lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(Cl)n2)n1)C1CC1
InChIKey: GTMXNXATSGQGCH-GHMZBOCLSA-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 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 358.88, ALogP 4.01, HBA 6, HBD 2, PSA 75.62, QED 0.73
Compound (SMILES): CCN(CC)CCOc1cccc(/C=C2\COc3ccccc3C2=O)c1
InChIKey: BTMWXBQNIMYMKU-NBVRZTHBSA-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 = 80000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 351.45, ALogP 4.07, HBA 4, HBD 0, PSA 38.77, QED 0.71
Compound (SMILES): CC(C)(C#N)CNc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: LWUOICMGVABMMB-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 478.43, ALogP 5.16, HBA 8, HBD 2, PSA 112.3, QED 0.45
Compound (SMILES): O=C(Nc1ccnc(Cl)c1)Nc1cc(C(F)F)ns1
InChIKey: HJJABVPOIGJSFO-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51531
Assay: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 304.71, ALogP 3.77, HBA 4, HBD 2, PSA 66.91, QED 0.85
Compound (SMILES): CCCNC(=O)NCC1CCc2ccc3ccc(OC)nc3c21
InChIKey: DCMXVAZTUHQTTP-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 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 313.4, ALogP 2.98, HBA 3, HBD 2, PSA 63.25, QED 0.89
Compound (SMILES): Cc1cccc(Nc2c(N)oc3cc(C#N)ccc23)c1
InChIKey: LMGAXAXRFXNKFO-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 263.3, ALogP 3.94, HBA 4, HBD 2, PSA 74.98, QED 0.73
Compound (SMILES): OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCN(CCCCN(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: CVRMQFHSOSVJET-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from human 5-HT2B receptor expressed in HEK cells by radioligand binding assay
Measurement: Ki = 509 nM (pChEMBL 6.289999961853027)
Descriptors: MW 538.99, ALogP 7.54, HBA 3, HBD 1, PSA 26.71, QED 0.24
Compound (SMILES): Cc1ccccc1Cn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: IOKZWCBMXXDCIJ-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 384.37, ALogP 4.11, HBA 5, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): CCCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCCc3ccc(S(N)(=O)=O)cc3)cc2)n(CCCC)c1=O
InChIKey: VYOHUSOIZGQDAX-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 679.84, ALogP 2.8, HBA 11, HBD 2, PSA 163.55, QED 0.18
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(-c3ccc(Br)cc3)[se]2)cc1
InChIKey: RIVXATBATHBBHV-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of recombinant human carbonic anhydrase 5a incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 86.6 nM (pChEMBL 7.059999942779541)
Descriptors: MW 442.2
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3)c(CN3CCN(C(=O)C4COC4)CC3)n2c1)S(C)(=O)=O
InChIKey: VOTCYCXUADIEDK-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 518.04, ALogP 2.34, HBA 7, HBD 0, PSA 87.46, QED 0.5
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(C)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O
InChIKey: XVOPWUWRTVGXCT-ZXYZSCNASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-[Nle4,d-Phe7]-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 642.76, ALogP 1.55, HBA 6, HBD 7, PSA 203.96, QED 0.09
Compound (SMILES): COCC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(N(C)S(C)(=O)=O)cn23)CC1
InChIKey: DCAMMTAPONDXMO-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 506.03, ALogP 2.34, HBA 7, HBD 0, PSA 87.46, QED 0.49
Compound (SMILES): CCOC(=O)CN1C(=O)C(=NNC(=O)c2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: PFBMKJHLXRKXJY-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 430.44, ALogP 0.38, HBA 7, HBD 2, PSA 148.23, QED 0.5
Compound (SMILES): CC(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: HDWCWNNKLHTKJH-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 384.37, ALogP 4.36, HBA 5, HBD 1, PSA 72.28, QED 0.57
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(CNC(N)=O)CC3
InChIKey: AIOFAAQPUFNQBS-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 270.33, ALogP 2.55, HBA 2, HBD 2, PSA 64.35, QED 0.9
Compound (SMILES): CC[C@H](Nc1nc(N[C@@H](CC)C(F)(F)F)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: QTQWJQDDICMREO-UWVGGRQHSA-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 476.35, ALogP 5.46, HBA 6, HBD 2, PSA 75.62, QED 0.52
Compound (SMILES): COc1ccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: NSCFCNLNWUYORR-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 414.39, ALogP 4, HBA 6, HBD 1, PSA 81.51, QED 0.52
Compound (SMILES): Cc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)c(C#N)c1
InChIKey: VFQWDEDHEXEJLC-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 334.34, ALogP 2.72, HBA 6, HBD 1, PSA 101.03, QED 0.77
Compound (SMILES): CCOc1ccccc1NC(=O)Nc1cc(S(N)(=O)=O)ccc1O
InChIKey: BBIILYRHGSEGLE-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 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 351.38, ALogP 2.08, HBA 5, HBD 4, PSA 130.75, QED 0.61
Compound (SMILES): FC(F)c1csc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: GVVHKJZVVILBHY-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 424.37, ALogP 4.35, HBA 7, HBD 2, PSA 75.62, QED 0.67
Compound (SMILES): O=C1c2ccccc2C(=Cc2cccc(O)c2)c2ccccc21
InChIKey: KGQNBZACENOOOR-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P15207
Assay: Displacement of Fluormone-DHT from rat GST-tagged rat AR LBD expressed in insect cells after 4 hrs by fluorescence polarization assay
Measurement: IC50 = 625 nM (pChEMBL 6.199999809265137)
Descriptors: MW 298.34, ALogP 4.53, HBA 2, HBD 1, PSA 37.3, QED 0.56
Compound (SMILES): CNC(=O)c1cccc2cc(Oc3ccnc(NC(=O)c4ccc(N5CCN(CCO)CC5)cc4)c3)ccc12
InChIKey: AISWQGLURAAAKE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant FGFR3 (unknown origin) incubated for 60 mins by ELISA analysis
Measurement: IC50 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 525.61, ALogP 3.75, HBA 7, HBD 3, PSA 107.03, QED 0.32
Compound (SMILES): C[C@H]1Cc2ccc(-c3ncnc4[nH]ccc34)cc2[C@@H]1NC#N
InChIKey: FOOVWQSSBRMHTG-ZUZCIYMTSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 705 nM (pChEMBL 6.150000095367432)
Descriptors: MW 289.34, ALogP 2.93, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)cc1)c1cc(Br)cc(Br)c1
InChIKey: MWCTYQOZTHGGAI-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 520.27, ALogP 7.22, HBA 4, HBD 1, PSA 41.99, QED 0.31
Compound (SMILES): FC(F)(F)c1ccccc1CCn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: IQXPWKHDTIHLLB-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 rt for 40 min, 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 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 452.36, ALogP 5.01, HBA 5, HBD 1, PSA 72.28, QED 0.43
Compound (SMILES): OC[C@@H]1CCC[C@@H](c2ccc(O)cc2)CC1
InChIKey: TYZPZHWTUNATHL-VXGBXAGGSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Inhibition of fluorescein-tagged estrogen binding to GST-tagged ERalpha (unknown origin) ligand binding domain after 1 hr by LanthaScreen TR-FRET assay
Measurement: EC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 220.31, ALogP 3.05, HBA 2, HBD 2, PSA 40.46, QED 0.75
Compound (SMILES): CNc1ncc(C(=O)OCc2ccc(C)cc2)c2nc(-c3ccco3)nn12
InChIKey: LZDJWNMSPWMOSJ-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 = 3.72 nM (pChEMBL 8.430000305175781)
Descriptors: MW 363.38, ALogP 3.09, HBA 8, HBD 1, PSA 94.55, QED 0.54
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)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
InChIKey: ICCWQBANNIZSDH-ILMFCTMOSA-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 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 4213.78
Compound (SMILES): COc1cc(-c2nc(NCc3ccc(C(=O)NO)cc3)cc3c2[nH]c2ccccc23)cc(OC)c1OC
InChIKey: XVLFDROZMUKWLL-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 498.54, ALogP 5.14, HBA 7, HBD 4, PSA 117.73, QED 0.17
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cncc(Cl)n3)n2)CC1
InChIKey: MEWHAARPVJKYDP-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 459.88, ALogP 4.96, HBA 7, HBD 2, PSA 88.51, QED 0.61
Compound (SMILES): N#Cc1cc(Nc2nc(NC3CC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: RQRJJSVAJSUINU-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 448.36, ALogP 4.17, HBA 8, HBD 2, PSA 112.3, QED 0.56
Compound (SMILES): CCCCc1ccccc1NCc1ccc(C(=O)Nc2nc(CC(=O)O)cs2)s1
InChIKey: YSRCIJVCLXAWIY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 429.57, ALogP 5.04, HBA 6, HBD 3, PSA 91.32, QED 0.42
Compound (SMILES): CC(Nc1nc(NC(C)C(F)(F)F)nc(-c2cncc(Cl)n2)n1)C(F)(F)F
InChIKey: QETWKMKQNIKDLH-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 415.73, ALogP 3.71, HBA 7, HBD 2, PSA 88.51, QED 0.72
Compound (SMILES): O=S(=O)(Nc1ncns1)c1ccc(OCc2ccc(OC(F)(F)F)c(Cl)c2)cc1
InChIKey: XOYPCMZEMYSCQC-UHFFFAOYSA-N
Target: Sodium channel protein type 10 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y9
Assay: Inhibition of human NaV1.8
Measurement: IC50 = 15100 nM (pChEMBL 4.820000171661377)
Descriptors: MW 465.86, ALogP 4.47, HBA 7, HBD 1, PSA 90.41, QED 0.55
Compound (SMILES): O=C(O)c1ccnc(-n2nc(Cc3ccccc3)cc2O)c1
InChIKey: GAAWGDKZMZYRLG-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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 295.3, ALogP 2.26, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): N#CN[C@@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-CQSZACIVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 = 1118 nM (pChEMBL 5.949999809265137)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): CCOc1ccccc1CCn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: LAHJCVJYCGEQRW-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 rt for 40 min, 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 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 428.42, ALogP 4.39, HBA 6, HBD 1, PSA 81.51, QED 0.47
Compound (SMILES): Cn1cc(-c2ccc(C(F)F)cc2)c2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc21
InChIKey: ZDFIRHIJKVNVDY-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Mus musculus
UniProt: Q62205
Assay: Inhibition of recombinant mouse Nav1.7 expressed in HEK293 cells at -70 mV holding potential by patch clamp electrophysiology method
Measurement: IC50 = 231 nM (pChEMBL 6.639999866485596)
Descriptors: MW 422.43, ALogP 4.14, HBA 4, HBD 1, PSA 68.17, QED 0.67
Compound (SMILES): O=C(NCc1ccc(OC(F)(F)F)c(Cl)c1)c1ccc(S(=O)(=O)Nc2nccs2)c(F)c1
InChIKey: ZUXRUQOEFBOTGF-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human NaV1.6
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 509.89, ALogP 4.57, HBA 6, HBD 2, PSA 97.39, QED 0.45
Compound (SMILES): N#CC1(c2cc(Nc3nc(NCC(F)(F)F)nc(-c4cccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: BNHMYSZGOLVPEX-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 480.38, ALogP 4.62, HBA 8, HBD 2, PSA 112.3, QED 0.49
Compound (SMILES): CC(=O)n1nc(C)c(-c2ccc(Cl)c(Cl)c2)c1N
InChIKey: HJXDCOSNNVYHCY-UHFFFAOYSA-N
Target: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13131
Assay: Inhibition of AMPK alpha1 (unknown origin) (1 to 550 residues)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 284.15, ALogP 3.41, HBA 4, HBD 1, PSA 60.91, QED 0.87
Compound (SMILES): O=C(O)c1ccc2ccc(C(=O)c3ccc(C(F)(F)F)cc3)c-2cc1
InChIKey: AIHVJYFGVPIWAT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 344.29, ALogP 4.74, HBA 2, HBD 1, PSA 54.37, QED 0.7
Compound (SMILES): Nc1cccc(C(OCCN2CCCCC2)c2cc3nccc(C(=O)O)c3s2)c1
InChIKey: FTKYSFLMVOPKTH-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Irreversible inhibition of KDM5A ARID/PhD1 domain deletion mutant (1 to 739 residues) (unknown origin) using 1000 uM alpha-KG by succinate-glo demethylase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.53, ALogP 4.17, HBA 6, HBD 2, PSA 88.68, QED 0.57
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O
InChIKey: YIDIBSNLMUVHEC-YOGANYHLSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Activation of human Y1R expressed in HEK293 cells assessed as inhibition of isoproterenol-induced increase in intracellular cAMP levels by calcium 5 dye-based FLIPR assay
Measurement: EC50 > 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 4182.77
Compound (SMILES): CCC[C@@H](CCO)Nc1nc(N)nc2c1CN(C(=O)c1csc(C)n1)CC2
InChIKey: NGQVCINKVAWYDL-LBPRGKRZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 390.51, ALogP 1.99, HBA 8, HBD 3, PSA 117.26, QED 0.66
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(-c3ccc([N+](=O)[O-])cc3)[se]2)cc1
InChIKey: QKNVOKBWWPYBCJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human carbonic anhydrase 5b incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 757.3 nM (pChEMBL 6.119999885559082)
Descriptors: MW 408.3
Compound (SMILES): CCN(CC)CCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1
InChIKey: CZGKNDHIUAGCOG-OBGWFSINSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured at 1 to 3 mins time interval by Ellman's method
Measurement: IC50 = 3290 nM (pChEMBL 5.480000019073486)
Descriptors: MW 351.45, ALogP 4.07, HBA 4, HBD 0, PSA 38.77, QED 0.71
Compound (SMILES): O=C1[C@@H]2[C@H](C(=O)N1CCCCN1CCN(c3cccc4sccc34)CC1)[C@H]1C=C[C@@H]2C1
InChIKey: KVJXXDNXTCGJKY-BRNYJPRKSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Antagonist activity at histamine H1 receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 435.59, ALogP 3.61, HBA 5, HBD 0, PSA 43.86, QED 0.4
Compound (SMILES): CCOc1cc(CN2CC[C@H]3C(Nc4nc5ccc(C(=O)O)cc5o4)CC[C@H]32)cc(OCC)c1-c1ccc(F)cc1
InChIKey: VOZUDWOEAFDHSE-JNOFKKGSSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of MK-499 binding to human ERG
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 559.64, ALogP 6.59, HBA 7, HBD 2, PSA 97.06, QED 0.22
Compound (SMILES): CC(C)(O)CNc1nc(Nc2cc(F)cc(F)c2)nc(-c2nccc(C(F)(F)F)n2)n1
InChIKey: MDLNQVWWUAJKJT-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 441.36, ALogP 3.55, HBA 8, HBD 3, PSA 108.74, QED 0.5
Compound (SMILES): O=Cc1ccc2cccc(C(=O)Nc3ccc(C(F)(F)F)cn3)c2n1
InChIKey: RJUAKORAVOTBIE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of wild type non-phosphorylated N-terminal His6-tagged FGFR4 (G442 to E753 residues) (unknown origin) expressed in sf9 cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 as substrate after 60 mins by microfluidic mobility shift assay
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 345.28, ALogP 3.71, HBA 4, HBD 1, PSA 71.95, QED 0.73
Compound (SMILES): Clc1ccccc1Cn1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1
InChIKey: FQGUTBFYFQAJJX-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 337.77, ALogP 2.83, HBA 6, HBD 1, PSA 85.17, QED 0.62
Compound (SMILES): COc1ccc(S(=O)(=O)N[C@@H]2C[C@H](NC#N)c3cc(-c4ncnc5[nH]ccc45)ccc32)cc1
InChIKey: AEBJOZJYLXCLLU-LEWJYISDSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 in human PBMC assessed as reduction in IL15-induced STAT5 phosphorylation preincubated for 75 mins followed by IL15 addition and measured after 15 mins by FACS analysis
Measurement: IC50 = 947 nM (pChEMBL 6.019999980926514)
Descriptors: MW 460.52, ALogP 3.17, HBA 7, HBD 3, PSA 132.79, QED 0.3
Compound (SMILES): FC(F)c1cncc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: YIFYCTDCEXPZOP-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 419.33, ALogP 3.69, HBA 7, HBD 2, PSA 88.51, QED 0.69
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@H]3C(=O)N(CC)C(=O)N23)s1
InChIKey: PYRZRKTWNHDCON-QFBILLFUSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE4A1A expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 379.49, ALogP 4.09, HBA 3, HBD 1, PSA 56.41, QED 0.7
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H](C=O)O[C@@H](C=O)COP(=O)(O)OP(=O)(O)O
InChIKey: NVPIJHRHNNQNDN-NKWVEPMBSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22413
Assay: Noncompetitive-inhibition of recombinant human NPP1 expressed in HEK293 cell membranes using p-Nph-5'-TMP as substrate pretreated for 10 mins followed by substrate addition and measured after 60 mins by capillary electrophoresis method
Measurement: Ki = 3420 nM (pChEMBL 5.46999979019165)
Descriptors: MW 425.19, ALogP -1.08, HBA 12, HBD 4, PSA 226.28, QED 0.26
Compound (SMILES): Cc1cc(Oc2nccc3occc23)ccc1-c1c(C)ncc2nccn12
InChIKey: HWAIAGZSWHOLLK-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]-SCH23390 from human dopamine D1 receptor expressed in LTK cell membranes after 30 mins by liquid scintillation counting
Measurement: Ki = 21.6 nM (pChEMBL 7.670000076293945)
Descriptors: MW 356.39, ALogP 4.95, HBA 6, HBD 0, PSA 65.45, QED 0.46
Compound (SMILES): FC1(F)CC(Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: VURZKJCJGOOOFL-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 491.35, ALogP 5.32, HBA 7, HBD 2, PSA 88.51, QED 0.47
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: JWMKUJAOIPXYIG-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant in glioma patient-derived human TS603 neurosphere cells assessed as reduction in 2-HG content using alpha-ketoglutarate as substrate after 48 hrs by LC-MS analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 464.39, ALogP 5.15, HBA 6, HBD 2, PSA 75.62, QED 0.6
Compound (SMILES): Cn1cnc(-c2cc(-c3nn[nH]c3F)ccn2)c1-c1ccc(F)cc1OCC1CC1
InChIKey: KSVLYGYZCVITGZ-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: PHF8 Assay: The ability of test compounds to inhibit the activity of PHF8 was determined in 384-well plate format under the following reaction conditions: 3 nM PHF8, 200 nM H3K9me1-biotin labeled peptide (Anaspec cat #64358), 0.5 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified-histone H3 lysine 9/lysine27 (H3K9/K27) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 0.5 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 600 nM H3K9me1-biotin labeled peptide and 1.5 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 9 nM PHF8 to initiate the reaction. The reaction mixture was incubated at rt for 15 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 1 nM Europium-anti-unmodified H3K9/K27 antibody. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 408.41, ALogP 4, HBA 6, HBD 1, PSA 81.51, QED 0.52
Compound (SMILES): COc1ccc2c(c1)CCCC2Cn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: QGDZSZYNVSORDZ-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 rt for 40 min, 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 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 454.46, ALogP 4.88, HBA 6, HBD 1, PSA 81.51, QED 0.47
Compound (SMILES): CCNC(=S)NCC1CCc2ccc3ccc(OC)cc3c21
InChIKey: MLTPCDWECFSPOI-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at human MT2 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 314.45, ALogP 3.36, HBA 2, HBD 2, PSA 33.29, QED 0.85
Compound (SMILES): CC(F)(F)c1cc(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: RJZGABPOSOZJRY-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 501.41, ALogP 5.8, HBA 7, HBD 2, PSA 88.51, QED 0.41
Compound (SMILES): Oc1cc(Cc2ccc(Cl)cc2)nn1-c1cc(-c2nnn[nH]2)ccn1
InChIKey: KGEBIPZLKBPXBD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 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 the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 353.77, ALogP 2.4, HBA 7, HBD 2, PSA 105.4, QED 0.58
Compound (SMILES): COc1ccc(Cn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: OCDGBDZHGDKNCY-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 < 100 nM (pChEMBL 7)
Descriptors: MW 400.36, ALogP 3.81, HBA 6, HBD 1, PSA 81.51, QED 0.55
Compound (SMILES): CC(=O)N[C@H]1C[C@H]2O[C@@](C)([C@@H]1O)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: PTQKRNULLCXNRU-LCWSOADTSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of N-terminal His10-StrepII tagged human ROCK2 catalytic domain (1 to 553 residues) expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 480.52, ALogP 3.62, HBA 6, HBD 3, PSA 97.52, QED 0.34
Compound (SMILES): C[C@@H](Nc1nc(NCCOc2ccccc2)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: YVNVAIVKELSNHE-CQSZACIVSA-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 6 hrs before addition of alpha-KG followed by 60 mins 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 444.46, ALogP 4.65, HBA 7, HBD 2, PSA 84.85, QED 0.46
Compound (SMILES): CC(C)(N)C12CC3CC(CC(C3)C1)C2
InChIKey: NDDFDYJBIHXQIC-UHFFFAOYSA-N
Target: Matrix protein 2 (SINGLE PROTEIN), Influenza A virus
UniProt: P06821
Assay: Binding affinity to C-terminal amidated influenza A virus A/Udorn/72 (H3N2) M2 transmembrane domain (22 to 46 residues) in DPC micelles at pH 8 assessed as dissociation constant by ITC analysis
Measurement: Kd = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 193.33, ALogP 2.94, HBA 1, HBD 1, PSA 26.02, QED 0.68