lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(Cn1cnc(-c2cc(C(=O)O)ccn2)c1)c1ccccc1Cl
InChIKey: WJNMKYLJNLYALB-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 355.83, ALogP 4.27, HBA 4, HBD 1, PSA 68.01, QED 0.74
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-c2cncc3[nH]ccc23)n1
InChIKey: RIAAGYPMCVIWMN-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR in human MDA-MB-468 cells assessed as decrease in AKT phosphorylation at S473 residue
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 413.5, ALogP 2.28, HBA 7, HBD 1, PSA 101.07, QED 0.7
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-AWEZNQCLSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of BMX (unknown origin) in presence of 1 mM ATP concentration
Measurement: IC50 = 6310 nM (pChEMBL 5.199999809265137)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: SSJGXNSABQPEKM-SBUIBGKBSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O70342
Assay: Displacement of [125I]-PYY(1 to 36 residues) from mouse Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: EC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 4310.81
Compound (SMILES): O=C(O)c1ccnc(-c2cn(Cc3ccccc3F)cn2)c1
InChIKey: FWSGIYDMJPQQGL-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 297.29, ALogP 2.83, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): CC(C)(O)CNc1nc(Nc2cc(F)cc(C#N)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: MVCBBRZTMZDXPK-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: In Vitro Assays for IDH2m R140Q Inhibitors: Compounds are assayed for IDH2 R140Q inhibitory activity through a cofactor depletion assay. Compounds are preincubated with enzyme and cofactor, then the reaction is started by the addition of α-KG, and allowed to proceed for 60 minutes under conditions previously demonstrated to be linear. The reaction is terminated by the addition of a second enzyme, diaphorase, and a corresponding substrate, resazurin. Diaphorase reduces resazurin to the highly fluorescent resorufin with the concomitant oxidation of NADPH to NADP, both halting the IDH2 reaction by depleting the available cofactor pool and facilitating quantitation of the amount of cofactor remaining after a specific time period through quantitative production of an easily detected fluorophore.Specifically, into each of 12 wells of a 384-well plate, 1 μl of 50× compound dilution series is placed, followed by the addition of 40 μl of buffer (50 mM potassium phosphate (K2HPO4), pH 7.5; 150 mM NaCl; 10 mM MgCl2, 10% glycerol, 0.05% bovine serum albumin, 2 mM beta-mercaptoethanol) containing 0.39 μg/ml IDH2 R140Q protein, 5 uM NADPH and 750 uM NADP. The test compound is then incubated for 16 hrs at room temperature with the enzyme and cofactors before starting the IDH2 reaction with the addition of 10 μl of substrate mix containing 8 mM α-KG (final concentration 1.6 mM) in the buffer described above. After a further 1 hour of incubation at room temperature, the reaction is halted and the remaining NADPH measured through conversion of resazurin to resorufin by the addition of 25 μl Stop Mix (36 μg/ml diaphorase enzyme and 60 μM resazurin; in buffer). After one minute of incubation the plate is read on a plate reader at Ex544/Em590.
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 447.4, ALogP 3.89, HBA 8, HBD 3, PSA 119.64, QED 0.49
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@]1(C)CCC/C=C\CCC[C@](C)(NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@]2(C)CCC/C=C\CCC[C@](C)(NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(C)=O)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N2)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(N)=O
InChIKey: RLKTUAAXFPWYKS-MXKUBBDVSA-N
Target: Envelope glycoprotein gp160 (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q6QLK5
Assay: Inhibition of gp41 V38A/N42T double 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 = 0.84 nM (pChEMBL 9.079999923706055)
Descriptors: MW 3112.73
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@H]3C(=O)N(CC)C(=O)N23)o1
InChIKey: VKKJMPZSQBNIOL-QFBILLFUSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of recombinant human N-terminal GST-tagged PDE10A1 (2 to 789 residues) expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 363.42, ALogP 3.62, HBA 3, HBD 1, PSA 69.55, QED 0.72
Compound (SMILES): CCn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(OC(F)(F)F)c2)c2c(N)ncnc21
InChIKey: APPXQUDJLJXULP-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Inhibition of recombinant human Tie2 Q939H/Q940H double mutant (771 to end residues) using poly(Glu, Tyr) 4:1 as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 481.48, ALogP 4.73, HBA 6, HBD 1, PSA 86.27, QED 0.45
Compound (SMILES): CNC(=S)NCC1CCc2ccc3ccc(OC)cc3c21
InChIKey: BFMFHHBVYCVTTH-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 300.43, ALogP 2.97, HBA 2, HBD 2, PSA 33.29, QED 0.85
Compound (SMILES): CC(O)CNc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: YADRVMCMMMHOSZ-QVDQXJPCSA-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-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 382.39, ALogP 2.96, HBA 7, HBD 3, PSA 95.85, QED 0.68
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)CC(=O)N(c2ccc(C(=O)O)cc2)C3)cc(OCC)c1-c1ccc(F)cc1.O=C(O)C(F)(F)F
InChIKey: VFUWYNPQDXMVOJ-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Displacement of (3-125I-Tyr11)-SRIF-28 from mouse SSTR5 expressed in CHO-K1 cell membranes by filtration binding assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 546.64, ALogP 6.01, HBA 5, HBD 1, PSA 79.31, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)c1ccccc1N)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: KOFSEBGXKJTRQA-DVERMALCSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y2R expressed in CHO cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 1737.99
Compound (SMILES): CNC(=O)Nc1ccc2c(c1)CC[C@@]21OC(=O)N(CC(=O)N(Cc2ccc(F)cc2)[C@@H](C)C(F)(F)F)C1=O
InChIKey: VRVJKILQRBSEAG-LFPIHBKWSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: GPCRScan assay: inhibition of SERT
Measurement: Ki = 223.27 nM (pChEMBL 6.650000095367432)
Descriptors: MW 536.48, ALogP 3.68, HBA 5, HBD 2, PSA 108.05, QED 0.55
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCc3ccccc3Cl)cn2)c1
InChIKey: NZRXUQUWPPLOHA-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 327.77, ALogP 3.54, HBA 4, HBD 1, PSA 68.01, QED 0.78
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2CC(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChIKey: PWXAIRIXMQTTSE-DCFHFQCYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132L mutant (unknown origin)
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 597, ALogP 4.71, HBA 6, HBD 1, PSA 119.29, QED 0.4
Compound (SMILES): O=C(O)c1ccnc(-c2cn(Cc3ccc(F)cc3)cn2)c1
InChIKey: TYQVGBHPIVDCJP-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 297.29, ALogP 2.83, HBA 4, HBD 1, PSA 68.01, QED 0.8
Compound (SMILES): OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCN(CCCCCc2ccc(F)cc2)CC1
InChIKey: UBNDBTRGSCEYOS-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H]Pyrilamine from human H1 receptor expressed in HEK cells by radioligand binding assay
Measurement: Ki = 718 nM (pChEMBL 6.139999866485596)
Descriptors: MW 443.91, ALogP 6.19, HBA 2, HBD 1, PSA 23.47, QED 0.41
Compound (SMILES): COc1c(-c2ccccc2)oc2c(ccc3ccoc32)c1=O
InChIKey: JANBLZHPNGBWAO-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of recombinant human CYP1A1 expressed in baker's yeast-derived microsomes (Sacchrosomes) using 7-ethoxyresorufin substrate by EROD assay relative to control
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 292.29, ALogP 4.21, HBA 4, HBD 0, PSA 52.58, QED 0.55
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 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 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 2250.6
Compound (SMILES): COCCN[C@H]1CC[C@H](Nc2cc(-c3csc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XSDZPPRQLIZLDG-IYARVYRRSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant full length His-tagged human CDK9/CyclinT1 expressed in baculovirus expression system
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 505.09, ALogP 4.55, HBA 9, HBD 3, PSA 104.12, QED 0.4
Compound (SMILES): CC(C)COc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: UDNZKYWBVTTWJF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Activity 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 401.85, ALogP 4.23, HBA 6, HBD 1, PSA 86.47, QED 0.61
Compound (SMILES): O=C(O)c1ccnc(-n2ccc(CCc3ccccc3)n2)c1
InChIKey: IKDUYJZLUXCOMP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Activity 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 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 293.33, ALogP 2.75, HBA 4, HBD 1, PSA 68.01, QED 0.79
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-c2cncc3[nH]ccc23)n1
InChIKey: RIAAGYPMCVIWMN-CYBMUJFWSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR in human MDA-MB-468 cells assessed as decrease in 70S6K S235/236 phosphorylation
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 413.5, ALogP 2.28, HBA 7, HBD 1, PSA 101.07, QED 0.7
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-AWEZNQCLSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of BLK (unknown origin) in presence of 1 mM ATP concentration
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: SSJGXNSABQPEKM-SBUIBGKBSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y1R expressed in BHK-21 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 0.1259 nM (pChEMBL 9.899999618530273)
Descriptors: MW 4310.81
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@H]3C(=O)N(CC)C(=O)N23)o1
InChIKey: VKKJMPZSQBNIOL-QFBILLFUSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE11A4 expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 363.42, ALogP 3.62, HBA 3, HBD 1, PSA 69.55, QED 0.72
Compound (SMILES): CCn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(OC(F)(F)F)c2)c2c(N)ncnc21
InChIKey: APPXQUDJLJXULP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: O15264
Assay: Inhibition of recombinant full length human SAPK4 using myelin basic protein as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis
Measurement: IC50 = 347 nM (pChEMBL 6.460000038146973)
Descriptors: MW 481.48, ALogP 4.73, HBA 6, HBD 1, PSA 86.27, QED 0.45
Compound (SMILES): CNC(=S)NCC1CCc2ccc3ccc(OC)cc3c21
InChIKey: BFMFHHBVYCVTTH-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 300.43, ALogP 2.97, HBA 2, HBD 2, PSA 33.29, QED 0.85
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)CC(=O)N(c2ccc(C(=O)O)cc2)C3)cc(OCC)c1-c1ccc(F)cc1.O=C(O)C(F)(F)F
InChIKey: VFUWYNPQDXMVOJ-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 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 546.64, ALogP 6.01, HBA 5, HBD 1, PSA 79.31, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)c1ccccc1N)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: KOFSEBGXKJTRQA-DVERMALCSA-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 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 1737.99
Compound (SMILES): CNC(=O)Nc1ccc2c(c1)CC[C@@]21OC(=O)N(CC(=O)N(Cc2ccc(F)cc2)[C@@H](C)C(F)(F)F)C1=O
InChIKey: VRVJKILQRBSEAG-LFPIHBKWSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: GPCRScan assay: inhibition of SERT
Measurement: Ki = 218.78 nM (pChEMBL 6.659999847412109)
Descriptors: MW 536.48, ALogP 3.68, HBA 5, HBD 2, PSA 108.05, QED 0.55
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2CC(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChIKey: PWXAIRIXMQTTSE-DCFHFQCYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132G mutant (unknown origin)
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 597, ALogP 4.71, HBA 6, HBD 1, PSA 119.29, QED 0.4
Compound (SMILES): OC1(c2ccc(Cl)c(C(F)(F)F)c2)CCN(CCCCCc2ccc(F)cc2)CC1
InChIKey: UBNDBTRGSCEYOS-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]Cimetidine from human H2 receptor expressed in HEK cells by radioligand binding assay
Measurement: Ki = 401 nM (pChEMBL 6.400000095367432)
Descriptors: MW 443.91, ALogP 6.19, HBA 2, HBD 1, PSA 23.47, QED 0.41
Compound (SMILES): COc1c(-c2ccccc2)oc2c(ccc3ccoc32)c1=O
InChIKey: JANBLZHPNGBWAO-UHFFFAOYSA-N
Target: Cytochrome P450 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04798
Assay: Inhibition of human recombinant CYP1A1 expressed in adherent HEK293 cells assessed as protection of cells against CYP1A1-mediated sensitivity to to B[a]P-induced cytotoxicity by measuring B[a]P- EC50 by MTT assay (Rvb = 0.8 +/- 0.1 uM)
Measurement: EC50 = 13500 nM (pChEMBL 4.869999885559082)
Descriptors: MW 292.29, ALogP 4.21, HBA 4, HBD 0, PSA 52.58, QED 0.55
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 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 2250.6
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 11B (SINGLE PROTEIN), Homo sapiens
UniProt: P21127
Assay: Inhibition of recombinant GST-tagged inactive state of human CDK11
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 505.09, ALogP 4.55, HBA 9, HBD 3, PSA 104.12, QED 0.4
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: Activity Assay: The ability of test compounds to inhibit the activity of JMJD2A was determined in 384-well plate format under the following reaction conditions: 2 nM JMJD2A, 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 plate, followed by the addition of 2 μl of 6 nM JMJD2A 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 401.85, ALogP 4.23, HBA 6, HBD 1, PSA 86.47, QED 0.61
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: Activity Assay: The ability of test compounds to inhibit the activity of JMJD2A was determined in 384-well plate format under the following reaction conditions: 2 nM JMJD2A, 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 plate, followed by the addition of 2 μl of 6 nM JMJD2A 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 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 293.33, ALogP 2.75, HBA 4, HBD 1, PSA 68.01, QED 0.79
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-c2cncc3[nH]ccc23)n1
InChIKey: RIAAGYPMCVIWMN-CYBMUJFWSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha in human BT-474 cells assessed as decrease in AKT phosphorylation at T308 residue
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 413.5, ALogP 2.28, HBA 7, HBD 1, PSA 101.07, QED 0.7
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-AWEZNQCLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) in presence of 1 mM ATP concentration
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: SSJGXNSABQPEKM-SBUIBGKBSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y2R expressed in CHO cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 0.2512 nM (pChEMBL 9.600000381469727)
Descriptors: MW 4310.81
Compound (SMILES): CCc1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@H]3C(=O)N(CC)C(=O)N23)o1
InChIKey: VKKJMPZSQBNIOL-QFBILLFUSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: O54735
Assay: Inhibition of PDE5 in Wistar rat mesentric arteries assessed as inhibition of phenylephrine-induced contraction by measuring increase in acetylcholine-induced vasorelaxation by pressure myographic method
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 363.42, ALogP 3.62, HBA 3, HBD 1, PSA 69.55, QED 0.72
Compound (SMILES): CCn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(OC(F)(F)F)c2)c2c(N)ncnc21
InChIKey: APPXQUDJLJXULP-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant human Ret (658 to ed residues) using KKKSPGEYVNIEF as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 481.48, ALogP 4.73, HBA 6, HBD 1, PSA 86.27, QED 0.45
Compound (SMILES): CNC(=S)NCC1CCc2ccc3ccc(OC)cc3c21
InChIKey: BFMFHHBVYCVTTH-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Agonist activity at human MT2 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 300.43, ALogP 2.97, HBA 2, HBD 2, PSA 33.29, QED 0.85
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)CC(=O)N(c2ccc(C(=O)O)cc2)C3)cc(OCC)c1-c1ccc(F)cc1.O=C(O)C(F)(F)F
InChIKey: VFUWYNPQDXMVOJ-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse 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 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 546.64, ALogP 6.01, HBA 5, HBD 1, PSA 79.31, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)c1ccccc1N)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: KOFSEBGXKJTRQA-DVERMALCSA-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 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 1737.99
Compound (SMILES): CNC(=O)Nc1ccc2c(c1)CC[C@@]21OC(=O)N(CC(=O)N(Cc2ccc(F)cc2)[C@@H](C)C(F)(F)F)C1=O
InChIKey: VRVJKILQRBSEAG-LFPIHBKWSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Binding affinity to recombinant human p300 HAT domain expressed in Escherichia coli BL21-CodonPlus(DE3)-RIL cells assessed as dissociation constant using CMLVELHTQSQDRF as substrate by surface plasmon resonance analysis
Measurement: Kd = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 536.48, ALogP 3.68, HBA 5, HBD 2, PSA 108.05, QED 0.55
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2CC(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChIKey: PWXAIRIXMQTTSE-DCFHFQCYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in conversion of alpha-KG to D2-HG after 60 mins in presence of NADPH by diaphorase/resazurin coupled fluorescence assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 597, ALogP 4.71, HBA 6, HBD 1, PSA 119.29, QED 0.4
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 14/Cyclin-Y (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8ND76
Assay: Inhibition of recombinant GST-tagged human full length CDK14/cyclin Y (2 to end residues)
Measurement: IC50 = 1680 nM (pChEMBL 5.78000020980835)
Descriptors: MW 505.09, ALogP 4.55, HBA 9, HBD 3, PSA 104.12, QED 0.4
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-c2cncc3[nH]ccc23)n1
InChIKey: RIAAGYPMCVIWMN-CYBMUJFWSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of ATM phosphorylation at Ser1981 residue in human HT-29 cells using ionizing radiation
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 413.5, ALogP 2.28, HBA 7, HBD 1, PSA 101.07, QED 0.7
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-AWEZNQCLSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) in presence of 1 mM ATP concentration
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)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[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: SSJGXNSABQPEKM-SBUIBGKBSA-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 = 0.7943 nM (pChEMBL 9.100000381469727)
Descriptors: MW 4310.81
Compound (SMILES): CCn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(OC(F)(F)F)c2)c2c(N)ncnc21
InChIKey: APPXQUDJLJXULP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02779
Assay: Inhibition of recombinant human MLK2 (1 to 449 residues) using myelin basic protein as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 481.48, ALogP 4.73, HBA 6, HBD 1, PSA 86.27, QED 0.45
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)CC(=O)N(c2ccc(C(=O)O)cc2)C3)cc(OCC)c1-c1ccc(F)cc1.O=C(O)C(F)(F)F
InChIKey: VFUWYNPQDXMVOJ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of MK-499 binding to human ERG
Measurement: IC50 = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 546.64, ALogP 6.01, HBA 5, HBD 1, PSA 79.31, QED 0.35
Compound (SMILES): CNC(=O)Nc1ccc2c(c1)CC[C@@]21OC(=O)N(CC(=O)N(Cc2ccc(F)cc2)[C@@H](C)C(F)(F)F)C1=O
InChIKey: VRVJKILQRBSEAG-LFPIHBKWSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of N-terminal 6His-Flag tagged p300-BHC domain (1036 to 1822 residues) (unknown origin) expressed in Sf9 cells using the Bac-to-Bac baculovirus system using biotinylated synthetic Histone-H4 peptide incubated for 30 mins followed by substrate addition and measured after 1hr by TR-FRET assay
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 536.48, ALogP 3.68, HBA 5, HBD 2, PSA 108.05, QED 0.55
Compound (SMILES): N#Cc1ccnc(N2C(=O)CC[C@H]2CC(=O)N(c2cncc(F)c2)[C@H](C(=O)NC2CC(F)(F)C2)c2ccccc2Cl)c1
InChIKey: PWXAIRIXMQTTSE-DCFHFQCYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant (unknown origin) assessed as reduction in conversion of alpha-KG to D2-HG after 60 mins in presence of NADPH by diaphorase/resazurin coupled fluorescence assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 597, ALogP 4.71, HBA 6, HBD 1, PSA 119.29, QED 0.4
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 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Activation of human Y2R expressed in HEK293 cells assessed as inhibition of isoproterenol-induced increase in intracellular cAMP levels by calcium 5 dye-based FLIPR assay
Measurement: EC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 2250.6
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-Y/Cyclin-dependent kinase 16 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8ND76
Assay: Inhibition of recombinant GST-tagged inactive state of human CDK16 (108 to end residues)/cyclin Y (2 to end residues)
Measurement: IC50 = 292 nM (pChEMBL 6.539999961853027)
Descriptors: MW 505.09, ALogP 4.55, HBA 9, HBD 3, PSA 104.12, QED 0.4
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2(S(C)(=O)=O)CC2)nc(-c2cncc3[nH]ccc23)n1
InChIKey: RIAAGYPMCVIWMN-CYBMUJFWSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK phosphorylation at Ser2056 residue in human HT-29 cells using ionizing radiation
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 413.5, ALogP 2.28, HBA 7, HBD 1, PSA 101.07, QED 0.7
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]ccc34)cc21
InChIKey: RBDSMNWWGHWDMP-AWEZNQCLSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of HER2 (unknown origin) in presence of 1 mM ATP concentration
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 275.31, ALogP 2.68, HBA 4, HBD 2, PSA 77.39, QED 0.56