lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Fc1ccc(-c2c(-c3cc(-c4nn[nH]n4)ccn3)ncn2Cc2ccccc2Cl)cc1
InChIKey: BRSDWTFJHHGKFU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 431.86, ALogP 4.63, HBA 6, HBD 1, PSA 85.17, QED 0.44
Compound (SMILES): Cn1nc(C(N)=O)c2c1-c1nc(Nc3ccc(N4CCNCC4)cn3)ncc1CC2
InChIKey: PNPPYTKHXUSEOA-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 405.47, ALogP 0.62, HBA 9, HBD 3, PSA 126.88, QED 0.58
Compound (SMILES): CCCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCCc3ccccn3)cc2)n(CCCC)c1=O
InChIKey: CCABRZUAUMFZGC-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-602 from human adenosine A2B receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 601.75, ALogP 3.55, HBA 10, HBD 1, PSA 116.28, QED 0.22
Compound (SMILES): Cc1cc(F)cc(Nc2cc(NC3CC3)c3ncc(C(N)=O)n3n2)c1
InChIKey: OLBDEEXDXLJJDK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 JH1 domain (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 340.36, ALogP 2.59, HBA 6, HBD 3, PSA 97.34, QED 0.66
Compound (SMILES): CC(C#N)Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: YBMLCUNTUFVOKD-QVDQXJPCSA-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 377.37, ALogP 3.49, HBA 7, HBD 2, PSA 99.41, QED 0.79
Compound (SMILES): NS(=O)(=O)c1ccc(/N=c2\scc(-c3ccc(Br)cc3)n2-c2ccccc2)cc1
InChIKey: GXAZOLWZTDWYPB-FLFQWRMESA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by Lineweaver-Burk plot analysis
Measurement: Ki = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 486.42, ALogP 4.85, HBA 5, HBD 1, PSA 77.45, QED 0.45
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCn4ncnc4C3)n2c1)S(C)(=O)=O
InChIKey: CMESULMYHLFNCB-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 506.42, ALogP 3.31, HBA 8, HBD 0, PSA 88.63, QED 0.41
Compound (SMILES): Cc1[nH]nc(Nc2ccnc3cc(OCCO)c(S(=O)(=O)C(C)(C)C)cc23)c1C
InChIKey: HRBKEPLXBIHJME-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells by Qpatch clamp assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 418.52, ALogP 3.26, HBA 7, HBD 3, PSA 117.2, QED 0.56
Compound (SMILES): CCN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)Cc1ccc(F)cc1
InChIKey: APXJVQHWHOFBFC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 368.41, ALogP 3.3, HBA 5, HBD 1, PSA 71.25, QED 0.66
Compound (SMILES): Cc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)c(C)c1
InChIKey: ZQNXWEZQRNBWCU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 323.35, ALogP 3.16, HBA 5, HBD 1, PSA 77.24, QED 0.78
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)NC(=O)NC3=O)cc(OCC)c1-c1ccc(F)cc1
InChIKey: WILOTRUGSQCRHL-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Antagonist activity at human SSTR5 expressed in CHO-K1 cell membranes assessed as reduction in SST-28-induced inhibition of forskolin-stimulated cAMP accumulation by LANCE assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 441.5, ALogP 3.46, HBA 5, HBD 2, PSA 79.9, QED 0.64
Compound (SMILES): Cn1cnc(-c2cc3[nH]nnc3cn2)c1-c1ccc(F)cc1OCC1CC1
InChIKey: IJEOCHNJDZZTLK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 364.38, ALogP 3.35, HBA 6, HBD 1, PSA 81.51, QED 0.59
Compound (SMILES): CC(=O)N1CCN(c2ccc(CO[C@H]3CO[C@](Cn4ccnc4)(c4ccc(Cl)cc4Cl)OC3)cc2)CC1
InChIKey: QVYYCUHPBMNBTJ-HNKWHGCMSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of CYP19 (unknown origin)
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 545.47, ALogP 4.34, HBA 7, HBD 0, PSA 69.06, QED 0.44
Compound (SMILES): CC(C)(C)C1CCC(C(=O)N2CCC(C(=O)Nc3ccccc3)CC2)CC1
InChIKey: HTLIMAONQZGNCN-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Antagonist activity at human Gal4-fused RXRgamma expressed in HEK293T cells assessed as inhibition of bexarotene-induced transactivation after 12 to 14 hrs by dual-Glo luciferase reporter gene assay
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 370.54, ALogP 4.72, HBA 2, HBD 1, PSA 49.41, QED 0.84
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2cccc(O)c2)c1
InChIKey: SCDSPJVQVVSKER-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 311.3, ALogP 2.25, HBA 6, HBD 2, PSA 97.47, QED 0.75
Compound (SMILES): CCCc1nccc2c(Nc3ccc(F)c(C(F)(F)F)c3)c(N)oc12
InChIKey: NCDWXIQRAXAGRM-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 353.32, ALogP 5.26, HBA 4, HBD 2, PSA 64.08, QED 0.63
Compound (SMILES): FC(F)(F)c1[nH]nnc1-c1ccnc(-c2cn(Cc3ccc(Cl)cc3)cn2)c1
InChIKey: UPFBFWHBHKNIFJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 404.78, ALogP 4.45, HBA 5, HBD 1, PSA 72.28, QED 0.55
Compound (SMILES): O=C1CCC2CN(Cc3c(-c4ccc(Cl)cc4)nc4cnc(C5CC5)cn34)CCN12
InChIKey: BZYOEBWCELTDFC-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 421.93, ALogP 3.73, HBA 5, HBD 0, PSA 53.74, QED 0.64
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(N)=O
InChIKey: SOPPRTLDAJBUPO-MPFIPSHNSA-N
Target: Envelope glycoprotein gp160 (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q6QLK5
Assay: Inhibition of gp41 V38M mutant in T20-resistant HIV1 NL4-3 assessed as inhibition of viral infection in Ghost (3)X4/R5 cells after 48 hrs by Bright-Glo luciferase reporter gene assay
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 3126.63
Compound (SMILES): CCN1CCC(c2ccc(Nc3ncc(F)c(-c4ccc5c(c4)C(C)(CC)C(C)=N5)n3)nc2)CC1
InChIKey: GZUIGXOHHAYCLT-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin-D3 (unknown origin) using histoneH1 as substrate after 90 mins by ADP-Glo assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 472.61, ALogP 6.39, HBA 6, HBD 1, PSA 66.3, QED 0.45
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCN(c4ccccn4)C3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: TYLCUGJKUXBFOZ-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 506.48, ALogP 4.64, HBA 8, HBD 2, PSA 91.75, QED 0.47
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H](Cc1ccc(F)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(C)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(N)=O
InChIKey: KYDKNSTYQUOGNQ-ZXYZSCNASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK293 cells after 3 mins by cAMP assay
Measurement: EC50 = 315 nM (pChEMBL 6.5)
Descriptors: MW 660.75, ALogP 1.69, HBA 6, HBD 7, PSA 203.96, QED 0.09
Compound (SMILES): O=C(Nc1cccc(Cl)c1)c1cc(Br)cc(Br)c1
InChIKey: NWALRZLSERJAHI-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 389.47, ALogP 5.12, HBA 1, HBD 1, PSA 29.1, QED 0.76
Compound (SMILES): O=C(O)[C@H]1[C@H](c2ccccc2)[C@H](C(=O)OC2CCCCC2)[C@H]1c1ccccc1
InChIKey: KVRPLCLCJWQZCI-CMOCDZPBSA-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 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 378.47, ALogP 4.76, HBA 3, HBD 1, PSA 63.6, QED 0.76
Compound (SMILES): FC(F)(F)c1cccc(Cn2cnc(-c3cc(-c4nn[nH]n4)ccn3)c2)c1Cl
InChIKey: IWXQPCTUWUKXSM-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.77, ALogP 3.85, HBA 6, HBD 1, PSA 85.17, QED 0.56
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc(C)n(C(C)C)c5c4)n3)nc2)CC1.CS(=O)(=O)O
InChIKey: NCJPFQPEVDHJAZ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 506.61, ALogP 4.94, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): OCCC1CCCC(c2ccc(O)cc2)CC1
InChIKey: ZOGLPNHOAMLKAP-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at full length ERalpha (unknown origin) after 24 hrs by ERE-driven luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 234.34, ALogP 3.44, HBA 2, HBD 2, PSA 40.46, QED 0.79
Compound (SMILES): CC(=O)OCn1nnc(-c2ccnc(-c3cn(Cc4ccccc4Cl)cn3)c2)n1
InChIKey: NPCGMBQJXHGUQX-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 409.84, ALogP 2.82, HBA 9, HBD 0, PSA 100.61, QED 0.45
Compound (SMILES): CNc1ncc(C(=O)OC(c2ccccc2)c2ccccc2)c2nc(-c3ccco3)nn12
InChIKey: JPJGTQKFWIRNKU-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 425.45, ALogP 4.37, HBA 8, HBD 1, PSA 94.55, QED 0.4
Compound (SMILES): Nc1nc2oc3ccc(C4CCOCC4)cc3c(=O)c2cc1C(=O)O
InChIKey: SXKYBRCNSCMDKA-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 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 340.34, ALogP 2.52, HBA 6, HBD 2, PSA 115.65, QED 0.69
Compound (SMILES): C[C@H](NC(=O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)N[C@@H](C[C@@]1(O)C(=O)N(C)c2ccccc21)C(=O)NCc1ccccc1
InChIKey: HEQRQLIBQWIZNV-DJKIMAOQSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S immunoproteasome beta-1 using Ac-PAL-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 763.89, ALogP 4.26, HBA 8, HBD 5, PSA 175.4, QED 0.12
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCn3cccn3)cn2)c1
InChIKey: FJDQJUPBHKHILS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 283.29, ALogP 1.54, HBA 6, HBD 1, PSA 85.83, QED 0.77
Compound (SMILES): COc1cccc(Nc2c(N)sc3ccccc23)c1
InChIKey: NHDHUVDEZUIPNE-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 270.36, ALogP 4.24, HBA 4, HBD 2, PSA 47.28, QED 0.75
Compound (SMILES): COc1nc(-c2ccnc(NC(=O)C3CC3)c2)sc1C(=O)NCCCCCCNc1c2c(nc3ccccc13)CCCC2
InChIKey: BHHVWPMBOQGGMM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human full length N-terminal GST-tagged GSK-3beta expressed in Sf9 insect cells using prephosphorylated polypeptide as substrate after 30 mins by kinase-Glo reagent based luminescence assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 598.77, ALogP 6.39, HBA 8, HBD 3, PSA 118.13, QED 0.15
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C(=O)Nc3ccc(F)cc3)c(F)c2)cc1
InChIKey: JCIWZUTVGHDCLP-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: Transrepression of recombinant mouse GAL4-DBD fused RORgammat LBD expressed in HEK293 cells after 20 hrs by luciferase reporter gene assay
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 500.57, ALogP 4.86, HBA 4, HBD 2, PSA 92.34, QED 0.46
Compound (SMILES): CC(=O)/C=C1\C(=O)Nc2ccc(Cl)cc21
InChIKey: NGBDRYCUEWUGNM-WTKPLQERSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 assessed as reduction in conversion of L-tryptophan to kynurenine by methylene blue dye based spectrometric method
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 221.64, ALogP 2.26, HBA 2, HBD 1, PSA 46.17, QED 0.74
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N(C)[C@@H](C)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: XXNQZYMWEVTMER-DNZVHFOBSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 4007.49
Compound (SMILES): N#Cc1ccc2c(Nc3cccc(Br)c3)c(N)oc2c1
InChIKey: JPHADCMFHNLEBX-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 328.17, ALogP 4.39, HBA 4, HBD 2, PSA 74.98, QED 0.73
Compound (SMILES): CC(=O)CNc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: GZYMCQBNCUYDKE-SNVBAGLBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 380.37, ALogP 3.16, HBA 7, HBD 2, PSA 92.69, QED 0.76
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(F)cc2OCc2ccc(F)cc2)c1
InChIKey: YMWREFXLGWZZOR-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 437.4, ALogP 4.4, HBA 6, HBD 1, PSA 86.47, QED 0.44
Compound (SMILES): CC1(C)CCS(=O)(=O)c2ccc(CN3CCC4(CC3)CN(c3ccc(C(=O)O)cc3)C(=O)O4)cc21
InChIKey: WTDHYTDCEHHSPS-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse SSR5 expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition measured after 1 hr by LANCE assay
Measurement: IC50 = 283 nM (pChEMBL 6.550000190734863)
Descriptors: MW 498.6, ALogP 3.83, HBA 6, HBD 1, PSA 104.22, QED 0.68
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-n3ccc(C(F)(F)F)n3)n2)CC1
InChIKey: SLPLEYMIEBFOSW-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 481.42, ALogP 5.06, HBA 7, HBD 2, PSA 80.55, QED 0.58
Compound (SMILES): CC(C)=CCc1c(O)ccc(C(=O)[C@@H]2[C@@H](c3ccc(O)cc3O)CC(C)=C[C@H]2c2c(O)cc(O)c3c(=O)c(CC=C(C)C)c(-c4ccc(O)cc4O)oc23)c1O
InChIKey: DKBPTKFKCCNXNH-JMBMPLIVSA-N
Target: Phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: A0A045ISB3
Assay: Binding affinity to Mycobacterium tuberculosis PtpB by UV-VIS spectrophotometric analysis
Measurement: Kd = 1000 nM (pChEMBL 6)
Descriptors: MW 760.84, ALogP 8.84, HBA 11, HBD 8, PSA 209.12, QED 0.05
Compound (SMILES): C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCc1ccccc1
InChIKey: LSNJZAZKQQKEFV-OGWZEYOOSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S immunoproteasome beta-1 using Ac-PAL-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 530.58, ALogP 2.33, HBA 6, HBD 5, PSA 145.86, QED 0.27
Compound (SMILES): O=c1cc(-c2ccc(OCCOCCn3cc(CCCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)nn3)cc2)oc2ccccc12
InChIKey: DRMQFLGLGDRMMU-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP in human MCF7/MX100 cells assessed as reversal of topotecan resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 29.5 nM (pChEMBL 7.53000020980835)
Descriptors: MW 655.71, ALogP 6.93, HBA 10, HBD 0, PSA 118.82, QED 0.11
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)cc2C(F)F)nc(N2CCOC[C@H]2C)n1
InChIKey: PUBXMMWSRUCMJH-VXGBXAGGSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to recombinant human GST-tagged mTOR catalytic domain (1360 to 2549 residues) expressed in baculovirus after 1 hr by TR-FRET displacement assay
Measurement: Ki = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 421.45, ALogP 1.9, HBA 9, HBD 1, PSA 102.52, QED 0.79
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCOCCOCCn3cc(COCCOc4ccc5c(=O)cc(-c6ccccc6)oc5c4)nn3)ccc12
InChIKey: YZTDGFBYXAVFSO-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 715.76, ALogP 6.53, HBA 12, HBD 0, PSA 137.28, QED 0.09
Compound (SMILES): C[C@](O)(CO)CNc1cc(Nc2cccc(-c3ccc(C(F)(F)F)cc3F)c2)nn2c(C(N)=O)cnc12
InChIKey: FFPOZDPMXNQPOH-HSZRJFAPSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 domain in IFNalpha-stimulated human Kit225 T cells by luciferase reporter assay
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 518.47, ALogP 3.55, HBA 8, HBD 5, PSA 137.8, QED 0.23
Compound (SMILES): CC(C)(C)c1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1
InChIKey: QTABKBZRAZXDQK-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of GST tagged-TEV cleavage site-fused human recombinant TNKS2 (873 to 1166 residues) expressed in baculovirus infected sf9 cells assessed as reduction in auto-PARsylation incubated for 60 mins in presence of bio-NAD as co-substrate by ELISA
Measurement: IC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 278.36, ALogP 3.89, HBA 2, HBD 1, PSA 45.75, QED 0.73
Compound (SMILES): COc1ccc([Te]Cc2cnc(-c3ccc(S(N)(=O)=O)cc3)[se]2)cc1
InChIKey: XZYKSCRUSASMEE-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 853.9 nM (pChEMBL 6.070000171661377)
Descriptors: MW 534.95
Compound (SMILES): COc1ccc(F)c(-c2nc(N[C@H](C)C3CC3)nc(N[C@H](C)C3CC3)n2)c1
InChIKey: WWRAJFZRAVDBHX-VXGBXAGGSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 371.46, ALogP 4.11, HBA 6, HBD 2, PSA 71.96, QED 0.73
Compound (SMILES): C[C@@H](Nc1nc(Nc2ccnc(-c3ccc(Cl)cc3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: IETQZYOXYCRTPQ-GFCCVEGCSA-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 539.87, ALogP 6.77, HBA 7, HBD 2, PSA 88.51, QED 0.26
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3Cc4ccc(F)cc4C3)cn2)c1
InChIKey: ZGPYPJSEAHWBHB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 352.37, ALogP 2.8, HBA 5, HBD 1, PSA 71.25, QED 0.76
Compound (SMILES): O=c1cc(-c2ccc(OCCOCCn3cc(CN(Cc4ccccc4)Cc4cn(CCOCCOc5ccc(-c6cc(=O)c7ccccc7o6)cc5)nn4)nn3)cc2)oc2ccccc12
InChIKey: ZXMKYCZBSYKRII-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 885.98, ALogP 7.81, HBA 15, HBD 0, PSA 162, QED 0.06
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCCC3=O)cn2)c1
InChIKey: YPVNFSOVJOZZTM-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 300.32, ALogP 1.27, HBA 5, HBD 1, PSA 88.32, QED 0.9
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCCc4cc(Cl)ccc43)cn2)c1
InChIKey: HNQJHFKEFOZLKD-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 382.85, ALogP 3.75, HBA 5, HBD 1, PSA 71.25, QED 0.73
Compound (SMILES): CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccccc1c2/C=N/OCCCCCC(=O)NCCSSCCNC(=O)/C(Cc1ccc(O)c(Br)c1)=N\O
InChIKey: WZSUYCUMWMYLBJ-YPXMTRNESA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using RHKK(Ac)AMC as substrate after 1 to 2 hrs by fluorescence assay
Measurement: IC50 = 709 nM (pChEMBL 6.150000095367432)
Descriptors: MW 895.85, ALogP 5.15, HBA 15, HBD 5, PSA 214.03, QED 0.02
Compound (SMILES): Nc1oc2cnc(F)cc2c1Nc1cccc(Cl)c1
InChIKey: SCCDLKUDWOTTKU-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 277.69, ALogP 3.95, HBA 4, HBD 2, PSA 64.08, QED 0.7
Compound (SMILES): CNC(=O)C[C@@H](C)c1ccn2ncnc(N[C@H]3CC[C@H](N4CCN(C(=O)OC)CC4)CC3)c12
InChIKey: JFKJGBXGNSAENV-KZNAEPCWSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant full length His-tagged human IRAK4 expressed in baculovirus expression system using 5-FAM-IPTSPITTTYFFFKKK-COOH as substrate after 240 mins in presence of ATP by mobility shift assay
Measurement: IC50 = 208.93 nM (pChEMBL 6.679999828338623)
Descriptors: MW 457.58, ALogP 2.08, HBA 8, HBD 2, PSA 104.1, QED 0.68
Compound (SMILES): O=C(O)c1ccc2ccc(C(=O)c3ccccc3)c-2cc1
InChIKey: BIVIZHDMMVXLLG-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 276.29, ALogP 3.72, HBA 2, HBD 1, PSA 54.37, QED 0.74
Compound (SMILES): CC(=O)N1CCN([C@H]2CC[C@H](Nc3ncnn4ccc(C5CCOCC5)c34)CC2)CC1
InChIKey: SWPXADMCNLNAGW-MXVIHJGJSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of recombinant human N-terminal His6-tagged full length IRAK4 expressed in baculovirus infected Sf21 insect cells in presence of 5000 uM ATP
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 426.57, ALogP 2.51, HBA 7, HBD 1, PSA 75, QED 0.81
Compound (SMILES): CCS(=O)(=O)N(C)c1ccc2nc(-c3ccc(Cl)cc3)c(CN3CCN(C(C)=O)CC3)n2c1
InChIKey: CTPVKHUSMWKLJR-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 490.03, ALogP 3.1, HBA 6, HBD 0, PSA 78.23, QED 0.53
Compound (SMILES): Cc1coc2c1c(=O)oc(=O)c1c3c(ccc12)C(C)(C)CCC3
InChIKey: AZZOSPOHDDQAFO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE using butyrylhiocholine as substrate
Measurement: IC50 = 7883 nM (pChEMBL 5.099999904632568)
Descriptors: MW 310.35, ALogP 3.82, HBA 4, HBD 0, PSA 60.42, QED 0.63
Compound (SMILES): O/N=C1\CCCC(c2ccc(O)cc2)CC1
InChIKey: OLTJBWNNCOSOHB-WYMLVPIESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Agonist activity at full length ERalpha (unknown origin) after 24 hrs by ERE-driven luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 219.28, ALogP 3.27, HBA 3, HBD 2, PSA 52.82, QED 0.43
Compound (SMILES): O=C(Cc1ccc(F)cc1)Nc1cncc(-c2cc(-c3cccnc3)cs2)c1
InChIKey: GLCIBEGENZSGCS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human Dyrk1A expressed in Baculovirus expression system by Z'-LYTE assay
Measurement: IC50 = 14.3 nM (pChEMBL 7.840000152587891)
Descriptors: MW 389.46, ALogP 5.19, HBA 4, HBD 1, PSA 54.88, QED 0.51
Compound (SMILES): O=C1CCc2cc(CCCN3CCC(c4noc5cc(F)ccc45)CC3)cc3c2N1CCC3
InChIKey: CCFCUIZGGIRPTG-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 = 73.9 nM (pChEMBL 7.130000114440918)
Descriptors: MW 447.55, ALogP 5, HBA 4, HBD 0, PSA 49.58, QED 0.55
Compound (SMILES): Cc1c(C(=O)Nc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c(O)nn1C
InChIKey: YTIFSTOHDUXZPV-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of human IKKepsilon using ERLLDDRHDSGLDSMKDEE as substrate after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 367.25, ALogP 3.72, HBA 4, HBD 2, PSA 67.15, QED 0.8
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(S(N)(=O)=O)cc3)CC2)nc2ccn(COCc3ccccc3)c12
InChIKey: WTPLVPRRVXHPML-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 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 651.79, ALogP 5.61, HBA 10, HBD 2, PSA 148.39, QED 0.19
Compound (SMILES): Cc1cccc(-c2ccc3c(c2)nc(N)c2nc(CN4CCCC4=O)[nH]c23)c1
InChIKey: VQPCAOBWMBFDSL-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 (unknown origin) expressed in HEK-Blue cells
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 371.44, ALogP 3.79, HBA 4, HBD 2, PSA 87.9, QED 0.57
Compound (SMILES): Clc1ccccc1Cn1cnc(-c2cc(-c3cn[nH]n3)ccn2)c1Br
InChIKey: FBNBVIIMXLLIEO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 415.68, ALogP 4.19, HBA 5, HBD 1, PSA 72.28, QED 0.54
Compound (SMILES): CCCN1C(=O)C(=NNC(=O)c2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: RUDSFNURZISDCP-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 30.1 nM (pChEMBL 7.519999980926514)
Descriptors: MW 386.43, ALogP 1.22, HBA 5, HBD 2, PSA 121.93, QED 0.75
Compound (SMILES): C[C@@H](NC(=O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCc1ccccc1
InChIKey: LEFDHTPNDGQXKD-DTJMNSTISA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S immunoproteasome beta-1 using Ac-PAL-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 12500 nM (pChEMBL 4.900000095367432)
Descriptors: MW 749.87, ALogP 4.24, HBA 8, HBD 6, PSA 184.19, QED 0.1
Compound (SMILES): CCNC(=O)NCC1CCc2ccc3ccc(OC)cc3c21
InChIKey: JCPYDFOYATXTFR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-mesulergine from human 5-HT2C receptor expressed in CHO cell membranes after 60 mins by TopCount scintillation counting method
Measurement: Ki = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 298.39, ALogP 3.2, HBA 2, HBD 2, PSA 50.36, QED 0.91
Compound (SMILES): CC(=O)O[C@@H]1[C@@H]2C[C@H]([C@@H]1OC(C)=O)[C@H]1C(=O)N(CCCCN3CCN(c4cccc5sccc45)CC3)C(=O)[C@@H]21
InChIKey: FKVUODCCSPECOT-OUMHMPNFSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at 5-HT2A receptor (unknown origin) after 10 mins by calcium 5 dye based FLIPR assay
Measurement: IC50 = 546 nM (pChEMBL 6.260000228881836)
Descriptors: MW 553.68, ALogP 2.92, HBA 9, HBD 0, PSA 96.46, QED 0.28