR-UHFFFAOYSA-N
Target: TATA box-binding protein-associated factor RNA polymerase I subunit A (SINGLE PROTEIN), Homo sapiens
UniProt: Q15573
Assay: Inhibition of human His tagged TAF1A incubated for 30 mins followed by addition of biotinylated peptide and further incubation for 30 mins measured by AlphaScreen assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 381.46, ALogP 3.26, HBA 5, HBD 1, PSA 91.96, QED 0.73
Compound (SMILES): CCCN[C@@H]1Cc2cccc3c2n(c(=O)n3CCCCOCCCCc2ccccc2)C1
InChIKey: HMBLGIYYEVWFCT-XMMPIXPASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Agonist activity at human dopamine D2 receptor expressed in HEK293 cells coexpressing renilla luciferase-fused GalphaoA/GFP10-fused Ggamma2 by BRET assay
Measurement: EC50 = 24.6 nM (pChEMBL 7.610000133514404)
Descriptors: MW 435.61, ALogP 4.55, HBA 5, HBD 1, PSA 48.19, QED 0.4
Compound (SMILES): O=C(/C=C/c1ccc2ccccc2c1)c1cccnc1
InChIKey: VWBDGXJRQZDLRV-CSKARUKUSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver CYP2C9 expressed in Saccharomyces cerevisiae YY7 microsomal membranes using DBF as substrate after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 259.31, ALogP 4.13, HBA 2, HBD 0, PSA 29.96, QED 0.52
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cccnc3)CC2)nc2ccsc12
InChIKey: RTUZYZMEIYLNIT-HWKANZROSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase F227L/V106A double mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 5.82 nM (pChEMBL 8.229999542236328)
Descriptors: MW 496.64, ALogP 6.11, HBA 8, HBD 1, PSA 86.96, QED 0.31
Compound (SMILES): CCC(=O)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1
InChIKey: SADFFAQSWHTWLL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human muscarinic acetylcholine receptor M2 expressed in CHOK9 cells after 3 hrs by liquid scintillation counting assay
Measurement: Ki = 0.7586 nM (pChEMBL 9.119999885559082)
Descriptors: MW 627.79, ALogP 4.27, HBA 7, HBD 3, PSA 128.67, QED 0.23
Compound (SMILES): O=C1SCCc2nc(-c3ccc(C(F)(F)F)cc3)[nH]c(=O)c21
InChIKey: YAAIOGGCMLWOPM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of recombinant human N-terminal GST-tagged TNKS1 (1001 to 1327 residues) expressed in baculovirus infected sf9 cells using TACS-Sapphire as substrate measured after 30 mins by colorimetric assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 326.3, ALogP 2.89, HBA 4, HBD 1, PSA 62.82, QED 0.88
Compound (SMILES): O=C(C1CCN(c2cc(Oc3ccc(F)cc3F)ncn2)CC1)N1CCc2ccccc2C1
InChIKey: RGKNMWKLNOOSDH-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from recombinant human M4 receptor expressed in CHO cell membranes
Measurement: Ki = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 450.49, ALogP 4.35, HBA 5, HBD 0, PSA 58.56, QED 0.59
Compound (SMILES): CC[C@@H](NC(=O)c1cnn2cc(C)cnc12)c1ccc(OC(F)(F)F)cc1
InChIKey: CXEGBNQZVKLHTO-OAHLLOKOSA-N
Target: Rod cGMP-specific 3',5'-cyclic phosphodiesterase alpha/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P35913
Assay: Inhibition of recombinant human PDE6A/PDE6B expressed in baculovirus infected Sf9 cell expression system using [3H]cGMP as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by scintillation proximity assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 378.35, ALogP 3.82, HBA 5, HBD 1, PSA 68.52, QED 0.73
Compound (SMILES): CC(=O)N1CCN(c2cccc(-c3cc(-c4ccnn4CC(F)(F)F)c4c(N)ncnn34)c2)C(=O)C1(C)C
InChIKey: KSAKMNJFOKNIAA-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 526.52, ALogP 3.38, HBA 8, HBD 1, PSA 114.65, QED 0.44
Compound (SMILES): CCn1nnc([C@H]2O[C@@H](n3cnc4c(NCc5cccc(Br)c5)nc(Cl)nc43)[C@H](O)[C@@H]2O)n1
InChIKey: WTSRCKFFAWSKBH-MOROJQBDSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at recombinant human adenosine A2B receptor expressed in CHO cell membranes assessed as stimulation of adenylyl cyclase activity by [alpha-32P]ATP assay
Measurement: EC50 = 1650 nM (pChEMBL 5.78000020980835)
Descriptors: MW 536.78, ALogP 1.85, HBA 12, HBD 3, PSA 148.92, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccccc3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1
InChIKey: YECANFWMOCZDPE-UHFFFAOYSA-N
Target: L-lactate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: V9HWB9
Assay: Inhibition of LDH in human MIAPaCa2 cells assessed as reduction in lactate production preincubated for 2 hrs measured after 30 mins by high throughput fluorescence assay
Measurement: IC50 = 5120 nM (pChEMBL 5.289999961853027)
Descriptors: MW 494.6, ALogP 3.88, HBA 7, HBD 2, PSA 128.17, QED 0.38
Compound (SMILES): CC(=O)N[C@H]1CSCc2cc3cc(c2)CSC[C@H](C(=O)N[C@@H](C)C(=O)N(C)CC(=O)N(C)CC(=O)N(C)CC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2c[nH]c4ccccc24)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CSC3)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: OHOYFNPMBCNOTR-QFZQKJJLSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of recombinant human plasmin using fluorogenic D-AFK-ANSNH-iC4H9.2HBr peptide as substrate by fluorescence based assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 2558.96
Compound (SMILES): CC1(N)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1
InChIKey: YGUFCDOEKKVKJK-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of recombinant human SHP2 PTP domain (237 to 535 residues) using DiFMUP as substrate preincubated for 30 mins and followed by substrate addition and measured by microplate reader method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.27, ALogP 3.35, HBA 5, HBD 2, PSA 81.06, QED 0.87
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3cc(-c4cccc5ccccc45)ccc23)c(OC)cc1N(C)CCN(C)C
InChIKey: OYXSSEAGSFYOGN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant in human NCI-H1975 cells assessed as reduction in cell viability after 96 hrs by CellTiterGlo assay
Measurement: EC50 = 1102 nM (pChEMBL 5.960000038146973)
Descriptors: MW 534.66, ALogP 6.26, HBA 6, HBD 3, PSA 85.52, QED 0.18
Compound (SMILES): COc1ccc(-c2ccc(Oc3cccc4c3CCCC4)c(NC(=O)Nc3ccccc3Cl)c2)cc1C(=O)O
InChIKey: OLUVZKHXNIKBIS-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BZR as substrate
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 543.02, ALogP 8.03, HBA 4, HBD 3, PSA 96.89, QED 0.22
Compound (SMILES): C=CC(=O)Nc1cc(Nc2n[nH]c3cc(-c4ccc(F)cc4)ccc23)c(OC)cc1N(C)CCN(C)C
InChIKey: BUVGSBCMNREXAL-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant in human NCI-H1975 cells assessed as reduction in cell viability after 96 hrs by CellTiterGlo assay
Measurement: EC50 = 659 nM (pChEMBL 6.179999828338623)
Descriptors: MW 502.59, ALogP 5.24, HBA 6, HBD 3, PSA 85.52, QED 0.26
Compound (SMILES): Cn1cnc(C(=O)N2CCN(C(=O)c3ccc(Nc4nc5ccccc5n5nnnc45)cc3)CC2)c1
InChIKey: YFNNDVKJUPAWSW-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP16 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N5Y8
Assay: Binding affinity to PARP16 in human Jurkat cell extract after 45 mins by mass spectrometric analysis
Measurement: IC50 > 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 482.51, ALogP 1.75, HBA 10, HBD 1, PSA 126.44, QED 0.41
Compound (SMILES): CNC(=O)[C@H](NC(=O)c1ccc(-c2ccc(CSc3nc4c(c(=O)[nH]3)CCC4)c(F)c2)o1)C1CCCCC1
InChIKey: VAUVOKSOLZDEJH-XMMPIXPASA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of recombinant human MMP14 using fTHP-15 as substrate preincubated for 30 mins followed by substrate addition measured immediately by fluorescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 538.65, ALogP 4.37, HBA 6, HBD 3, PSA 117.09, QED 0.29
Compound (SMILES): O=C(CCCCCCn1cc(-c2ncnc3[nH]ccc23)cn1)NO
InChIKey: YRRVLBINSXVLFM-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in Baculovirus infected insect cells in presence of ATP
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 328.38, ALogP 2.28, HBA 6, HBD 3, PSA 108.72, QED 0.33
Compound (SMILES): CCNC(=O)c1noc(-c2cc(Cl)c(O)cc2O)c1-c1ccc(CN2CCOCC2)cc1C
InChIKey: RXSXHCNTLOATRW-UHFFFAOYSA-N
Target: ATP-dependent molecular chaperone HSP82 (SINGLE PROTEIN), Saccharomyces cerevisiae S288c
UniProt: P02829
Assay: Fluorescence Polarization Assay: 1) Costar 96-well black assay plate. Assay buffer of (a) 100 mM Tris pH7.4; (b) 20 mM KCl; (c) 6 mM MgCl2. Stored at room temperature.3) BSA (bovine serum albumen) 10 mg/ml (New England Biolabs # B9001S)4) 20 mM probe in 100% DMSO stock concentration. Stored in the dark at RT. Working concentration is 200 nM diluted in AR water and stored at 4Â° C. Final concentration in assay 80 nM.5) E. coli expressed human full-length HSP90 protein, purified>95% (see, e.g., Panaretou et al., 1998) and stored in 50 uL aliquots at C. Protocol: 1) Add 100 ul buffer to wells 11A and 12A (=FP BLNK)2) Prepare assay reagents are kept on ice with a lid on the bucket as the probe is light-sensitive. i. Final Conc Hsp90 FP Buffer 10 ml 1xBSA 10 mg/ml (NEB) 5.0 ul 5 ug/ml Probe 200 uM 4.0 ul 80 nM Human full-length Hsp90 6.25 ul 200 nM 3) Aliquot 100 ul assay mix to all other wells 4) Seal plate and leave in dark at room temp for 20 minutes to equilibrate. Compound Dilution Plate 1x3 Dilution Series1) In a clear 96-well v-bottom plate {# VWR 007/008/257} add 10 ul 100% DMSO to wells B1 to H112) To wells A1 to A11 add 17.5 ul 100% DMSO 3) Add 2.5 ul cpd to A1. This gives 2.5 mM {50x} stock cpd assuming cpds 20 mM. 4) Repeat for wells A2 to A10. Control in columns 11 and 12.5) Transfer 5 ul from row A to row B-not column 12. Mix well.6) Transfer 5 ul from row B to row C. Mix well.7) Repeat to row G. 8) Do not add any compound to row H-this is the 0 row. 9) This produces a 1x3 dilution series from 50 uM to 0.07 uM.10) In well B12 prepare 20 ul of 100 uM standard compound. 11) After first incubation the assay plate is read on a Fusion a-FP plate reader. 12) After the first read, 2 ul of diluted compound is added to each well for columns 1 to 10. In column 11 {provides standard curve} only add compound B11-H11. Add 2 ul of 100 mM standard cpd to wells B12-H12 {is positive control} 13) The Zâ factor is calculated from zero controls and positive wells. It typically gives a value of 0.7-0.9.
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 471.94, ALogP 3.96, HBA 7, HBD 3, PSA 108.06, QED 0.5
Compound (SMILES): O=C(O)CC1CCC2(CCN(c3ccc(-c4nc5cc(C(F)(F)F)ccc5[nH]4)cn3)CC2)OC1
InChIKey: LFHXTDBDALXSLW-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 25600 nM (pChEMBL 4.590000152587891)
Descriptors: MW 474.48, ALogP 4.88, HBA 5, HBD 2, PSA 91.34, QED 0.56
Compound (SMILES): N[C@@H](CCP(=O)(O)C(O)c1ccc(O)c([N+](=O)[O-])c1)C(=O)O
InChIKey: GAGSUJFFXBSIDN-RGENBBCFSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Agonist activity at mGlu4 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 334.22, ALogP 0.36, HBA 7, HBD 5, PSA 184.22, QED 0.27
Compound (SMILES): O=C(NC1CCN(Cc2ccccc2)CC1)c1ccc(Cl)nc1Cl
InChIKey: FGUUNZVMTXKKDT-UHFFFAOYSA-N
Target: Sodium- and chloride-dependent betaine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P48065
Assay: Inhibition of human BGT1 Q299L mutant expressed in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 364.28, ALogP 3.78, HBA 3, HBD 1, PSA 45.23, QED 0.84
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CS)C(N)=O
InChIKey: RQZHKEFEFWSLOK-PHNIDTBTSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in low doxycyclin-treated HEK293 cell membranes assessed as increase in cAMP production after 45 mins by HTRF method
Measurement: EC50 = 0.6918 nM (pChEMBL 9.15999984741211)
Descriptors: MW 1119.35
Compound (SMILES): O=C(c1ccccc1)c1ccc2n1CCC2C(=O)NCCOc1ccc2oc(=O)ccc2c1
InChIKey: HREFIMOFGJMXJB-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 442.47, ALogP 3.51, HBA 6, HBD 1, PSA 90.54, QED 0.27
Compound (SMILES): O=Cc1cnn2ccc(NC(=O)CCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc12
InChIKey: PMBZPLQKUNCRDH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]ketanserin from human 5-HT2A receptor expressed in HEK293T cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 460.37, ALogP 3.99, HBA 6, HBD 1, PSA 69.95, QED 0.54
Compound (SMILES): Cc1ccc(-c2cc3c(N[C@@H]4CC[C@](C)(N)C4(C)C)c(C(N)=O)cnn3c2)cn1
InChIKey: YLPRMWFQNIEVDO-GCJKJVERSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by flux-based assay
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 392.51, ALogP 3.12, HBA 6, HBD 3, PSA 111.33, QED 0.63
Compound (SMILES): COc1cc(C)[nH]c(=O)c1CN1CCc2c(Cl)cc(C(OC)C3CCOC3)c(Cl)c2C1=O
InChIKey: AZFROWZIMGUVBM-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 in human KARPAS422 cells assessed as reduction in H3K27me3 level after 72 hrs by ELISA
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 481.38, ALogP 3.92, HBA 5, HBD 1, PSA 80.86, QED 0.68
Compound (SMILES): COc1ccccc1N1CCN(CCCCOc2ccn3ncc(/C=N/O)c3c2)CC1
InChIKey: BZCYPHOOPXOADD-XIEYBQDHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]spiperone from human Dopamine D2S receptor expressed in CHO cell membranes after 2 hrs by scintillation counting analysis
Measurement: Ki = 0.094 nM (pChEMBL 10.029999732971191)
Descriptors: MW 423.52, ALogP 3.13, HBA 8, HBD 1, PSA 74.83, QED 0.25
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)Nc3cncc(C(=O)O)c3)[nH]c3c(-c4c(C)nn(C)c4C)c(Cl)ccc23)cc(C)c1Cl
InChIKey: UJBDBUQHMJYLGN-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki = 3200 nM (pChEMBL 5.5)
Descriptors: MW 620.54, ALogP 7.47, HBA 6, HBD 3, PSA 122.13, QED 0.15
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cc(N4CCN(C)CC4)cc(C(F)(F)F)c3)ccc21
InChIKey: JJFZFULVGZVWGT-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Lantha Screen Eu Kinase Activity Assay: The effects of compounds on the kinases DDR1 and DDR2 were assessed by using a Lantha Screen Eu kinase activity assay technology (Invitrogen, USA). Kinase reactions are performed in a 10 uL volume in low-volume 384-well plates. The kinases in reaction buffer consist of 50 mM HEPES pH 7.5, 0.01% BRU-35, 10 mM MgCl2, and 1 mM EGTA, the concentration of Fluorescein-Poly GAT substrate (Invitrogen, USA) in the assay is 100 nM. Kinase reactions were initiated with the addition of 100 nM ATP in the presence of serials of dilutions of compounds. The reactions were allowed to proceed for 1 h at room temperature before a 10 uL preparation of EDTA (20 mM) and Eu-labeled antibody (4 nM) in TR-FRET dilution buffer are added. The final concentration of antibody in the assay well is 2 nM, and the final concentration of EDTA is 10 mM. The plate is allowed to incubate at room temperature for one more hour before the TR-FRET emission ratios of 665 nm/340 nm were acquired on a PerkinElmer EnVision multilabel reader (Perkin-Elmer, Inc.). Data analysis and curve fitting were performed using GraphPad Prism4 software, resulting in the half maximal inhibitory concentration (IC50) shown in table 1. The functional assays of compounds on the kinase activities of c-kit and Abl were determined using the FRET-based Z'-Lyte assay system according to the manufacturer's instructions (Invitrogen, USA). Tyrosine 2 peptide was used as Abl substrate, and Ser/Thr 6 peptide was used as the substrate for c-kit. The reactions were carried out in 384-well plates in a 10 uL of reaction volume with appropriate amount of kinases in 50 mM HEPES (pH 7.5), 10 Mm MgCl2, 1 mM EGTA, and 0.01% Brij-35. The reactions were incubated 1 h at room temperature in the presence of 2 uM of substrate with 10 uM of ATP (for Abl1 assays) or 300 uM of ATP (kit assay) and in the presence of various concentrations of the compounds.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 510.56, ALogP 4.62, HBA 6, HBD 1, PSA 64.6, QED 0.55
Compound (SMILES): O=C(c1ccccc1)N1CCc2oc(-c3ccc(F)cn3)nc2C1
InChIKey: FOPJMYBQTFPHTL-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using (S)-mephenytoin as substrate after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 323.33, ALogP 3.07, HBA 4, HBD 0, PSA 59.23, QED 0.73
Compound (SMILES): N[C@@]1(C(=O)O)C[C@H](NC(=O)C2CCCCC2)[C@H]2[C@H](C(=O)O)[C@H]21
InChIKey: URPILZHDNHGJFA-DMZJWBPISA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Antagonist activity at human mGlu3 receptor expressed in HEK cells assessed as reversal of DCG-4 inhibited forskolin-stimulated cAMP formation after 20 mins by HTRF assay
Measurement: IC50 = 9990 nM (pChEMBL 5)
Descriptors: MW 310.35, ALogP 0.18, HBA 4, HBD 4, PSA 129.72, QED 0.59
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)c(F)cc1-c1nccc2cc(S(=O)(=O)Nc3ccon3)ccc12
InChIKey: HNKNKWOBIYGMKR-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells assessed as reduction in peak inward current by ionworks quattro electrophysiology assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 543.5, ALogP 6.52, HBA 6, HBD 1, PSA 94.32, QED 0.25
Compound (SMILES): COC[C@@H](NC(=O)N1CC(=O)Nc2cc(OC)cnc21)c1ccc(OC(F)(F)F)c(F)c1
InChIKey: AWJSRXUQLSPAOI-CQSZACIVSA-N
Target: Rod cGMP-specific 3',5'-cyclic phosphodiesterase alpha/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P35913
Assay: Inhibition of recombinant human PDE6A/PDE6B expressed in insect cells using [3H]cGMP as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by scintillation counting
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 458.37, ALogP 2.98, HBA 6, HBD 2, PSA 102.02, QED 0.65
Compound (SMILES): COc1ccc(-c2ccc(Oc3cccc4c3CCCC4)c(NC(=O)Nc3cccc(C)c3)c2)cc1C(=O)O
InChIKey: SSUQEFNUCUXHQL-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BZR as substrate
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 522.6, ALogP 7.68, HBA 4, HBD 3, PSA 96.89, QED 0.23
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cccc(C#N)c3)CC2)nc2ccsc12
InChIKey: MWXHRAPYPDVMJW-QPJJXVBHSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase F227L/V106A double mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 26.3 nM (pChEMBL 7.579999923706055)
Descriptors: MW 520.66, ALogP 6.59, HBA 8, HBD 1, PSA 97.86, QED 0.27
Compound (SMILES): Nc1nccn2c([C@H]3CN(C4CCOCC4)CCO3)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3F)c12
InChIKey: GZYUJXFTHLKPAK-OAQYLSRUSA-N
Target: Tyrosine-protein kinase CSK (SINGLE PROTEIN), Homo sapiens
UniProt: P41240
Assay: Inhibition of CSK (unknown origin)
Measurement: IC50 = 665 nM (pChEMBL 6.179999828338623)
Descriptors: MW 585.56, ALogP 4.34, HBA 9, HBD 2, PSA 119.9, QED 0.33
Compound (SMILES): O=C(c1cc([C@H]2CCCN2c2cc(F)cc(F)c2)c2oc(N3CCOCC3)cc(=O)c2c1)N1CCOCC1
InChIKey: CPFXYHKMOTWOFK-XMMPIXPASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Mus musculus
UniProt: Q9JHG7
Assay: Inhibition of PI3Kgamma in mouse RAW264 cells assessed as decrease in AKT phosphorylation at Ser473
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 525.55, ALogP 3.72, HBA 7, HBD 0, PSA 75.46, QED 0.51
Compound (SMILES): Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: GCXKULANKFAPOX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): COc1ccc(S(=O)(=O)N(C(C)=O)c2ccccc2/C=C/c2cc[n+]([O-])cc2)cc1
InChIKey: OCKHRKSTDPOHEN-BQYQJAHWSA-N
Target: Peroxisomal acyl-coenzyme A oxidase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15254
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 424.48, ALogP 3.24, HBA 5, HBD 0, PSA 90.62, QED 0.45
Compound (SMILES): CCS(=O)(=O)N1CCN(c2ccc(Nc3ncc(C(N)=O)c(NC4CC4)n3)cc2)CC1.Cl
InChIKey: IYULGYKOHUAYCG-UHFFFAOYSA-N
Target: Peroxisomal acyl-coenzyme A oxidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15067
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 445.55, ALogP 1.37, HBA 8, HBD 3, PSA 133.55, QED 0.55
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2c(=O)n(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
InChIKey: KSUDUUBCXJUFRL-SFHVURJKSA-N
Target: Peroxisomal acyl-coenzyme A oxidase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15254
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 456.51, ALogP 3.31, HBA 8, HBD 1, PSA 108.27, QED 0.46
Compound (SMILES): Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)NCc2cc(F)ccc2Oc2ccc3c(cnn3CCO)c2)cc1
InChIKey: LNMRSSIMGCDUTP-UHFFFAOYSA-N
Target: Long-chain-fatty-acid--CoA ligase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULC5
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 556.64, ALogP 6.07, HBA 7, HBD 3, PSA 106.23, QED 0.22
Compound (SMILES): Cc1nc2cc(-c3nn(C(C)C)c4ncnc(N)c34)ccc2o1
InChIKey: JUUFLLKHNYWHKP-UHFFFAOYSA-N
Target: Peroxisomal acyl-coenzyme A oxidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15067
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 308.35, ALogP 3.11, HBA 7, HBD 1, PSA 95.65, QED 0.61
Compound (SMILES): COCc1c(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)c2c(N)ncnn2c1CN1CCOCC1
InChIKey: GZPJCJKUZPUFAL-UHFFFAOYSA-N
Target: Peroxisomal acyl-coenzyme A oxidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15067
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 591.54, ALogP 4.9, HBA 8, HBD 3, PSA 119.04, QED 0.26
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@@H]1CO.Cl
InChIKey: OOVTUOCTLAERQD-OJMBIDBESA-N
Target: Peroxisomal acyl-coenzyme A oxidase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15254
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 401.85, ALogP 3.3, HBA 6, HBD 3, PSA 94.14, QED 0.62
Compound (SMILES): CCc1cc2cc(NS(=O)(=O)c3ccc(C#N)cc3)ccc2n(CC)c1=O
InChIKey: QTIVTZLLONAWRR-UHFFFAOYSA-N
Target: Nucleosome-remodeling factor subunit BPTF (SINGLE PROTEIN), Homo sapiens
UniProt: Q12830
Assay: Inhibition of human His tagged FALZ incubated for 30 mins followed by addition of biotinylated peptide and further incubation for 30 mins measured by AlphaScreen assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 381.46, ALogP 3.26, HBA 5, HBD 1, PSA 91.96, QED 0.73
Compound (SMILES): O=C(/C=C/c1ccc2ccccc2c1)c1cccnc1
InChIKey: VWBDGXJRQZDLRV-CSKARUKUSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human liver CYP2C19 expressed in Saccharomyces cerevisiae YY7 microsomal membranes using DBF as substrate after 10 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 259.31, ALogP 4.13, HBA 2, HBD 0, PSA 29.96, QED 0.52
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cccnc3)CC2)nc2ccsc12
InChIKey: RTUZYZMEIYLNIT-HWKANZROSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 RES056 reverse transcriptase K103N/Y181C double mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 496.64, ALogP 6.11, HBA 8, HBD 1, PSA 86.96, QED 0.31
Compound (SMILES): CCC(=O)NCCNC(=O)CCc1cn(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)cn1
InChIKey: SADFFAQSWHTWLL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from human muscarinic M1 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 627.79, ALogP 4.27, HBA 7, HBD 3, PSA 128.67, QED 0.23
Compound (SMILES): O=C1SCCc2nc(-c3ccc(C(F)(F)F)cc3)[nH]c(=O)c21
InChIKey: YAAIOGGCMLWOPM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of recombinant human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 cells measured after 1 hr by chemiluminescence assay
Measurement: IC50 = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 326.3, ALogP 2.89, HBA 4, HBD 1, PSA 62.82, QED 0.88