lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(Cl)cc1Cl
InChIKey: SNYZZKKVKCUZEG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 348.19, ALogP 4.15, HBA 4, HBD 1, PSA 68.01, QED 0.77
Compound (SMILES): CC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(S(=O)(=O)C(C)C)cn23)CC1
InChIKey: IGYBKFSRFDAESW-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 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 475.01, ALogP 3.5, HBA 6, HBD 0, PSA 74.99, QED 0.57
Compound (SMILES): CCN(CC)CCNC(=O)c1cc(C(CC)(CC)c2ccc(OCS(=O)(=O)c3ccccc3)c(C)c2)cn1CC
InChIKey: WQAGUZXTQVTIRL-UHFFFAOYSA-N
Target: Vitamin D3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P11473
Assay: Binding affinity to VDR in scrambled siRNA-transfected human MCF7 cells assessed as cell growth inhibition by measuring reduction in BrdU incorporation after 16 hrs by ELISA
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 567.8, ALogP 5.8, HBA 6, HBD 1, PSA 80.64, QED 0.25
Compound (SMILES): CC(C)(c1ccc(Cl)cc1)c1cc(O)n(-c2cc(C(=O)O)ccn2)n1
InChIKey: KZVFIAJADGKVPK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 357.8, ALogP 3.65, HBA 5, HBD 2, PSA 88.24, QED 0.74
Compound (SMILES): CNC(=O)c1cccc(-c2c(-c3cc(C(=O)O)ccn3)ncn2C)c1
InChIKey: IOCMNXRIFNSUHI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 336.35, ALogP 2.21, HBA 5, HBD 2, PSA 97.11, QED 0.76
Compound (SMILES): CC(C)(O)CC(=O)NCCc1ccc2ncnc(Nc3ccc(Oc4cccc(C(F)(F)F)c4)c(Cl)c3)c2c1
InChIKey: PDXFYKHCQHPMFZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/L858R mutant (unknown origin)
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 558.99, ALogP 6.66, HBA 6, HBD 3, PSA 96.37, QED 0.21
Compound (SMILES): Clc1ccc(-c2c(-c3cc(-c4nn[nH]n4)ccn3)ncn2CC2CC2)cc1
InChIKey: SVBPSIGYLVRIFY-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 377.84, ALogP 3.86, HBA 6, HBD 1, PSA 85.17, QED 0.57
Compound (SMILES): Fc1ccc2c(C3CCN(CCN4CCCCC4)CC3)noc2c1
InChIKey: MKLRZKCKJQKVTL-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 331.43, ALogP 3.63, HBA 4, HBD 0, PSA 32.51, QED 0.86
Compound (SMILES): Nc1oc2cnccc2c1Nc1ccc(F)cc1Br
InChIKey: BXZRVBGOJMOAMS-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 322.14, ALogP 4.06, HBA 4, HBD 2, PSA 64.08, QED 0.75
Compound (SMILES): Cc1cc(NC(=O)Nc2cc(S(N)(=O)=O)cc([N+](=O)[O-])c2O)ccc1F
InChIKey: NCXBXYIRLDJNEP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of carbonic anhydrase 9 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 384.35, ALogP 2.04, HBA 6, HBD 4, PSA 164.66, QED 0.36
Compound (SMILES): Clc1ccc2c(n1)O[C@]13CC[C@H]1NC[C@H]23
InChIKey: CRXFCGUGNWJSEY-XLDPMVHQSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Displacement of [3H]epibatidine from alpha7 nAChR (unknown origin) expressed in HEK cell membranes after 4 hrs by liquid scintillation counting method
Measurement: Ki = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 222.67, ALogP 1.72, HBA 3, HBD 1, PSA 34.15, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(=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: QVBLFUZCOMZKBR-FRBREJNYSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 4064.54
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCCCc3cn(CCOCCOc4ccc(-c5cc(=O)c6cc(F)ccc6o5)cc4)nn3)ccc12
InChIKey: ACTUKRWKENIPCH-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 172.3 nM (pChEMBL 6.760000228881836)
Descriptors: MW 687.72, ALogP 7.46, HBA 10, HBD 0, PSA 118.82, QED 0.1
Compound (SMILES): Cn1c(=O)c2cc(S(=O)(=O)NC3(C)CC3)ccc2n(CC2CC2)c1=O
InChIKey: AXMXMMJXTSJFHK-UHFFFAOYSA-N
Target: ADP-ribosylhydrolase ARH3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NX46
Assay: Inhibition of human full length C-terminus His-tagged ARH3 expressed in Escherichia coli using Bt-NAD ribosylated PARP1 substrate after 30 mins by TR-FRET assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 363.44, ALogP 0.94, HBA 6, HBD 1, PSA 90.17, QED 0.86
Compound (SMILES): NC(=O)c1cc(F)cc2[nH]c(-c3cc4c(s3)CNCC4)nc12
InChIKey: DAIMOGAYMHVUBZ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Binding affinity to PARP1 (unknown origin) by ITC
Measurement: Kd = 20.3 nM (pChEMBL 7.690000057220459)
Descriptors: MW 316.36, ALogP 2.18, HBA 4, HBD 3, PSA 83.8, QED 0.68
Compound (SMILES): Nc1oc2cnc(Cl)cc2c1Nc1ccc(F)c(Cl)c1
InChIKey: XRKNWZFHCOFEGR-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 312.13, ALogP 4.6, HBA 4, HBD 2, PSA 64.08, QED 0.68
Compound (SMILES): Cc1nn(C(=O)c2cccnc2)c(N)c1-c1ccc(Cl)c(Cl)c1
InChIKey: AXKOZAJLACUUNC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged NIK (M1 to P947 residues) expressed in Sf9 insect cells using AKDVDQGSLCTSFVGTLQY peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 347.21, ALogP 3.83, HBA 5, HBD 1, PSA 73.8, QED 0.76
Compound (SMILES): COc1cc(C(=O)NS(=O)(=O)c2cccc(Cl)c2)ccc1Cc1cn(C)c2ccc(NC(=O)NC3CCCCC3)cc12
InChIKey: NUUXRXDZKMLTMN-UHFFFAOYSA-N
Target: Cysteinyl leukotriene receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y271
Assay: Antagonist potency at human CysLT1R expressed in African green monkey COS7 cells assessed as inhibition of LTD4-induced Ca2+ levels after 60 mins by fura-2/AM-fluorescence based spectrofluorimetry
Measurement: Kd = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 609.15, ALogP 6, HBA 6, HBD 3, PSA 118.53, QED 0.23
Compound (SMILES): Cn1cc(-c2ccc(C(F)(F)F)cc2)c2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc21
InChIKey: QUKXWNWVUDCALS-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin) expressed in HEK293 cells at -40 mV holding potential measured after 600 secs by patch clamp method
Measurement: IC50 = 3818 nM (pChEMBL 5.420000076293945)
Descriptors: MW 440.42, ALogP 4.23, HBA 4, HBD 1, PSA 68.17, QED 0.62
Compound (SMILES): FC1(F)CC(Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3cncc(C(F)(F)F)n3)n2)C1
InChIKey: QQGZDIVDOFXSIU-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 492.33, ALogP 4.71, HBA 8, HBD 2, PSA 101.4, QED 0.49
Compound (SMILES): Cc1ncc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3CC3)c2=O)s1
InChIKey: VHRYOZHNFLYWFP-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: Inhibition of human full length PARG using Bt-NAD ribosylated PARP1 substrate after 10 mins by TR-FRET assay
Measurement: EC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 460.58, ALogP 2.22, HBA 8, HBD 1, PSA 103.06, QED 0.58
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@@H]1CN(C(=O)CC#N)CC12CC2
InChIKey: VCBQNQKWRAHHIR-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro JAK Kinase Inhibition Test: Kinases used were human-derived JAK1, JAK2, JAK3, and TYK2 (Millipore, Germany). Each of these kinases was diluted with a suitable buffer solution as described below, and then mixed with reagents. Kinase-activity inhibitory effects of some of the compounds of Examples 1 to 73 (for example, Examples 5, 55, and 66) for JAK1, JAK2, JAK3, and TYK2 were measured at various concentrations by the above-described method, and IC50 values were determined. The IC50 values of the test compounds were calculated from % inhibition values of the compounds, by the Cheng-Prusoff method (Biochem. Pharmacol. (1973) 22, 3099-3108).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 310.36, ALogP 1.3, HBA 5, HBD 1, PSA 88.91, QED 0.92
Compound (SMILES): CCCc1nccc2c(Nc3cccc(C(F)(F)F)c3)c(N)oc12
InChIKey: RCJAABLMTMQMKO-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 335.33, ALogP 5.12, HBA 4, HBD 2, PSA 64.08, QED 0.69
Compound (SMILES): C[C@H](NC(=O)c1ccc(OCc2ccccc2)cc1)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCc1ccccc1
InChIKey: MVIKIWUDHUBUEP-LJWWSQQRSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta-5 using Suc-LLVY-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 606.68, ALogP 3.42, HBA 6, HBD 5, PSA 145.86, QED 0.17
Compound (SMILES): COc1ccc(-c2ccc(OCC(=O)NCCCN3CCCCC3)cc2)cc1
InChIKey: ZRDFCDGVKGMYOD-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Anopheles gambiae
UniProt: Q869C3
Assay: Inhibition of recombinant Anopheles gambiae AChE1 G122S mutant expressed in sf9 insect cells using acetylthiocholine iodide as substrate measured over 60 secs by Ellman assay
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 382.5, ALogP 3.73, HBA 4, HBD 1, PSA 50.8, QED 0.67
Compound (SMILES): FC1(F)CC(CNc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: OWAVUCAENWNGFB-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 505.37, ALogP 5.57, HBA 7, HBD 2, PSA 88.51, QED 0.42
Compound (SMILES): CCOC(=O)CNC(=O)N1CCN(c2ccc(/C=C/c3cc(Cl)cc(Cn4ccnc4)c3)cc2)CC1
InChIKey: YVJWIKSYYQKLFE-ONEGZZNKSA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of recombinant CYP21 (unknown origin) expressed in human AD293 cells using 17alpha-hydroxyprogesterone as substrate pretreated for 60 mins followed by substrate addition and measured after 45 mins by LC/MS analysis
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 508.02, ALogP 4.15, HBA 6, HBD 1, PSA 79.7, QED 0.37
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCCCc3cn(CCOCCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)nn3)ccc12
InChIKey: DLQHBQVMDBQBMU-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 669.73, ALogP 7.32, HBA 10, HBD 0, PSA 118.82, QED 0.1
Compound (SMILES): C[C@@H](Nc1nc(Nc2ccnc(-c3ccc(C#N)cc3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: AJWRMQNOMTURBI-CYBMUJFWSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 530.44, ALogP 5.99, HBA 8, HBD 2, PSA 112.3, QED 0.29
Compound (SMILES): CCCCNc1ncc2c(-c3ccc(NC4CCNCC4)cc3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: ZFBBKOBKYNRTOS-YHBQERECSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) using 5'-FAM-KKKKEEIYFFF-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 462.64, ALogP 4.95, HBA 7, HBD 4, PSA 87.03, QED 0.35
Compound (SMILES): Cc1cc(-c2nc(C)cc3c(Nc4ccc(F)c(Cl)c4)c(N)oc23)ccn1
InChIKey: GXCFTAUODPWTNA-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 382.83, ALogP 5.62, HBA 5, HBD 2, PSA 76.97, QED 0.48
Compound (SMILES): CCCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCCCN(CC)CC)cc2)n(CCCC)c1=O
InChIKey: FCICSYWLKUXKAR-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-602 from human adenosine A2B receptor expressed in CHO cell membranes
Measurement: Ki = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 609.82, ALogP 3.64, HBA 10, HBD 1, PSA 106.63, QED 0.22
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)[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: JWGNHMIXIYYMOO-GONAQTSYSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 4064.54
Compound (SMILES): CC(Cc1ccccc1)n1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: IHONAIAVRWABIE-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 uM 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 uM sodium L-ascorbate, 5 uM ammonium iron(II) sulfate. Reaction product is 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 ug/ml beads.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 330.4, ALogP 3.53, HBA 5, HBD 1, PSA 72.28, QED 0.61
Compound (SMILES): c1ccc2c(Cn3cnc(-c4cc(-c5nn[nH]n5)ccn4)c3)cccc2c1
InChIKey: RWLJOLCFWMAJGE-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 353.39, ALogP 3.33, HBA 6, HBD 1, PSA 85.17, QED 0.54
Compound (SMILES): CCC(CC)[C@H](NC(C)=O)[C@@H]1[C@H](OC(=O)NCCCOC(=O)/C=C/c2ccc(O)c(O)c2)[C@@H](C(=O)O)C[C@H]1NC(=N)N
InChIKey: DOIYAGBAFZCYFH-KWKBSNTCSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus (A/WSN/1933(H1N1)) recombinant neuraminidase H275Y mutant expressed in HEK293 cells pre-incubated for 10 mins before 4-MUNANA substrate addition by fluorometry
Measurement: IC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 591.66, ALogP 1.65, HBA 9, HBD 8, PSA 233.39, QED 0.04
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(Cl)c(OCc3ccc(F)cc3)c2)c1
InChIKey: YALQAUZSXADMLL-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 453.86, ALogP 4.92, HBA 6, HBD 1, PSA 86.47, QED 0.41
Compound (SMILES): CC(=O)NCC(=O)N1[C@@H]2CC[C@H]1c1ccc(Nc3ncc(C(F)(F)F)c(NC4CCC4)n3)cc12
InChIKey: RYYNGWLOYLRZLK-RBUKOAKNSA-N
Target: Acyl-CoA dehydrogenase family member 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6JQN1
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 474.49, ALogP 4.06, HBA 6, HBD 3, PSA 99.25, QED 0.58
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](CCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: RURUHDYEMBKXIP-DVIQCWQXSA-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 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 4036.49
Compound (SMILES): O=C(O)C1CCCN(C/C=C/C(c2ccc3c(c2)OCO3)(c2ccc3c(c2)OCO3)c2ccc3c(c2)OCO3)C1
InChIKey: WEIMTPANZVJKSW-WTDSWWLTSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 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 = 24547.09 nM (pChEMBL 4.610000133514404)
Descriptors: MW 543.57, ALogP 4.56, HBA 8, HBD 1, PSA 95.92, QED 0.34
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCC3CCCCC3)cn2)c1
InChIKey: JJIYEQBZHWJIEX-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 299.37, ALogP 3.61, HBA 4, HBD 1, PSA 68.01, QED 0.92
Compound (SMILES): Cc1nc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)c[nH]1
InChIKey: LRORKNAAPJYJSX-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 371.34, ALogP 2.99, HBA 6, HBD 3, PSA 91.41, QED 0.7
Compound (SMILES): CC(C)C(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1
InChIKey: RNHDGJROFDMRJA-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 345.41, ALogP 3.37, HBA 6, HBD 1, PSA 85.17, QED 0.6
Compound (SMILES): O=C(COc1ccc(I)cc1)NCCCN1CCCCC1
InChIKey: DOMQEJAUBXIDNR-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 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 402.28, ALogP 2.66, HBA 3, HBD 1, PSA 41.57, QED 0.56
Compound (SMILES): CN(C)CCCOc1cccc(/C=C2\COc3ccccc3C2=O)c1
InChIKey: DKAZPBKVFIJMAG-GHRIWEEISA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 93700 nM (pChEMBL 4.03000020980835)
Descriptors: MW 337.42, ALogP 3.68, HBA 4, HBD 0, PSA 38.77, QED 0.6
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(CNC(N)=S)CC3
InChIKey: HWMXBPNNULQCOI-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 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 286.4, ALogP 2.71, HBA 2, HBD 2, PSA 47.28, QED 0.85
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCNCc3ccccc3Cl)cn2)c1
InChIKey: HXFAEJNSXYWOET-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 356.81, ALogP 3.09, HBA 5, HBD 2, PSA 80.04, QED 0.64
Compound (SMILES): Fc1c(Cn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)cccc1OC(F)(F)F
InChIKey: NZTCCZUHIHSENS-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, 5 μM ammonium iron(II) sulfate. Reaction product is 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 are 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 is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul 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 will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 404.33, ALogP 3.82, HBA 6, HBD 1, PSA 81.51, QED 0.51
Compound (SMILES): Cc1nc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)c[nH]1
InChIKey: OMGWTZOTCFNMGJ-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 427.45, ALogP 4.55, HBA 6, HBD 3, PSA 91.41, QED 0.61
Compound (SMILES): N#Cc1cc(Nc2cc(NC3CC3)c3ncc(C(N)=O)n3n2)cc(C(F)(F)F)c1
InChIKey: LZDFDVIPCRRLMW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 JH2 domain (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 401.35, ALogP 3.04, HBA 7, HBD 3, PSA 121.13, QED 0.6
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCCc4ccccc43)cn2)c1
InChIKey: XSSUXYYELFOOBB-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 348.41, ALogP 3.1, HBA 5, HBD 1, PSA 71.25, QED 0.77
Compound (SMILES): C[C@@H](Nc1nc(NC(=O)c2ccccc2)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: IQRLKQDCDTZTJN-GFCCVEGCSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.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-R132 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); 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 90 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: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 428.42, ALogP 4.42, HBA 6, HBD 2, PSA 92.69, QED 0.6
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(F)c(F)c2)c1
InChIKey: GMWKOCOYZWNSIJ-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): COc1ccc(C(/C=C/CN2CCC[C@H](C(=O)O)C2)(c2ccc(OC)cc2)c2ccc3sccc3c2)cc1
InChIKey: BCLUMDBGGSYAHR-UZJKPBDZSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 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 = 2818.38 nM (pChEMBL 5.550000190734863)
Descriptors: MW 527.69, ALogP 6.61, HBA 5, HBD 1, PSA 59, QED 0.2
Compound (SMILES): FC(F)(F)c1[nH]nnc1-c1ccnc(-c2cn(CC3CCc4ccccc43)cn2)c1
InChIKey: JAGKRJVLUACVQE-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 uM 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 uM sodium L-ascorbate, 5 uM ammonium iron(II) sulfate. Reaction product is 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 ug/ml beads.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 410.4, ALogP 4.48, HBA 5, HBD 1, PSA 72.28, QED 0.54
Compound (SMILES): NS(=O)(=O)c1ccc(O)c(NC(=O)Nc2ccc(Oc3ccccc3)cc2)c1
InChIKey: WHGMLVAKKTTWJR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 399.43, ALogP 3.48, HBA 5, HBD 4, PSA 130.75, QED 0.49
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H]3C(=O)N(CC)C(=O)N23)o1
InChIKey: VKKJMPZSQBNIOL-VQIMIIECSA-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 363.42, ALogP 3.62, HBA 3, HBD 1, PSA 69.55, QED 0.72
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(-c3ccnc(N4CCNCC4)c3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: BTHRAPVJUCSEGQ-JBACZVJFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) using 5'-FAM-KKKKEEIYFFF-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 463.63, ALogP 3.98, HBA 8, HBD 3, PSA 91.13, QED 0.49
Compound (SMILES): CCn1cc(C2CCN(C(=O)C3CCCC3)CC2)c2cc(NC(=O)c3cc(C#N)ccn3)ccc21
InChIKey: HGQGBGOXODGAQZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human N-terminal 6His-tagged-RORC2 LBD (259 to 483 residues) expressed in Escherichia coli (DE3) cells assessed as inhibition of biotinylated co-activator SRC1-2 peptide recruitment after 3 hrs by TR-FRET assay
Measurement: IC50 = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 469.59, ALogP 5.08, HBA 5, HBD 1, PSA 91.02, QED 0.56
Compound (SMILES): FC1(F)CC(Nc2nc(NC3CC(F)(F)C3)nc(-c3cncc(C(F)(F)F)n3)n2)C1
InChIKey: BJUUMSAHTGGBTK-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 437.32, ALogP 3.77, HBA 7, HBD 2, PSA 88.51, QED 0.69
Compound (SMILES): O=C(O)c1ccc(N2CC3(CCN(Cc4cc(C(F)(F)F)ccc4C4CC4)CC3)OC2=O)cc1
InChIKey: UNCDRASKFWAOIZ-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 474.48, ALogP 5.27, HBA 4, HBD 1, PSA 70.08, QED 0.64