lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN1CCC(c2ccc(Nc3ncc(F)c(-c4cc(F)c5c(c4)C(C)(CC)C(C)=N5)n3)nc2)CC1
InChIKey: KGVDWEZLAHTJSJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/ G1/S-specific cyclin-D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Kinase Inhibitory Activity Assay:     1.2.2 Preparation of kinase solution: Kinase solutions having the concentrations required for each reaction system were prepared from 100 ng/μl kinase stock solution and the 1× kinase reaction buffer.    1.2.3 Preparation of the test compound solution and control LY2835219 solution:      (1) Preparation of control LY2835219 solution        a. 1 μl of 10 mM standard substance stock solution was taken and added to 9 μl of kinase reaction buffer I and mixed well; then 90 μl of kinase reaction buffer I was added and mixed well; then 100 μl of kinase reaction buffer I was added and mixed well. The final concentration was 50 μM.        b. 40 μl of kinase reaction buffer II was added into B2 to B10 of a 96-well plate, and 50 μl of the above solution was added into B1;        c. 10 μl of solution was taken from well B1, added into B2, and mixed well; then 10 μl of the resulting solution was taken and added into B3, and dilution was carried out in sequence to B9, so as to obtain control solutions that are diluted by 5-fold sequentially.      (2) Preparation of test compound solution:        a. Test compound solutions at a certain concentration were taken, respectively, diluted with kinase reaction buffer I to a final concentration of 50 μM compound solution;        b. 40 μl of kinase reaction buffer II was added into H2 to H10 of the 96-well plate; and 50 μl of the above solution was added into H1;        c. 10 μl of solution was taken from well H1, added into H2, and mixed well; then 10 μl of the resulting solution was taken and added into H3, and dilution was carried out in sequence to H9, so as to obtain test compound solutions that are diluted by 5-fold sequentially.    1.2.4 Preparation of a mixed solution of reaction substrate and ATP:      a. Preparation of ATP solution:      200 μl of 0.1 mM ATP solution: 2 μl of 10 mM ATP was added to 198 μl of kinase reaction buffer I;      300 μl of 50 μM ATP solution: 150 μl of kinase reaction buffer I was added to 150 μl of the above 0.1 mM ATP solution;      b. Preparation of 300 μl of reaction substrate solution:      150 μl 1 μg/μl reaction substrate stock solution was added to 150 μl kinase reaction buffer I, and mixed well;      c. The above a/b solutions were mixed to obtain mixed solutions, respectively.
Measurement: IC50 = 10.9 nM (pChEMBL 7.960000038146973)
Descriptors: MW 490.6, ALogP 6.53, HBA 6, HBD 1, PSA 66.3, QED 0.43
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N(CC(=O)O)Cc1ccc(O)cc1)[C@@H](C)O)C(C)C
InChIKey: RDTCMFBCOBFOGW-IIQVFVSRSA-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 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 4050.51
Compound (SMILES): CCc1c(-c2ccccc2)c(-c2ccccc2)nn1-c1ccccc1-c1ccccc1OCC(=O)O
InChIKey: QOZQWDYXMBAUNZ-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of 1,8-ANS from FABP4 (unknown origin) after 3 mins by fluorescence assay
Measurement: IC50 = 2820 nM (pChEMBL 5.550000190734863)
Descriptors: MW 474.56, ALogP 6.9, HBA 4, HBD 1, PSA 64.35, QED 0.27
Compound (SMILES): Nc1oc2c(-c3ccncc3)nccc2c1Nc1cc(F)cc(F)c1
InChIKey: CIMJQNRQKRVJNM-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 338.32, ALogP 4.49, HBA 5, HBD 2, PSA 76.97, QED 0.58
Compound (SMILES): CCN(CC)CCCCCCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1
InChIKey: GGWONWDLXWAMAR-ZBJSNUHESA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 37800 nM (pChEMBL 4.420000076293945)
Descriptors: MW 407.55, ALogP 5.63, HBA 4, HBD 0, PSA 38.77, QED 0.36
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1cccc(Cl)c1
InChIKey: WHDIGPINEOYMPY-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 313.74, ALogP 3.5, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): COc1ccc(C(/C=C/CN2CCCC(C(=O)O)C2)(c2ccc(OC)cc2)c2ccsc2)cc1
InChIKey: HNJPWFZNUDBUJY-SYZQJQIISA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by liquid scintillation counting method
Measurement: IC50 = 7585.78 nM (pChEMBL 5.119999885559082)
Descriptors: MW 477.63, ALogP 5.45, HBA 5, HBD 1, PSA 59, QED 0.42
Compound (SMILES): Clc1ccc(Cn2cnc(-c3cc4[nH]nnc4cn3)c2)cc1Cl
InChIKey: JHUVNOIUTLYUSM-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 345.19, ALogP 3.57, HBA 5, HBD 1, PSA 72.28, QED 0.62
Compound (SMILES): Cc1cn(-c2ccc3n(c2=O)CCN(C[C@@]24C[C@@H]2C(C)(C)Oc2ccc(C(F)(F)F)cc24)C3=O)cn1
InChIKey: LHTSLMHEFKNOOX-PXDATVDWSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 498.51, ALogP 3.95, HBA 6, HBD 0, PSA 69.36, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)NN=C2C(=O)Nc3ccc(Cl)cc32)cc1
InChIKey: KYGSCLFHNXEJAW-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 = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 378.8, ALogP 1.07, HBA 5, HBD 3, PSA 130.72, QED 0.69
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CC4(C3)CC(F)(F)C4)nc(-c3cccc(C(F)(F)F)n3)n2)CC1
InChIKey: MBSONQUQQPPYRL-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 504.45, ALogP 5.93, HBA 6, HBD 2, PSA 75.62, QED 0.49
Compound (SMILES): Cc1[nH]nc(NC(=O)c2ccccn2)c1-c1ccc(Cl)c(Cl)c1
InChIKey: HBJKUJXDSAMGCN-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 347.21, ALogP 4.34, HBA 3, HBD 2, PSA 70.67, QED 0.74
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CCCCCNC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)CCC(=O)NCCCC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)O)[C@@H](C)O)[C@@H](C)CC)NC(=O)[C@H](CC(N)=O)NC1=O
InChIKey: ROSXYSDJZUJAFR-QCETVNLESA-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 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 2250.6
Compound (SMILES): Nc1cccc(-c2csc(NC(=O)CCCCCCC(=O)Nc3ccccc3N)n2)c1
InChIKey: CMFSOZAEQZHYJF-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 = 60.3 nM (pChEMBL 7.21999979019165)
Descriptors: MW 437.57, ALogP 4.89, HBA 6, HBD 4, PSA 123.13, QED 0.27
Compound (SMILES): C[C@@H](Nc1nc(Nc2ccnc(C3(C#N)CC3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: HJCRKYCQHOQKKS-LLVKDONJSA-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 494.4, ALogP 5.01, HBA 8, HBD 2, PSA 112.3, QED 0.46
Compound (SMILES): Cn1nccc1S(=O)(=O)N[C@@H]1C[C@H](NC#N)c2cc(-c3ncnc4[nH]ccc34)ccc21
InChIKey: CEVCDPUMVLQLEJ-DLBZAZTESA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human His-tagged TYK2 expressed in SF21/baculovirus expression system using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 434.49, ALogP 1.89, HBA 8, HBD 3, PSA 141.38, QED 0.32
Compound (SMILES): C=C(C)c1ccc2c(=O)c3cc(C(=O)O)c(N)nc3oc2c1
InChIKey: XQUAKFCOMISRTF-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of human IKKepsilon (1 to 655 residues) expressed in Baculovirus infected SF9 insect cells using myelin basic protein as substrate in presence of [gamma-33P]-ATP by radiometric kinase assay
Measurement: IC50 = 7244.36 nM (pChEMBL 5.139999866485596)
Descriptors: MW 296.28, ALogP 2.65, HBA 5, HBD 2, PSA 106.42, QED 0.7
Compound (SMILES): COCCN[C@H]1CC[C@H](Nc2cc(-c3csc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XSDZPPRQLIZLDG-IYARVYRRSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MV4-11 cells assessed as decrease in RNA polymerase 2 phosphorylation at Ser 2 residues in CTD domain after 2 hrs by immunoblotting analysis
Measurement: EC50 < 100 nM (pChEMBL 7)
Descriptors: MW 505.09, ALogP 4.55, HBA 9, HBD 3, PSA 104.12, QED 0.4
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3ccc(F)c(F)c3)CC2)cc(C(C)(C)C)c1O
InChIKey: PIAQBVLTUJMIOG-CSKARUKUSA-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 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 512.69, ALogP 6.7, HBA 3, HBD 2, PSA 52.57, QED 0.41
Compound (SMILES): CC1CC(C(=O)Nc2nc3ccc(Br)cc3s2)CC(C)(C)C1
InChIKey: WQYBWHRVRJWCOS-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 12700 nM (pChEMBL 4.900000095367432)
Descriptors: MW 381.34, ALogP 5.46, HBA 3, HBD 1, PSA 41.99, QED 0.75
Compound (SMILES): COc1cc2c(=O)n(C3CCCCCCC3)c3c4cc[nH]c4ncc3c2cc1OC
InChIKey: NBODSYUTGVDXCY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 2 hrs by filter-binding method
Measurement: IC50 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 405.5, ALogP 5.33, HBA 5, HBD 1, PSA 69.14, QED 0.47
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H]3C(=O)N(CC)C(=O)N23)s1
InChIKey: PYRZRKTWNHDCON-VQIMIIECSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of recombinant human N-terminal GST-tagged PDE3B (592 to end residues) expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 379.49, ALogP 4.09, HBA 3, HBD 1, PSA 56.41, QED 0.7
Compound (SMILES): CCOc1nc(Cl)ccc1C1(N2CCN(c3ccnc(C)c3)CC2)C(=O)N(S(=O)(=O)c2ccc(OC)cn2)c2ccc(C#N)cc21
InChIKey: ZLSVWMNWYLPEOW-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes in presence of NADPH and Luciferin BE 50
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 660.16, ALogP 3.91, HBA 11, HBD 0, PSA 141.85, QED 0.25
Compound (SMILES): O=C(O)C1=C[C@H](O)[C@@H](NC(=O)C2CCC2)[C@H]([C@H](O)[C@H](O)CO)O1
InChIKey: QRUHEHZWGDXEOE-RULNCXCMSA-N
Target: Sialidase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WWR8
Assay: Inhibition of MBP-fused human NEU4 expressed in Escherichia coli using 4MU-NANA as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 81000 nM (pChEMBL 4.090000152587891)
Descriptors: MW 331.32, ALogP -2.29, HBA 7, HBD 6, PSA 156.55, QED 0.32
Compound (SMILES): Cn1cc(C2CCN(C(=O)C3CCCCC3)CC2)c2cc(NC(=O)c3cc(C#N)ccn3)ccc21
InChIKey: LRJCIDHTWFKTMZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4-fused RORC2 LBD (unknown origin) expressed in mouse neuro2A cells assessed as inhibition of transcriptional activity after 20 to 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 469.59, ALogP 4.98, HBA 5, HBD 1, PSA 91.02, QED 0.58
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: MRPABPZGFWKLOQ-AUBJFONBSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 4022.46
Compound (SMILES): O=C(O)c1[nH]c2cc(Cl)ccc2c1C(C(=O)NC12CC3CC(CC(C3)C1)C2)N1C(=O)CC1c1ccc(OCc2ccccc2)cc1
InChIKey: LYHGAJYPJOIIHJ-UHFFFAOYSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Inhibition of 5'-FAM-LTFEHYWAQLTS binding to N-terminal domain of recombinant human MDMX after 15 mins by fluorescence polarization assay
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 638.16, ALogP 7.2, HBA 4, HBD 3, PSA 111.73, QED 0.17
Compound (SMILES): Oc1ccc(F)c(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: LBPUKFIAHANDDC-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 458.44, ALogP 4.76, HBA 7, HBD 3, PSA 95.85, QED 0.56
Compound (SMILES): Cc1ccc2sc(N)c(Nc3ccc(F)c(F)c3)c2c1
InChIKey: WHXICMYHONRMES-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 290.34, ALogP 4.81, HBA 3, HBD 2, PSA 38.05, QED 0.71
Compound (SMILES): NS(=O)(=O)c1ccc(O)c([N+](=O)[O-])c1
InChIKey: SXSOYEBKXCZKDH-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 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 218.19, ALogP -0.05, HBA 5, HBD 2, PSA 123.53, QED 0.53
Compound (SMILES): CC(C)COc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: UDNZKYWBVTTWJF-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 401.85, ALogP 4.23, HBA 6, HBD 1, PSA 86.47, QED 0.61
Compound (SMILES): CC(C)C(C)Nc1nc(NC(C)C(C)C)nc(-c2cccc(N)n2)n1
InChIKey: AZFYXQQKGDXNAX-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 343.48, ALogP 3.43, HBA 7, HBD 3, PSA 101.64, QED 0.71
Compound (SMILES): CCN(CC)CCCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1
InChIKey: QHFXDEZFKBQYBR-KNTRCKAVSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 62900 nM (pChEMBL 4.199999809265137)
Descriptors: MW 365.47, ALogP 4.46, HBA 4, HBD 0, PSA 38.77, QED 0.51
Compound (SMILES): Nc1oc2cnccc2c1Nc1ccc(F)c(OC(F)(F)F)c1
InChIKey: YCUJCSINODVYLT-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 327.24, ALogP 4.19, HBA 5, HBD 2, PSA 73.31, QED 0.71
Compound (SMILES): C#Cc1cccc(Nc2c(N)oc3cnccc23)c1
InChIKey: RLGKTZHAYVDANU-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 249.27, ALogP 3.13, HBA 4, HBD 2, PSA 64.08, QED 0.68
Compound (SMILES): c1ccc2c(c1)CCCC2Cn1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1
InChIKey: AHJAGGVQXVXBBG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 357.42, ALogP 3.25, HBA 6, HBD 1, PSA 85.17, QED 0.61
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C/c2ccc(N3CCN(c4ccccn4)CC3)cc2)cc1
InChIKey: OEUKEIPHPXCMQD-KOEQRZSOSA-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 = 235.3 nM (pChEMBL 6.630000114440918)
Descriptors: MW 436.54, ALogP 2.5, HBA 7, HBD 2, PSA 103.92, QED 0.45
Compound (SMILES): O=C(O)c1ccnc(-n2ccc(CCc3ccccc3)n2)c1
InChIKey: IKDUYJZLUXCOMP-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 293.33, ALogP 2.75, HBA 4, HBD 1, PSA 68.01, QED 0.79
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCNCC3CC(F)(F)C3)cn2)c1
InChIKey: QVDRDNVABMUEIS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 336.34, ALogP 2.28, HBA 5, HBD 2, PSA 80.04, QED 0.76
Compound (SMILES): CC(C)(Cn1cnc(-c2cc(C(=O)O)ccn2)c1)c1ccccc1Cl
InChIKey: WJNMKYLJNLYALB-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 355.83, ALogP 4.27, HBA 4, HBD 1, PSA 68.01, QED 0.74
Compound (SMILES): CC(C)(C)Nc1nc(Nc2cc(F)cc(C#N)c2)nc(-c2nccc(C(F)(F)F)n2)n1
InChIKey: TWTMGQUEQUWIKR-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 6 hrs before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 432.39, ALogP 4.31, HBA 8, HBD 2, PSA 112.3, QED 0.59
Compound (SMILES): N#CC1(c2cc(Nc3nc(N[C@@H]4CCC(F)(F)C4)nc(-c4cccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: FQOVWGJWJAOWBO-CQSZACIVSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 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 502.45, ALogP 5.25, HBA 8, HBD 2, PSA 112.3, QED 0.44
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-c2cncc3[nH]ccc23)n1
InChIKey: RIAAGYPMCVIWMN-CYBMUJFWSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using midazolam as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of NADPH by LC-MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 413.5, ALogP 2.28, HBA 7, HBD 1, PSA 101.07, QED 0.7
Compound (SMILES): Clc1ccc(Cn2cnc(-c3cc(-c4nn[nH]n4)ccn3)c2)cc1
InChIKey: BDSGDBHMKQRXML-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 337.77, ALogP 2.83, HBA 6, HBD 1, PSA 85.17, QED 0.62
Compound (SMILES): CS(=O)(=O)Nc1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)C4CCOCC4)CC3)n2c1
InChIKey: LJWLONBDFLEPIK-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 566.51, ALogP 3.75, HBA 7, HBD 1, PSA 96.25, QED 0.49
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1ccc(CP(=O)(O)O)cc1)C(=O)N1CCC[C@@H]1C(=O)NC1Cc2ccccc2C1
InChIKey: JIDWKTJXOGCVKX-RIEVBORMSA-N
Target: Baculoviral IAP repeat-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13489
Assay: Displacement of AVPIAQKSEK-biotin from cIAP2 BIR3 (unknown origin) after 1 hr by DELFIA
Measurement: IC50 = 1103 nM (pChEMBL 5.960000038146973)
Descriptors: MW 556.6, ALogP 1.27, HBA 5, HBD 5, PSA 148.07, QED 0.28
Compound (SMILES): Cn1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: JMBGPAGLZBKRJX-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: PHF8 Assay: The ability of test compounds to inhibit the activity of PHF8 was determined in 384-well plate format under the following reaction conditions: 3 nM PHF8, 200 nM H3K9me1-biotin labeled peptide (Anaspec cat #64358), 0.5 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified-histone H3 lysine 9/lysine27 (H3K9/K27) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 0.5 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 600 nM H3K9me1-biotin labeled peptide and 1.5 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 9 nM PHF8 to initiate the reaction. The reaction mixture was incubated at rt for 15 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 1 nM Europium-anti-unmodified H3K9/K27 antibody. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 226.24, ALogP 1.27, HBA 5, HBD 1, PSA 72.28, QED 0.71
Compound (SMILES): O=C(c1cccc(F)c1)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3ccc(-c4ccccc4)cn23)CC1
InChIKey: HELIDGLLRBYAMT-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 525.03, ALogP 6.42, HBA 4, HBD 0, PSA 40.85, QED 0.27
Compound (SMILES): CC(C)(C)c1ccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: OTANKDWZNIFZRG-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 440.47, ALogP 5.29, HBA 5, HBD 1, PSA 72.28, QED 0.46
Compound (SMILES): N#Cc1cc(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: DWYLFGVHVCAESV-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 476.41, ALogP 4.95, HBA 8, HBD 2, PSA 112.3, QED 0.5
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1ccc(S(=O)(=O)F)cc1)C(=O)N1CCC[C@@H]1c1cncc(Cc2cccc(F)c2)n1
InChIKey: OJNVAHCYXGMTQI-LGIRGXTLSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from XIAP BIR3 Lys311E mutant (unknown origin) after 1 hr by DELFIA
Measurement: IC50 = 1039 nM (pChEMBL 5.980000019073486)
Descriptors: MW 614.68, ALogP 2.05, HBA 8, HBD 3, PSA 150.46, QED 0.28
Compound (SMILES): FC1(F)CCC(Nc2nc(Nc3ccnc(C(F)(F)F)c3)nc(-c3cccc(Cl)n3)n2)C1
InChIKey: GCDKECOSGNFZAP-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 471.82, ALogP 5.34, HBA 7, HBD 2, PSA 88.51, QED 0.38
Compound (SMILES): O=c1cc(Nc2ccc(-c3ccccc3)cc2)[nH]c(=O)n1O
InChIKey: PCGFBWBCNOYCDT-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of RNase H activity of full length recombinant HIV1 reverse transcriptase assessed as reduction in RNA 5'-end directed cleavage using HTS3 substrate
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 295.3, ALogP 2.18, HBA 5, HBD 3, PSA 87.12, QED 0.65
Compound (SMILES): O=C(O)c1ccc2c(C(=O)c3ccccc3)cc(C(=O)c3ccccc3)c-2cc1
InChIKey: ZWHRVBXXCAZNDE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using mephenytoin as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 380.4, ALogP 4.95, HBA 3, HBD 1, PSA 71.44, QED 0.5
Compound (SMILES): CS(=O)(=O)Nc1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(O)CC3)n2c1
InChIKey: JIKOIWDLRZSTDC-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 470.38, ALogP 3.19, HBA 7, HBD 2, PSA 90.18, QED 0.6
Compound (SMILES): NC(=O)c1cnc2c(NC3CC3)cc(Nc3cccc(-c4ccc(C(F)(F)F)cc4F)c3)nn12
InChIKey: WBDSWBZUQSEKIW-UHFFFAOYSA-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 470.43, ALogP 4.97, HBA 6, HBD 3, PSA 97.34, QED 0.35
Compound (SMILES): O=C(O)CC1COc2cc(OCCCOc3ccc(-c4ccccc4)cc3)ccc21
InChIKey: AQCAZJIZBLVBHO-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 expressed in CHO cells assessed as increase in intracellular Ca2+ flux after 1 hr by Fluo4-AM dye based FLIPR assay
Measurement: EC50 = 4260 nM (pChEMBL 5.369999885559082)
Descriptors: MW 404.46, ALogP 5.15, HBA 4, HBD 1, PSA 64.99, QED 0.5
Compound (SMILES): Clc1ccccc1Cn1cnc(-c2cc3[nH]nnc3cn2)c1
InChIKey: NZRMHFYQBPOOHK-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 310.75, ALogP 2.92, HBA 5, HBD 1, PSA 72.28, QED 0.63
Compound (SMILES): C=CC(=O)N[C@H]1CCN(c2ccc(C(N)=O)c(Nc3ccc(N4C[C@@H](C)O[C@@H](C)C4)cc3)n2)C1
InChIKey: YQBSMRRMOZCNRZ-SCTDSRPQSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human WBC
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 464.57, ALogP 2.42, HBA 7, HBD 3, PSA 112.82, QED 0.54
Compound (SMILES): CN(C)c1ccc2oc3nc(N)c(-c4nn[nH]n4)cc3c(=O)c2c1
InChIKey: ZVBIBRJWIINCLT-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: Q14164
Assay: Inhibition of human IKKepsilon (1 to 655 residues) expressed in Baculovirus infected SF9 insect cells using myelin basic protein as substrate in presence of [gamma-33P]-ATP by radiometric kinase assay
Measurement: IC50 = 575.44 nM (pChEMBL 6.239999771118164)
Descriptors: MW 323.32, ALogP 1.17, HBA 8, HBD 2, PSA 126.82, QED 0.53
Compound (SMILES): O=C(Nc1ccc(Sc2nc3ccccc3s2)cc1)c1cccc(Br)c1O
InChIKey: IXVZWQZFLVNMBK-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 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 457.37, ALogP 6.17, HBA 5, HBD 2, PSA 62.22, QED 0.38
Compound (SMILES): CN1Cc2c(Cl)cc(Cl)cc2[C@@H](c2ccc(S(=O)(=O)NCCOCCOCCNC(=O)NCCCCNC(=O)NCCOCCOCCNS(=O)(=O)c3cccc([C@@H]4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)cc2)C1.Cl.Cl
InChIKey: HJOARWJYLHFTDH-DFIDSBDCSA-N
Target: Sodium/hydrogen exchanger 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P48764
Assay: Inhibition of human NHE3 expressed in OK cells assessed as reduction in Na+ dependent H+ antiport co-treated with NaCl-HEPES buffer for 60 mins followed by compound washout and subsequent incubation for 30 mins in presence of NaCl-HEPES buffer by BCECF-AM dye based fluorescence assay
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 1145.07
Compound (SMILES): CC(C)(O)CNc1nc(NC2CCC(F)(F)CC2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: IWJRYKAPBRKGLL-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 >= 1000 nM (pChEMBL 6)
Descriptors: MW 446.42, ALogP 4.13, HBA 7, HBD 3, PSA 95.85, QED 0.57
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-AWEZNQCLSA-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 = 644 nM (pChEMBL 6.190000057220459)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): COc1nc(N2CC(O)C2)ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1
InChIKey: IZJBUCRZPWJSLP-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of human N-terminal GST-tagged ROS cytoplasmic domain (1883 to 2347 residues) expressed in baculovirus expression system after 1 hr by mobility shift assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 491.96, ALogP 2.57, HBA 10, HBD 4, PSA 141.6, QED 0.37
Compound (SMILES): C[C@@H](Nc1nc(Nc2ccnc(-c3ccccc3)c2)nc(-c2cccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: NWTISIXHXPIMSM-CYBMUJFWSA-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 505.43, ALogP 6.12, HBA 7, HBD 2, PSA 88.51, QED 0.31