lovingscience/chembl-v37-raw-activities huggingface dataset:
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)CC(=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[C@@H](CCC(N)=O)C(=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: LKSFRQTUWHNAHW-QVJUSLJMSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 4064.54
Compound (SMILES): CC(C)CCC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(=O)O)=C[C@@H]1NC(=N)N
InChIKey: CGSNXPGJUHSVOX-ZZEHVWSGSA-N
Target: Sialidase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y3R4
Assay: Competitive inhibition of N-terminal MBP-fused human NEU2 expressed in Escherichia coli using 4MU-NANA as substrate preincubated with substrate for 15 mins and measured every min for 30 mins by Lineweaver-Burk plot analysis
Measurement: Ki = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 388.42, ALogP -2.16, HBA 7, HBD 8, PSA 198.22, QED 0.16
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CC3CCCCC3)cn2)c1
InChIKey: QUFQGCNSUGFPRL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 285.35, ALogP 3.22, HBA 4, HBD 1, PSA 68.01, QED 0.94
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[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: RHEAEZCLHHMNBA-GONAQTSYSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 4064.54
Compound (SMILES): COCC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3Cl)nc3ccc(N(C)S(C)(=O)=O)cn23)CC1
InChIKey: SWQAUJMELRFWKI-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 540.47, ALogP 2.99, HBA 7, HBD 0, PSA 87.46, QED 0.46
Compound (SMILES): CC(F)(F)c1cccc(-c2nc(Nc3ccnc(C4(C#N)CC4)c3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: RTZBPKFZOQGNAS-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 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 484.46, ALogP 4.95, HBA 8, HBD 2, PSA 112.3, QED 0.45
Compound (SMILES): COc1ccc(C(C/C=C/CN2CCCC(C(=O)O)C2)(c2ccc(OC)cc2)c2ccc(OC)cc2)cc1
InChIKey: YZTTZGKNHRIXLQ-SNAWJCMRSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by liquid scintillation counting method
Measurement: IC50 = 41686.94 nM (pChEMBL 4.380000114440918)
Descriptors: MW 515.65, ALogP 5.79, HBA 5, HBD 1, PSA 68.23, QED 0.26
Compound (SMILES): CC(Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1)c1cccc(F)c1
InChIKey: JYVZJECTMOHVFX-PZORYLMUSA-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 446.45, ALogP 5.48, HBA 6, HBD 2, PSA 75.62, QED 0.47
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCCCc4cn(CCOCCOc5ccc(-c6cc(=O)c7ccccc7o6)cc5)nn4)cc3)cc(=O)c2c1
InChIKey: GLTDJGDMOBNAFU-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 683.76, ALogP 7.63, HBA 10, HBD 0, PSA 118.82, QED 0.1
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)cc1)c1cc(Br)cc(Br)c1O
InChIKey: IUQCCIKCYKEUBD-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coli DH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured MDH refolding after 20 to 40 mins by spectrometric analysis
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 536.27, ALogP 6.93, HBA 5, HBD 2, PSA 62.22, QED 0.3
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3)c(CN3CCOCC3)n2c1)S(C)(=O)=O
InChIKey: JONTZUKTDXOBKU-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 434.95, ALogP 2.88, HBA 6, HBD 0, PSA 67.15, QED 0.62
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)C3)nc(-c3nc(C(F)(F)F)cs3)n2)C1
InChIKey: CAFOCHZZWAYFKC-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 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 470.42, ALogP 5.21, HBA 7, HBD 2, PSA 75.62, QED 0.58
Compound (SMILES): Cc1cc(F)ccc1Cc1cc(O)n(-c2cc(C(=O)O)ccn2)n1
InChIKey: IMBKDDQOCYXZQH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Activity 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 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 327.31, ALogP 2.71, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): COCc1cc(O)n(-c2cc(C(=O)O)ccn2)n1
InChIKey: XRHOGEKRJFLZGA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in Escherichia coli using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 249.23, ALogP 0.82, HBA 6, HBD 2, PSA 97.47, QED 0.83
Compound (SMILES): CC(CC#N)Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: IFMDZJNJPFFCSK-RRKGBCIJSA-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 391.4, ALogP 3.88, HBA 7, HBD 2, PSA 99.41, QED 0.74
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(S(N)(=O)=O)cc3)CC2)nc2cc[nH]c12
InChIKey: XVUDRALPLQPOCV-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase K103N mutant infected in human MT4 cells assessed as protection against virus-induced cytotoxicity by MTT assay
Measurement: EC50 = 1.03 nM (pChEMBL 8.989999771118164)
Descriptors: MW 531.64, ALogP 3.96, HBA 8, HBD 3, PSA 150.02, QED 0.32
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C/c2ccc(N3CCN(c4ccc(C(F)(F)F)cc4)CC3)cc2)cc1
InChIKey: YKENFXNYSIJFFJ-STBIYBPSSA-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 = 1931.7 nM (pChEMBL 5.710000038146973)
Descriptors: MW 503.55, ALogP 4.13, HBA 6, HBD 2, PSA 91.03, QED 0.39
Compound (SMILES): CC(F)(F)c1nc(-c2nc(NC3CCC(F)(F)C3)nc(NC3CCC(F)(F)C3)n2)cs1
InChIKey: OMZLJEXLAIMEOS-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 466.46, ALogP 5.31, HBA 7, HBD 2, PSA 75.62, QED 0.56
Compound (SMILES): COc1ccc(-n2c(C(=O)c3sc(Nc4ccc(Cl)cc4)nc3C)cnc2N)cc1
InChIKey: ZYWQJFQQSFZPIL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at recombinant human A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 439.93, ALogP 4.86, HBA 8, HBD 2, PSA 95.06, QED 0.42
Compound (SMILES): O=C(O)c1ccnc(-c2ncn(CC3CC3)c2-c2ccc(Cl)cc2)c1
InChIKey: QZSXNGRUEXSCKN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 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 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 353.81, ALogP 4.37, HBA 4, HBD 1, PSA 68.01, QED 0.74
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]1CCc2c(F)cccc21
InChIKey: HZUXFPDGVMNOOO-ZFIFVKQDSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 86.8 nM (pChEMBL 7.059999942779541)
Descriptors: MW 525.58, ALogP 2.16, HBA 6, HBD 3, PSA 133.68, QED 0.34
Compound (SMILES): CC(Nc1nc(NC(C)C(F)(F)F)nc(-n2ccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: FYQXPMJBVPBLMP-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 7.301000118255615)
Descriptors: MW 437.27, ALogP 3.8, HBA 7, HBD 2, PSA 80.55, QED 0.69
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1ccc(S(=O)(=O)F)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: HFSDFPGWRRLCFG-ZMVGRULKSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of biotinylated AVPF from N-terminal His tagged recombinant human XIAP-BIR3 Lys311Thr mutant expressed in Escherichia coli BL21(DE3) cells incubated for 2 hrs by DELFIA
Measurement: IC50 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 618.69, ALogP -0.63, HBA 8, HBD 5, PSA 196.87, QED 0.18
Compound (SMILES): CCC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(=O)O)=C[C@@H]1O
InChIKey: QOEZQHJNDYABPZ-FAMUSVHTSA-N
Target: Sialidase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WWR8
Assay: Inhibition of MBP-fused human NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 87000 nM (pChEMBL 4.059999942779541)
Descriptors: MW 305.28, ALogP -2.68, HBA 7, HBD 6, PSA 156.55, QED 0.31
Compound (SMILES): Cn1cc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)c(C(F)(F)F)n1
InChIKey: MZFAUIFIADPAFR-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C) Inhibitors: A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132H homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol) containing 5 μM NADPH and 37.5 μM NADP; 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 60 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: IDH1-R132C homodimer enzyme is diluted to 0.1875 μg/ml in 40 μl of Assay Buffer (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA) containing 5 uM NADPH and 28.75 uM NADP. The concentration of alpha-ketoglutarate in the Substrate Buffer is 1 mM.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 495.45, ALogP 5.27, HBA 7, HBD 2, PSA 80.55, QED 0.55
Compound (SMILES): CC(C)(C)c1cccc(OCCOc2ccc3c(c2)OCC3CC(=O)O)c1
InChIKey: DPLUHNJIYWLIIS-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human GAL4 fused PPARalpha-LBD expressed in human HepG2 cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 370.45, ALogP 4.39, HBA 4, HBD 1, PSA 64.99, QED 0.73
Compound (SMILES): COc1ccccc1-c1nccc2c(Nc3ccc(F)c(F)c3)c(N)oc12
InChIKey: IWYFYHUBDOWESR-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: In-vitro IDO1 Enzyme (Indoleamine 2,3-dioxygenase) Assay: Human indoleamine 2,3-dioxygenasel (hIDO1) catalyzes the oxidative cleavage of the pyrrole ring of the indole nucleus of tryptophan to yield N-formylkynurenine which can be converted to kynurenine (KYN) by deformylation. hIDO1 with an N-terminal His tag, expressed and purified from E. coli cells was procured from either Enzo LifeScienccs, NY, USA). Unless otherwise stated, all materials were procured from Sigma Aldrich, Mo., USA.The assay monitoring the conversion of L-tryptophan to KYN was carried out as follows. hIDO1 (10 nM) was incubated with tryptophan (30 μM) in the presence of ascorbic acid (20 mM), methylene blue (10 μM) and catalase (100 μg/mL) in potassium phosphate buffer (50 mM; pH 6.5) at 37C for 30 min. The reaction was terminated with 30% trichloroacetic acid (TCA) and further incubated at 65C for 15 min to fully convert N-formylkynurenine to KYN. The reaction mixture was then centrifuged to remove sediments and the KYN in the supernatant was estimated by UV-visible absorption spectroscopy at 360 nm using a Waters HPLC system fitted with a C-18 column or by LC/MS/MS. See, Sono, 1980, J. Biol. Chem., 255:1339-1345, which is herein incorporated by reference.Percent inhibition at each concentration of test compounds was determined by estimating the decrease in KYN with reference to the reaction control with 1% DMSO vehicle. Data were analyzed using nonlinear regression to generate IC50 values using Graph Pad Prism 5.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 367.36, ALogP 5.11, HBA 5, HBD 2, PSA 73.31, QED 0.52
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCc3ccc(F)cc3)cn2)c1
InChIKey: MDBCUBGXHYXSNR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 311.32, ALogP 3.03, HBA 4, HBD 1, PSA 68.01, QED 0.79
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(F)cc2F)c1
InChIKey: QNCYOEYMNMZNBO-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 < 100 nM (pChEMBL 7)
Descriptors: MW 331.28, ALogP 2.82, HBA 5, HBD 1, PSA 77.24, QED 0.78
Compound (SMILES): CS(=O)(=O)Nc1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)c4ccnnc4)CC3)n2c1
InChIKey: ADVAZMVHCQUELK-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 560.47, ALogP 3.43, HBA 8, HBD 1, PSA 112.8, QED 0.38
Compound (SMILES): CC1=Nc2c(F)cc(-c3nc(Nc4ccc(C5CCN(C)CC5)cn4)ncc3F)cc2C12CCCC2
InChIKey: AEFFENQISAXIKE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 cytoplasmic domain (781 to 1124 residues) expressed in baculovirus expression system using ULight-JAK-1 peptide as substrate preincubated for 15 mins followed by ATP addition measured after 90 mins
Measurement: IC50 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 488.59, ALogP 6.29, HBA 6, HBD 1, PSA 66.3, QED 0.47
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)cc1)c1ccccc1O
InChIKey: WKBVMOQHKHAJNZ-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding after 40 to 60 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 378.48, ALogP 5.41, HBA 5, HBD 2, PSA 62.22, QED 0.5
Compound (SMILES): O=c1cc(Sc2cccc(-c3ccc(Cl)cc3)c2)[nH]c(=O)n1O
InChIKey: JWNGNXCNIMNVGU-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 346.8, ALogP 3.25, HBA 5, HBD 2, PSA 75.09, QED 0.56
Compound (SMILES): COc1nc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: KVGQFDSHCXICPE-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of human N-terminal GST-tagged ROS cytoplasmic domain (1883 to 2347 residues) expressed in baculovirus expression system after 1 hr by mobility shift assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 519.03, ALogP 3.14, HBA 10, HBD 3, PSA 124.61, QED 0.41
Compound (SMILES): CCCCCCC(CCCC(=O)Nc1ccccc1)CCC(=O)NO
InChIKey: UXLCJJCZCBKZAI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa-S3 cell lysates preincubated for 15 mins followed by HDAC-Glo substrate addition measured after 30 to 40 mins by fluorimetric method
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 348.49, ALogP 4.67, HBA 3, HBD 3, PSA 78.43, QED 0.28
Compound (SMILES): CCOc1cc(Cl)ccc1-c1c(-c2cc(C(=O)O)ccn2)ncn1C
InChIKey: LPZRXVYRMUKTQA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 357.8, ALogP 3.9, HBA 5, HBD 1, PSA 77.24, QED 0.75
Compound (SMILES): Fc1ccc(Cn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: CJUOHMUQVUCXSI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: Inhibition of recombinant human C-terminal FLAG-tagged JMJD3 (1043 to end residues) expressed in baculovirus infected Sf9 cells using H3K27me3-biotin labelled peptide as substrate measured after 20 mins by AlphaScreen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 388.33, ALogP 3.94, HBA 5, HBD 1, PSA 72.28, QED 0.54
Compound (SMILES): CCCSc1nc(NC(C)=O)cc(OC(C)c2ccccc2)n1
InChIKey: JKHKXGWHVHXXCS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]NECA from recombinant human adenosine A2B receptor expressed in CHO cell membranes measured after 180 mins
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 331.44, ALogP 4.08, HBA 5, HBD 1, PSA 64.11, QED 0.61
Compound (SMILES): FC1(F)CC[C@@H](Nc2nc(N[C@H]3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: JWMKUJAOIPXYIG-PHIMTYICSA-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 7.301000118255615)
Descriptors: MW 464.39, ALogP 5.15, HBA 6, HBD 2, PSA 75.62, QED 0.6
Compound (SMILES): O=C(COc1ccc(-c2ccccc2)cc1)N1CCC(N2CCCCC2)CC1
InChIKey: NNJPSKCGFBHMTD-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE using acetylthiocholine iodide as substrate measured over 60 secs by Ellman assay
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 378.52, ALogP 4.21, HBA 3, HBD 0, PSA 32.78, QED 0.78
Compound (SMILES): CN(C/C=C/c1ccc(C(F)(F)F)cc1)Cc1ccc2c(c1)OCCO2.Cl
InChIKey: ALPVMHUDPXPFOA-SQQVDAMQSA-N
Target: 4,4'-diapophytoene desaturase (4,4'-diaponeurosporene-forming) (SINGLE PROTEIN), Staphylococcus aureus (strain Newman)
UniProt: O07855
Assay: Inhibition of CrtN in linezolid-resistant Staphylococcus aureus NRS271 assessed as reduction in staphyloxanthin levels after 48 hrs by spectrophotometric method-based pigment inhibition assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 363.38, ALogP 4.62, HBA 3, HBD 0, PSA 21.7, QED 0.77
Compound (SMILES): CCNC(=O)n1nc(C)c(-c2ccc(Cl)c(Cl)c2)c1N
InChIKey: FAIWIZRVRJFASV-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 313.19, ALogP 3.33, HBA 4, HBD 2, PSA 72.94, QED 0.89
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(N2CCCC2)cc1
InChIKey: RYHMPYHFLUZIAQ-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 < 100 nM (pChEMBL 7)
Descriptors: MW 348.41, ALogP 3.45, HBA 5, HBD 1, PSA 71.25, QED 0.78
Compound (SMILES): CCCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCc3ccc(Cl)cc3)cc2)n(CCCC)c1=O
InChIKey: LOBJSTKTEZNQLX-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine A3 receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 621.18, ALogP 4.76, HBA 9, HBD 1, PSA 103.39, QED 0.22
Compound (SMILES): Cc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H]3C(=O)N(C)CC(=O)N23)s1
InChIKey: LFVBPBWMEWDRAV-DNVCBOLYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of recombinant human N-terminal GST-tagged PDE3B (592 to end residues) expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 365.46, ALogP 2.85, HBA 3, HBD 1, PSA 56.41, QED 0.72
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)CO)CC3)n2c1)S(C)(=O)=O
InChIKey: JIEQXDSYOVDKRX-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 526.45, ALogP 2.34, HBA 7, HBD 1, PSA 98.46, QED 0.53
Compound (SMILES): CCOc1cc(CN2CCC(C3CCN(S(=O)(=O)c4ccccc4)CC3)CC2)cc(OCC)c1-c1ccc(F)cc1
InChIKey: LLMDFLGIOTWWTF-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse SSTR5 expressed in CHO-K1 cell membranes assessed as reduction in SST-28-induced inhibition of forskolin-stimulated cAMP accumulation by LANCE assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 580.77, ALogP 6.6, HBA 5, HBD 0, PSA 59.08, QED 0.27
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3)c(CN3CCN(C(=O)c4ccnnc4)CC3)n2c1)S(C)(=O)=O
InChIKey: QWBFJXSZSFCANR-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 540.05, ALogP 2.8, HBA 8, HBD 0, PSA 104.01, QED 0.37
Compound (SMILES): C[C@H](Nc1nc(Nc2ccnc(C3(C#N)CC3)c2)nc(-n2ccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: VXRYLBWUODLCCR-JTQLQIEISA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 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 483.38, ALogP 4.13, HBA 9, HBD 2, PSA 117.23, QED 0.5
Compound (SMILES): CC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1Cc2c[n+](cn2CCCCCCCCc2ccccc2)CCCCCCNC(=O)[C@H]([C@@H](C)OP(=O)(O)O)NC(=O)[C@H](CO)NC1=O
InChIKey: KPDOBADQSPMGFP-OELJMHDBSA-O
Target: Serine/threonine-protein kinase PLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H4B4
Assay: Inhibition of 5CF-PLATSpTPKNG-NH2 binding to Plk3 C-terminal polo-box domain (unknown origin) preincubated for 30 mins followed by probe addition measured after 30 mins by fluorescence polarization assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 946.12, ALogP 2.08, HBA 10, HBD 8, PSA 261.61, QED 0.06
Compound (SMILES): O=C(O)c1ccnc(-c2cn(C3Cc4ccccc4C3)cn2)c1
InChIKey: YEIUTPICFPHMSZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli 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 305.34, ALogP 2.98, HBA 4, HBD 1, PSA 68.01, QED 0.81
Compound (SMILES): CC(=O)Nc1ccc2c(OC(=O)[C@H]3[C@@H](c4ccccc4)[C@H](C(=O)O)[C@@H]3c3ccccc3)cccc2c1
InChIKey: BJJLYJAVBYSYDD-LJWNLINESA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: High Throughput Fluorescence Displacement Assay : FABP5 was purified and delipidated as described previously (Kaczocha, M. et al. 2012). FABP5 (30 μg), NBD-stearate (1 μM), and a competitor test compound were incubated in 30 mM Tris-HCl, 100 mM NaCl buffer (pH 7.6). Competitors included arachidonic acid, BMS309403, 48 test compounds from ChemDiv library, Compound 26 and Compound 49. The initial assay was run with buffer (30 mM Tris-HCl buffer), negative controls (buffer and NBD-stearate), positive controls (buffer, NBD-stearate, FABP5), and experimental wells with a variable test compound added (arachidonic acid or one of the 48 test compounds) at 10 μM. Test compounds that produced high inhibition and proved statistically significant were then added to the fluorescent assay at 10 μM and tested in triplicate to verify their success. The most effective test compound and BMS309403 were measured in increasing concentrations (0.01-50 μM), as were the Compound 26 and γ-truxillic acid 1-naphthyl ester, which were discovered following the test. The fluorescent assays were tested in the wells of Microtest 96-well Assay Plates, Optilux (BD Biosciences, Franklin Lakes, N.J.) and loss of fluorescence intensity was measured with a FLUOstar OPTIMA spectrofluorometer set to excitation and emission wavelengths of 460 nm and 544 nm, respectively. For the most effective test compounds, IC50 values were calculated with GraphPad Prism. GraphPad Prism was also used to determine the Ki of these select competitors from the equation Ki=IC50/(1+([NBD-stearate]/Kd)).
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 479.53, ALogP 5.6, HBA 4, HBD 2, PSA 92.7, QED 0.28
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(C)(CNC(C)=O)CC3
InChIKey: BCKYGUZOGCRTFP-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 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 283.37, ALogP 3.19, HBA 2, HBD 1, PSA 38.33, QED 0.94
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3ccc(C#N)cc3)CC2)cc(C(C)(C)C)c1O
InChIKey: UIDJKYIGMUKBSW-VAWYXSNFSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using p-tyramine as substrate incubated for 15 mins followed by substrate addition measured for 20 mins by fluorescence assay
Measurement: IC50 = 13900 nM (pChEMBL 4.860000133514404)
Descriptors: MW 501.72, ALogP 6.29, HBA 4, HBD 2, PSA 76.36, QED 0.44
Compound (SMILES): CC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(-c4ccccc4C#N)cn23)CC1
InChIKey: YGBQNJLVZNCOQE-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 469.98, ALogP 4.86, HBA 5, HBD 0, PSA 64.64, QED 0.43
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(=O)CCCCC)[C@H](O)C(C)C)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)OC)C(=O)O[C@H](C)[C@H](NC(C)=O)C(=O)O[C@H](Cc2ccccc2)C(=O)N1C
InChIKey: OIXFCGWUWTUMJO-BQFCSTJRSA-N
Target: Guanine nucleotide-binding protein subunit alpha-11 (SINGLE PROTEIN), Homo sapiens
UniProt: P29992
Assay: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 1016.2
Compound (SMILES): CCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCCc3ccc(S(N)(=O)=O)cc3)cc2)n(CCC)c1=O
InChIKey: WLWCSNFOHHXWJL-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine A3 receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 651.79, ALogP 2.02, HBA 11, HBD 2, PSA 163.55, QED 0.21
Compound (SMILES): CC(C)n1cc(CN2CCC3(CC2)CC(=O)N(c2ccc(C(=O)O)cc2)C3)c2c(C3CC3)cccc21
InChIKey: RXUODJMQFRVNSY-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 485.63, ALogP 5.82, HBA 4, HBD 1, PSA 65.78, QED 0.48
Compound (SMILES): CNc1ncc(C(=O)OCc2cccc(OC)c2)c2nc(-c3ccco3)nn12
InChIKey: VSVZDSXZJIFPKH-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 = 7.42 nM (pChEMBL 8.130000114440918)
Descriptors: MW 379.38, ALogP 2.79, HBA 9, HBD 1, PSA 103.78, QED 0.51
Compound (SMILES): Nc1sc2ccc(Cl)cc2c1Nc1ccccc1
InChIKey: NSMKMPYAQIAAQG-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: In-vitro IDO1 Enzyme (Indoleamine 2,3-dioxygenase) Assay: Human indoleamine 2,3-dioxygenasel (hIDO1) catalyzes the oxidative cleavage of the pyrrole ring of the indole nucleus of tryptophan to yield N-formylkynurenine which can be converted to kynurenine (KYN) by deformylation. hIDO1 with an N-terminal His tag, expressed and purified from E. coli cells was procured from either Enzo LifeScienccs, NY, USA). Unless otherwise stated, all materials were procured from Sigma Aldrich, Mo., USA.The assay monitoring the conversion of L-tryptophan to KYN was carried out as follows. hIDO1 (10 nM) was incubated with tryptophan (30 μM) in the presence of ascorbic acid (20 mM), methylene blue (10 μM) and catalase (100 μg/mL) in potassium phosphate buffer (50 mM; pH 6.5) at 37C for 30 min. The reaction was terminated with 30% trichloroacetic acid (TCA) and further incubated at 65C for 15 min to fully convert N-formylkynurenine to KYN. The reaction mixture was then centrifuged to remove sediments and the KYN in the supernatant was estimated by UV-visible absorption spectroscopy at 360 nm using a Waters HPLC system fitted with a C-18 column or by LC/MS/MS. See, Sono, 1980, J. Biol. Chem., 255:1339-1345, which is herein incorporated by reference.Percent inhibition at each concentration of test compounds was determined by estimating the decrease in KYN with reference to the reaction control with 1% DMSO vehicle. Data were analyzed using nonlinear regression to generate IC50 values using Graph Pad Prism 5.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 274.78, ALogP 4.88, HBA 3, HBD 2, PSA 38.05, QED 0.7
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)NC#N)ccn2)c1)CC1CC1
InChIKey: YLAZXWUGKKWCID-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 324.39, ALogP 1.5, HBA 6, HBD 1, PSA 86.84, QED 0.62
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCCc3cn(CCOCCOCCOc4ccc(-c5cc(=O)c6cc(F)ccc6o5)cc4)nn3)ccc12
InChIKey: QUCUORYCGHTGMM-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 328 nM (pChEMBL 6.480000019073486)
Descriptors: MW 717.75, ALogP 7.09, HBA 11, HBD 0, PSA 128.05, QED 0.09
Compound (SMILES): CNc1ncc(C(=O)OCc2ccc(OC)cc2)c2nc(-c3ccco3)nn12
InChIKey: AJNUBNSGQWWYDC-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 = 5.62 nM (pChEMBL 8.25)
Descriptors: MW 379.38, ALogP 2.79, HBA 9, HBD 1, PSA 103.78, QED 0.51
Compound (SMILES): C[C@@H](Nc1nc(NC2C3CC4CC(C3)CC2C4)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: IQUHQOIQGCZYCW-FGSOGITGSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C) Inhibitors: A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132H homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol) containing 5 μM NADPH and 37.5 μM NADP; 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 60 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: IDH1-R132C homodimer enzyme is diluted to 0.1875 μg/ml in 40 μl of Assay Buffer (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA) containing 5 uM NADPH and 28.75 uM NADP. The concentration of alpha-ketoglutarate in the Substrate Buffer is 1 mM.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 458.53, ALogP 5.4, HBA 6, HBD 2, PSA 75.62, QED 0.6
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: RAQUPWWEGSOPEV-UHFFFAOYSA-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 493.42, ALogP 5.7, HBA 7, HBD 2, PSA 99.41, QED 0.44