lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3cn(S(C)(=O)=O)cn3)CC2)nc2ccsc12
InChIKey: MAZUVMQRDUXXOS-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase infected in human MT4 cells assessed as reduction in biotin-dUTP incorporation
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 537.67, ALogP 4.05, HBA 11, HBD 1, PSA 126.03, QED 0.37
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3csc(C(F)(F)F)n3)n2)CC1
InChIKey: PFTFOLWIPCINKJ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 498.47, ALogP 5.99, HBA 7, HBD 2, PSA 75.62, QED 0.49
Compound (SMILES): O=C(CCC(CCCC(=O)Nc1ccccc1)c1ccccc1)NO
InChIKey: CKQYXRXVDRHVDK-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 in human HeLa-S3 cell lysates preincubated for 15 mins followed by HDAC-Glo substrate addition measured after 30 to 40 mins by fluorimetric method
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 340.42, ALogP 3.86, HBA 3, HBD 3, PSA 78.43, QED 0.48
Compound (SMILES): C#CCNc1nc(NCCCC2CCN(Cc3ccccc3)CC2)c(C#N)cc1C#N
InChIKey: QDTPLCGSZPKZME-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAOA using tyramine hydrochloride as substrate preincubated for 30 mins followed by substrate addition measured for 1 hr by fluorometric method
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 412.54, ALogP 3.97, HBA 6, HBD 2, PSA 87.77, QED 0.48
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2cc(C(=O)O)ccc2F)c2ccccc12
InChIKey: PRQVEVLBUCMWDD-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Binding affinity to FABP4 (unknown origin) by isothermal calorimetric titration method
Measurement: Kd = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 375.38, ALogP 3.49, HBA 4, HBD 2, PSA 92.7, QED 0.71
Compound (SMILES): O=C(CCN1CCN(c2ncccn2)CC1)c1cc2c3c(c1)CCC(=O)N3CCC2
InChIKey: XMAJZXPBSHQXFR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserine from serotonin 5-HT2A receptor in rat brain cortex homogenates incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 557.4 nM (pChEMBL 6.25)
Descriptors: MW 405.5, ALogP 2.1, HBA 6, HBD 0, PSA 69.64, QED 0.71
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3cccc(F)c3)CC2)cc(C(C)(C)C)c1O
InChIKey: CTWWCIRKFWZLQA-ZHACJKMWSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A using p-tyramine as substrate incubated for 15 mins followed by substrate addition measured for 20 mins by fluorescence assay
Measurement: IC50 = 58400 nM (pChEMBL 4.230000019073486)
Descriptors: MW 494.7, ALogP 6.56, HBA 3, HBD 2, PSA 52.57, QED 0.43
Compound (SMILES): COc1c(Br)cccc1C(=O)Nc1cccc(Cl)c1
InChIKey: AWKNDZLXBMJPJB-UHFFFAOYSA-N
Target: Thiosulfate sulfurtransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16762
Assay: Inhibition of refolded rhodanese (unknown origin) preincubated with Escherichia coli GroEL/GroES for 60 mins in absence of compound followed by compound addition by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 340.6, ALogP 4.36, HBA 2, HBD 1, PSA 38.33, QED 0.9
Compound (SMILES): CC1CC(C(=O)Nc2nc3ccc(Cl)cc3s2)CC(C)(C)C1
InChIKey: NLJWGMYYULUAFJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 336.89, ALogP 5.35, HBA 3, HBD 1, PSA 41.99, QED 0.8
Compound (SMILES): COCCc1ccnc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: IIDRMKULCOPTDM-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 483.51, ALogP 4.5, HBA 8, HBD 2, PSA 97.74, QED 0.53
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(-c3cnn(C4CCNCC4)c3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: VHIPJRRFLDFKSD-CUWPLCDZSA-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 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 451.62, ALogP 4.3, HBA 8, HBD 3, PSA 92.82, QED 0.5
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCN(Cc3ccccc3)Cc3cn(CCOCCOc4ccc(-c5cc(=O)c6cc(F)ccc6o5)cc4)nn3)ccc12
InChIKey: UCQGLPGXMPPVIB-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 778.84, ALogP 8.14, HBA 11, HBD 0, PSA 122.06, QED 0.08
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3ccccc3Cl)CC2)cc(C(C)(C)C)c1O
InChIKey: IXKCDKJHBGONNW-VAWYXSNFSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using p-tyramine as substrate incubated for 15 mins followed by substrate addition measured for 20 mins by fluorescence assay
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 511.15, ALogP 7.07, HBA 3, HBD 2, PSA 52.57, QED 0.39
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCc3cccc4ccccc34)cn2)c1
InChIKey: HJHPUQDFLVHFFZ-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 343.39, ALogP 4.04, HBA 4, HBD 1, PSA 68.01, QED 0.59
Compound (SMILES): Cc1cccc(Cn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)c1F
InChIKey: LGVMSGMOXACFLZ-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 334.36, ALogP 3.23, HBA 5, HBD 1, PSA 72.28, QED 0.62
Compound (SMILES): Nc1sc2ccc(Cl)cc2c1Nc1ccc(F)cc1
InChIKey: ZAERAUPGIBHWPQ-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 292.77, ALogP 5.02, HBA 3, HBD 2, PSA 38.05, QED 0.7
Compound (SMILES): CC(Nc1nc(Nc2ccnc(C3(C#N)CC3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: HJCRKYCQHOQKKS-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 494.4, ALogP 5.01, HBA 8, HBD 2, PSA 112.3, QED 0.46
Compound (SMILES): FC1(F)CC(Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3nc(C(F)(F)F)cs3)n2)C1
InChIKey: FIHMFIIGBKKTHS-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 497.38, ALogP 5.38, HBA 8, HBD 2, PSA 88.51, QED 0.46
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CC4(C3)CC(F)(F)C4)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: RHCDZLRZYCRNDX-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 490.43, ALogP 5.54, HBA 6, HBD 2, PSA 75.62, QED 0.54
Compound (SMILES): O=C(O)c1ccnc(-n2nc(C3CC3)cc2O)c1
InChIKey: WEZPYYZPYXGXHK-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 245.24, ALogP 1.55, HBA 5, HBD 2, PSA 88.24, QED 0.86
Compound (SMILES): NC(=[Se])c1ccc(S(N)(=O)=O)cc1
InChIKey: CZIIHSLWIYNAMW-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 = 63.4 nM (pChEMBL 7.199999809265137)
Descriptors: MW 263.18
Compound (SMILES): FC1(F)CC2(CC(Nc3nc(Nc4ccnc(C(F)(F)F)c4)nc(-c4cncc(C(F)(F)F)n4)n3)C2)C1
InChIKey: UQNYKCNMQIBEFQ-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 532.4, ALogP 5.49, HBA 8, HBD 2, PSA 101.4, QED 0.42
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: NTKHRYLRDAXKRH-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 479.39, ALogP 5.31, HBA 7, HBD 2, PSA 99.41, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccc(Cl)cc3)n2-c2ccccc2)cc1
InChIKey: YXKRBFIZRCEMLB-FLFQWRMESA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by Lineweaver-Burk plot analysis
Measurement: Ki = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 441.97, ALogP 4.74, HBA 5, HBD 1, PSA 77.45, QED 0.5
Compound (SMILES): COc1cc2nccc(Nc3n[nH]c(C)c3C)c2cc1S(=O)(=O)C(C)(C)C
InChIKey: LHPFRDAGGDMRMZ-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: G3V783
Assay: Inhibition of RIPK2 in rat whole blood assessed as reduction in MDP-stimulated TNFalpha levels incubated for 30 mins followed by MDP addition measured after 5 hrs
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 388.49, ALogP 3.9, HBA 6, HBD 2, PSA 96.97, QED 0.7
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccccc3)n2-c2ccccc2)cc1
InChIKey: FXDROENCOYNWHS-LNVKXUELSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by Lineweaver-Burk plot analysis
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 407.52, ALogP 4.09, HBA 5, HBD 1, PSA 77.45, QED 0.55
Compound (SMILES): FC(F)c1cncc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: NNVCNVORYXXOAM-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 475.44, ALogP 5.25, HBA 7, HBD 2, PSA 88.51, QED 0.55
Compound (SMILES): COc1ccc(N(CCCCN2CCC(O)(c3ccc(Cl)c(C(F)(F)F)c3)CC2)c2ccc(OC)cc2)cc1
InChIKey: DYLSSJRMONSQGQ-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 = 729 nM (pChEMBL 6.139999866485596)
Descriptors: MW 563.06, ALogP 7.28, HBA 5, HBD 1, PSA 45.17, QED 0.26
Compound (SMILES): CC(C)Nc1nc(NC(C)C)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: WDSFOQJWJKBMPM-UHFFFAOYSA-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 340.35, ALogP 3.59, HBA 6, HBD 2, PSA 75.62, QED 0.87
Compound (SMILES): Fc1cc(F)c(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1F
InChIKey: MRBFFDHADFWESD-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 438.33, ALogP 4.41, HBA 5, HBD 1, PSA 72.28, QED 0.37
Compound (SMILES): C[C@@H](Nc1nc(NC(C(F)(F)F)C(F)(F)F)nc(-c2cccc(Cl)n2)n1)C(F)(F)F
InChIKey: VTJODCQTJUKOPV-RXMQYKEDSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 468.71, ALogP 4.85, HBA 6, HBD 2, PSA 75.62, QED 0.48
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCc4cc(F)ccc43)cn2)c1
InChIKey: VBYNYZPZKXJUEM-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 352.37, ALogP 2.85, HBA 5, HBD 1, PSA 71.25, QED 0.76
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H](Cc1ccc(Cl)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(C)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O
InChIKey: LAGYTFPAISIXPZ-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 677.21, ALogP 2.21, HBA 6, HBD 7, PSA 203.96, QED 0.09
Compound (SMILES): Cc1[nH]nc(N)c1-c1cccc(C(F)(F)F)c1
InChIKey: ZQARVLMZLATKQJ-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 241.22, ALogP 2.99, HBA 2, HBD 2, PSA 54.7, QED 0.81
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)CC1
InChIKey: TZKFRDJJAGMBLQ-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 478.42, ALogP 5.54, HBA 6, HBD 2, PSA 75.62, QED 0.55
Compound (SMILES): C#Cc1cccc2c(OC(=O)[C@H]3[C@@H](c4ccccc4)[C@H](C(=O)O)[C@@H]3c3ccccc3)cccc12
InChIKey: FUPGSWJNOVXUBI-LJWNLINESA-N
Target: Fatty acid-binding protein, brain (SINGLE PROTEIN), Homo sapiens
UniProt: O15540
Assay: Displacement of ANS from recombinant human N-terminal His-tagged FABP7 expressed in Escherichia coli BL21(DE3) after 20 mins by fluorescence assay
Measurement: Ki = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 446.5, ALogP 5.62, HBA 3, HBD 1, PSA 63.6, QED 0.25
Compound (SMILES): COc1ccc2ccc3c(c2c1)C(CNC(C)=O)CC3
InChIKey: VABVTFAPCKMYHN-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 269.34, ALogP 3.01, HBA 2, HBD 1, PSA 38.33, QED 0.93
Compound (SMILES): CNc1ncc(C(=O)OC(C)C)c2nc(-c3ccco3)nn12
InChIKey: LPCDJQHFMKVKPZ-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 = 2.75 nM (pChEMBL 8.5600004196167)
Descriptors: MW 301.31, ALogP 1.99, HBA 8, HBD 1, PSA 94.55, QED 0.74
Compound (SMILES): Nc1nc2oc3ccc(C4CCSCC4)cc3c(=O)c2cc1C(=O)O
InChIKey: XVFXLPHBPBGJMX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Kinase Assays: Kinase assays are commonly used for determining the ability of a small molecule to inhibit enzyme activity. By measuring the degree of phosphorylation of a substrate at varying concentrations of inhibitor, the concentration of inhibitor resulting in 50% enzymatic activity (IC50) can be obtained. The IC50 is defined as the inflection point of the sigmoidal graph obtained when plotting substrate phosphorylation vs. inhibitor concentration. Experiments were conducted during development of embodiments herein using radiolabeled ATP to detect substrate phosphorylation in the presence of amlexanox analogs to determine the potency (IC50) of said analogs.TBK1 (residues 1-657) and IKKε (residues 1-655) were purified from insect cells to ≥90% purity by coomassie staining. Reactions containing 50 nM TBK1 or IKKε, 7 μM myelin basic protein (MBP), and inhibitor in reaction buffer (50 mM HEPES pH 7.5, 10 mM NaCl, 10 mM MgCl2, 1 mM DTT) were initiated with 5 μM ATP spiked with [γ-32P]-ATP and allowed to proceed for 30 minutes at room temperature. Reactions were quenched with SDS gel loading dye, run on 4-15% SDS-PAGE gels, and imaged on phosphorimaging screens. Band intensities corresponding to phosphorylated MBP were quantified with ImageQuant and the data analyzed in Prism 6. Dose-response assay band intensities were normalized and fit to a sigmoidal dose-response equation with the Hill slope fixed at −1 and the top constrained to 100.
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 356.4, ALogP 3.23, HBA 6, HBD 2, PSA 106.42, QED 0.68
Compound (SMILES): CCCCCCCCCCCCC/C(=N\O)c1cc(-c2ccc(O)c(F)c2)ccc1O
InChIKey: HDOKJCNJHOXSDX-ZZIIXHQDSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of recombinant human ABHD6 expressed in HEK293 cells using 2-OG as substrate pretreated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.58, ALogP 7.78, HBA 4, HBD 3, PSA 73.05, QED 0.12
Compound (SMILES): CCCCc1ccc(NC(=O)Nc2cc(S(N)(=O)=O)ccc2O)cc1
InChIKey: KIUMBSMJLUNPQP-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 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 363.44, ALogP 3.03, HBA 4, HBD 4, PSA 121.52, QED 0.59
Compound (SMILES): Nc1ccccc1NC(=O)CCCCCCC(=O)Nc1ccc(-c2cn(Cc3ccccc3)nn2)cc1
InChIKey: IYKIQDXPWYJSPM-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using (FAM)-labeled acetylated peptide as substrate measured after 17 hrs by fluorescence assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 496.62, ALogP 5.49, HBA 6, HBD 3, PSA 114.93, QED 0.18
Compound (SMILES): COc1ccc(CNc2ncc(C(=O)NC(c3ccccc3)c3ccccc3)c3nc(-c4ccco4)nn23)cc1OC
InChIKey: MWOWEAQGGNMMNY-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 = 69.9 nM (pChEMBL 7.159999847412109)
Descriptors: MW 560.61, ALogP 5.53, HBA 9, HBD 2, PSA 115.81, QED 0.22
Compound (SMILES): CCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCc3ccccc3)cc2)n(CCC)c1=O
InChIKey: SLOCEKSXBYIFCC-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 558.68, ALogP 3.33, HBA 9, HBD 1, PSA 103.39, QED 0.29
Compound (SMILES): FC1(F)CC(Nc2nc(NC3CC(F)(F)C3)nc(-c3nccc(C(F)(F)F)n3)n2)C1
InChIKey: FPHDGFLOXFTVGJ-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): COc1ccc2[nH]cc(CCNC(=O)[C@H](Cc3ccncc3)NC(=O)[C@H](Cc3ccc(Cl)cc3)NC(=O)[C@H](Cc3c[nH]c4ccc(O)cc34)NC(=O)CCCN)c2c1
InChIKey: SRCCZHZOKZJHOK-IGMOWHQGSA-N
Target: Ephrin type-A receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54764
Assay: Binding affinity to EphA4 ligand binding domain (unknown origin) by ITC
Measurement: Kd = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 807.35, ALogP 3.99, HBA 8, HBD 8, PSA 216.35, QED 0.06
Compound (SMILES): Cc1nn(C(=O)[C@H](C)c2ccc(CC(C)C)cc2)c(C)c1Cl
InChIKey: RFAYOJJBVSPOFY-GFCCVEGCSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Inhibition of human TNAP expressed in COS7 cells using CDP-star as substrate preincubated for 5 to 10 mins followed by substrate addition measured after 20 mins by luminescence-based assay
Measurement: IC50 = 1070 nM (pChEMBL 5.96999979019165)
Descriptors: MW 318.85, ALogP 4.8, HBA 3, HBD 0, PSA 34.89, QED 0.81
Compound (SMILES): NC(=O)c1cnc2c(N[C@H]3C[C@H]3F)cc(Nc3cccc(-c4ccc(C(F)(F)F)cc4F)c3)nn12
InChIKey: UMHAGOZMLWBAGB-SJORKVTESA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Displacement of [3H]-c-AMP from His-Tb-tagged human PDE4D2 (86 to 413 residues) preincubated for 10 mins followed by [3H]-c-AMP addition measured after 1 hr by scintillation proximity assay
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 488.42, ALogP 4.92, HBA 6, HBD 3, PSA 97.34, QED 0.34
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCCc3cn(CCOCCOCCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)nn3)ccc12
InChIKey: JFQGPWJJYPFSFY-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 515 nM (pChEMBL 6.289999961853027)
Descriptors: MW 699.76, ALogP 6.95, HBA 11, HBD 0, PSA 128.05, QED 0.09
Compound (SMILES): NS(=O)(=O)c1cc(NC(=O)NCc2ccco2)c(O)c([N+](=O)[O-])c1
InChIKey: XIEOWAXTWJTGQW-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of carbonic anhydrase 12 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 356.32, ALogP 0.86, HBA 7, HBD 4, PSA 177.8, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(C[Te]c3ccccc3)[se]2)cc1
InChIKey: XIBJCSLHJGQWSV-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 = 56.3 nM (pChEMBL 7.25)
Descriptors: MW 504.93
Compound (SMILES): CCC(Nc1nc(NC(CC)C(F)(F)F)nc(-c2cccc(Cl)n2)n1)C(F)(F)F
InChIKey: SDUBFPITPDQUSW-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 442.8, ALogP 5.09, HBA 6, HBD 2, PSA 75.62, QED 0.46
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-n3ccc(C(F)(F)F)n3)n2)c1
InChIKey: GOMGSGWMVHCJSA-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 468.37, ALogP 4.43, HBA 8, HBD 2, PSA 104.34, QED 0.53
Compound (SMILES): CC(C#N)Nc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: DOYNKYWVGHFSIP-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 450.38, ALogP 4.53, HBA 8, HBD 2, PSA 112.3, QED 0.53
Compound (SMILES): Nc1oc2cnccc2c1Nc1cccc(F)c1
InChIKey: RDAVYNWFTYZCHG-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 243.24, ALogP 3.29, HBA 4, HBD 2, PSA 64.08, QED 0.72
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)[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: LJWQJIJAFSXBTK-GONAQTSYSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 3200 nM (pChEMBL 5.5)
Descriptors: MW 4064.54
Compound (SMILES): CN(c1ncnc2[nH]ccc12)[C@H]1CN(S(=O)(=O)c2cccc(C#N)c2)CC12CC2
InChIKey: DHEBFJJCQBLOPI-KRWDZBQOSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human TYK2 using GGMEDIYFEFMGGKKK as substrate after 40 mins in presence of [gamma-33P-ATP] by scintillation counting method
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 408.49, ALogP 2.12, HBA 6, HBD 1, PSA 105.98, QED 0.71
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N/N=C/c2ccc(N3CCN(C(=O)c4ccco4)CC3)cc2)cc1
InChIKey: CIWLILAMCOWUAO-PCLIKHOPSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as CO2 hydration preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye-based stopped-flow assay
Measurement: Ki = 30.4 nM (pChEMBL 7.519999980926514)
Descriptors: MW 481.53, ALogP 1.65, HBA 7, HBD 2, PSA 138.31, QED 0.41
Compound (SMILES): CC(=O)N1CCN([C@H]2CC[C@H](Nc3ncnn4ccc([C@H](C)CC(N)=O)c34)CC2)CC1
InChIKey: RGHNWSCEPVZMFH-KBAYOESNSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human KARPAS299 cells assessed as reduction in IL-1 stimulated IRAK4 phosphorylation at Thr345/Ser346 residues preincubated for 1 hr followed by IL-1 stimulation for 10 mins by flow cytometry analysis
Measurement: IC50 = 141.25 nM (pChEMBL 6.849999904632568)
Descriptors: MW 427.55, ALogP 1.6, HBA 7, HBD 2, PSA 108.86, QED 0.72
Compound (SMILES): NC(=O)c1cnc2c(NC3CC3)cc(Nc3ccccc3)nn12
InChIKey: QZGWYLPGPJWINC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 JH2 domain (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 308.35, ALogP 2.15, HBA 6, HBD 3, PSA 97.34, QED 0.67
Compound (SMILES): Cc1nn(-c2cc(C(=O)O)ccn2)c(O)c1-c1ccccc1
InChIKey: VMLMHVMQZCMCBR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in Escherichia coli using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 295.3, ALogP 2.65, HBA 5, HBD 2, PSA 88.24, QED 0.78
Compound (SMILES): Cc1cc(C)c(Nc2ccnc(Nc3ccc(Cl)cc3)n2)c(C)c1
InChIKey: UKMJJMHWYKEQMZ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant HIV1 reverse transcriptase Y181C mutant
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 338.84, ALogP 5.54, HBA 4, HBD 2, PSA 49.84, QED 0.66
Compound (SMILES): CC[N+](CC)(CC)CCCCCCOc1ccc(/C=C/c2ccccc2)cc1.[I-]
InChIKey: FXBKAVKFPWOCQQ-CMBBICFISA-M
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Antagonist activity at human alpha9alpha10 nACHR expressed in xenopous laevis oocyte assessed as inhibition of ACh-induced channel current after 5 mins at -70 mV holding potential by two electrode voltage clamp method
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 380.6, ALogP 6.67, HBA 1, HBD 0, PSA 9.23, QED 0.21
Compound (SMILES): C[C@@H](Nc1nc(N[C@H](C)C2CC2)nc(-n2ccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: ZFCNVKABVPLJJM-NXEZZACHSA-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 381.41, ALogP 3.5, HBA 7, HBD 2, PSA 80.55, QED 0.76
Compound (SMILES): CC(F)(F)c1cccc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: YRSZQQILDIHZRT-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 432.37, ALogP 4.46, HBA 6, HBD 2, PSA 75.62, QED 0.66
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1n[nH]nc1O
InChIKey: CTPZCVRODHKARO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of human NIK using AKDVDQGSLCTSFVGTLQY as substrate after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 340.18, ALogP 2.8, HBA 4, HBD 3, PSA 90.9, QED 0.73
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ncc(-c3ccccc3)[se]2)cc1
InChIKey: FMNYHPPTHRSLST-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 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 363.3
Compound (SMILES): Fc1cccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c1
InChIKey: BBWOOOREENNAAQ-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 402.36, ALogP 4.13, HBA 5, HBD 1, PSA 72.28, QED 0.51
Compound (SMILES): CCCCN1C(=O)C(=NNC(=O)c2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: QSUZYQZAQILTBO-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 = 44.1 nM (pChEMBL 7.360000133514404)
Descriptors: MW 400.46, ALogP 1.61, HBA 5, HBD 2, PSA 121.93, QED 0.72
Compound (SMILES): Cc1cc(Cn2c(=O)n(Cc3cnn(C)c3)c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc32)n(C)n1
InChIKey: OVZCFDSZHNYEBG-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 497.58, ALogP 0.87, HBA 10, HBD 1, PSA 125.81, QED 0.4
Compound (SMILES): N#Cc1cc(F)cc(Nc2nc(NCC3CC3)nc(-c3cccc(C(F)(F)F)n3)n2)c1
InChIKey: MVIKPHSCGJFANI-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 429.38, ALogP 4.53, HBA 7, HBD 2, PSA 99.41, QED 0.56
Compound (SMILES): NC(=O)c1ccc(OCc2cccc(Br)c2)cc1
InChIKey: WNYIDDKTEYNPSM-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N5
Assay: Inhibition of PARP14 (unknown origin) using NAD+ as substrate incubated for 18 hrs by fluorescence based assay
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 306.16, ALogP 3.13, HBA 2, HBD 1, PSA 52.32, QED 0.94
Compound (SMILES): CC1(NC#N)CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: PTCVBQDKOCSZKC-UHFFFAOYSA-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 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 289.34, ALogP 2.86, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)c(Cl)c1)c1cccc(Br)c1
InChIKey: JXAKOAQJURHBQY-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 475.82, ALogP 7.12, HBA 4, HBD 1, PSA 41.99, QED 0.34
Compound (SMILES): COc1cc2[nH]c(C(=O)NCCC3CCN(Cc4ccccc4)CC3)cc(=O)c2cc1OC
InChIKey: FYEQJLDNQJUZMM-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human 5-lipoxygenase using arachidonic acid as substrate pretreated for 10 mins followed by substrate and ATP addition and measured after 20 mins by H2DCFDA probe based fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 449.55, ALogP 3.58, HBA 5, HBD 2, PSA 83.66, QED 0.55
Compound (SMILES): COCCOc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: ZSYSQOMASXIARJ-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 403.82, ALogP 3.22, HBA 7, HBD 1, PSA 95.7, QED 0.55
Compound (SMILES): OCC1CCCC(c2ccc(O)cc2)CC1
InChIKey: TYZPZHWTUNATHL-UHFFFAOYSA-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 = 99 nM (pChEMBL 7)
Descriptors: MW 220.31, ALogP 3.05, HBA 2, HBD 2, PSA 40.46, QED 0.75