lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)N1CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(C(F)(F)F)n3)n2)CC1
InChIKey: PVZIUYNREPTYEJ-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 499.49, ALogP 4.37, HBA 7, HBD 2, PSA 95.93, QED 0.59
Compound (SMILES): COCC(=O)NCC1CCc2ccc3ccc(OC)cc3c21
InChIKey: QCENXOASTJWJCD-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 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 299.37, ALogP 2.64, HBA 3, HBD 1, PSA 47.56, QED 0.92
Compound (SMILES): N#CN[C@H]1CCc2ccc(-c3ncnc4[nH]cc(-c5cccc(CO)c5)c34)cc21
InChIKey: INXMROPBPUKGSQ-FQEVSTJZSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 > 9925 nM (pChEMBL 5.002999782562256)
Descriptors: MW 381.44, ALogP 3.84, HBA 5, HBD 3, PSA 97.62, QED 0.37
Compound (SMILES): O=C(O)c1ccnc(-c2cn(CCN3CCCc4cc(F)ccc43)cn2)c1
InChIKey: HFKOFUFQGTVMPB-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 366.4, ALogP 3.24, HBA 5, HBD 1, PSA 71.25, QED 0.75
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCC2CC(F)(F)C2)c1
InChIKey: RPTWQPJAAAJOAS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 309.27, ALogP 2.39, HBA 5, HBD 1, PSA 77.24, QED 0.92
Compound (SMILES): CCN1C(=O)[C@@H]2Cc3c([nH]c4ccccc34)[C@@H](c3ccc(C)o3)N2C1=O
InChIKey: QFMUYNLRTWIZJM-MAUKXSAKSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of full length recombinant human N-terminal GST-tagged PDE4A1A expressed in baculovirus infected sf9 cells using FAM-cyclic-3',5-AMP as substrate after 1 hr by fluorescence polarization assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 349.39, ALogP 3.37, HBA 3, HBD 1, PSA 69.55, QED 0.72
Compound (SMILES): COc1cccc2c1C(Cn1cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c1)CCC2
InChIKey: GXHWXOVAFMKAQV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, ALPHASCREEN Streptavidin-coated Donor beads, and ALPHASCREEN Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at rt for 40 min, followed by addition of 3 μl of 50 μg/ml ALPHASCREEN Streptavidin-coated Donor beads and ALPHASCREEN Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 454.46, ALogP 4.88, HBA 6, HBD 1, PSA 81.51, QED 0.47
Compound (SMILES): FC1(F)CC(Nc2nc(NC3CC(F)(F)C3)nc(-c3csc(C(F)(F)F)n3)n2)C1
InChIKey: PFVOIDGYPOBGID-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 442.36, ALogP 4.43, HBA 7, HBD 2, PSA 75.62, QED 0.67
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(Cl)cc2OCC(F)(F)F)c1
InChIKey: IVOFHPAJLLZMRL-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 427.77, ALogP 4.14, HBA 6, HBD 1, PSA 86.47, QED 0.61
Compound (SMILES): CCC(C)Oc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: DRXNXOKZAZEGFK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 401.85, ALogP 4.38, HBA 6, HBD 1, PSA 86.47, QED 0.6
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCOCC3)nc(-c3cccc(C(F)(F)F)n3)n2)CC1
InChIKey: XOGJBAWBFBEDJT-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 458.44, ALogP 4.53, HBA 7, HBD 2, PSA 84.85, QED 0.64
Compound (SMILES): Nc1ccc2oc(C(=O)NCCC3CCN(Cc4ccccc4)CC3)cc(=O)c2c1
InChIKey: IWMNPLRLJRDNCG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using p-tyramine as substrate pretreated for 15 mins followed by substrate addition by horse-radish peroxidase/amplex red-based fluorescence method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 405.5, ALogP 3.41, HBA 5, HBD 2, PSA 88.57, QED 0.61
Compound (SMILES): COc1ccc([Se]Cc2cnc(-c3ccc(S(N)(=O)=O)cc3)[se]2)cc1
InChIKey: SRFGQMGPNUZNDU-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of recombinant human carbonic anhydrase 5b incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki = 319.1 nM (pChEMBL 6.5)
Descriptors: MW 486.31
Compound (SMILES): O=C(O)c1ccnc(-n2nc(Cc3ccccc3Cl)cc2O)c1
InChIKey: AAHAWHWZDBQHHR-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 m/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 329.74, ALogP 2.92, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): CC[C@@H](Nc1nc(N[C@H](CC)C(F)(F)F)nc(-c2cccc(Cl)n2)n1)C(F)(F)F
InChIKey: SDUBFPITPDQUSW-NXEZZACHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 442.8, ALogP 5.09, HBA 6, HBD 2, PSA 75.62, QED 0.46
Compound (SMILES): CCc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)c(F)c1
InChIKey: VESNHHASMCDWDO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 341.34, ALogP 3.25, HBA 5, HBD 1, PSA 77.24, QED 0.74
Compound (SMILES): Oc1ccc(-c2cnc3[nH]cc(-c4ccc(F)cc4)c3c2)cc1O
InChIKey: IRJDHVRCNAUAOH-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 1993 nM (pChEMBL 5.699999809265137)
Descriptors: MW 320.32, ALogP 4.45, HBA 3, HBD 3, PSA 69.14, QED 0.48
Compound (SMILES): COCCc1c[nH]c2ncnc(-c3ccc4c(c3)N(C#N)CCO4)c12
InChIKey: UEDWZOQXFUIRAN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 using KAIETDKEYYTVKD-NH2 as substrate in presence of 1 mM ATP concentration by coupled PK/LDH assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.37, ALogP 2.49, HBA 6, HBD 1, PSA 87.06, QED 0.74
Compound (SMILES): NCCCC[C@H](NC(=O)[C@@H](N)Cc1ccc(OCc2ccccc2)cc1)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCc1ccccc1
InChIKey: XBXPGZRFJLFNEC-IHPFPOKCSA-N
Target: Proteasome Macropain subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P49721
Assay: Inhibition of human 20S constitutive proteasome beta-2 using BocLRR-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 706.84, ALogP 2.78, HBA 8, HBD 7, PSA 197.9, QED 0.08
Compound (SMILES): Fc1ccc(F)c(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c1
InChIKey: GBMCYUDJVSXCST-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 420.35, ALogP 4.27, HBA 5, HBD 1, PSA 72.28, QED 0.49
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(F)c(OCc3ccc(F)cc3)c2)c1
InChIKey: JHDVDMCSBXSGFG-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 437.4, ALogP 4.4, HBA 6, HBD 1, PSA 86.47, QED 0.44
Compound (SMILES): O=C(NCc1ccccc1)C1CCN(C(=O)c2ccc(-c3ccccc3)cc2)CC1
InChIKey: PLXQZCKNWRLVJF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1E (SINGLE PROTEIN), Homo sapiens
UniProt: P28566
Assay: Displacement of [3H]5-HT from human 5HT1E receptor expressed in HEKT cell membranes after 1.5 hrs by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 398.51, ALogP 4.52, HBA 2, HBD 1, PSA 49.41, QED 0.69
Compound (SMILES): CC(C)(C)c1cc(/C=C/C(=O)NCCC2CCN(Cc3ccccc3F)CC2)cc(C(C)(C)C)c1O
InChIKey: RXSZVSISAHLZBD-VAWYXSNFSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B using p-tyramine as substrate incubated for 15 mins followed by substrate addition measured for 20 mins by fluorescence assay
Measurement: IC50 = 7400 nM (pChEMBL 5.130000114440918)
Descriptors: MW 494.7, ALogP 6.56, HBA 3, HBD 2, PSA 52.57, QED 0.43
Compound (SMILES): O=c1[nH]c2ccc(C3=NN=C(NCc4ccccc4)SC3)cc2[nH]1
InChIKey: PNJQHHXWPZEHTA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to DYRK1A (unknown origin) assessed as dissociation constant
Measurement: Kd = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 337.41, ALogP 2.45, HBA 5, HBD 3, PSA 85.4, QED 0.69
Compound (SMILES): Clc1cccc(Cn2cnc(-c3cc4[nH]nnc4cn3)c2)c1
InChIKey: WLHOJGUAXPKUMX-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: PHF8 Assay: The ability of test compounds to inhibit the activity of PHF8 was determined in 384-well plate format under the following reaction conditions: 3 nM PHF8, 200 nM H3K9me1-biotin labeled peptide (Anaspec cat #64358), 0.5 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified-histone H3 lysine 9/lysine27 (H3K9/K27) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 0.5 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 600 nM H3K9me1-biotin labeled peptide and 1.5 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 9 nM PHF8 to initiate the reaction. The reaction mixture was incubated at rt for 15 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 1 nM Europium-anti-unmodified H3K9/K27 antibody. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 310.75, ALogP 2.92, HBA 5, HBD 1, PSA 72.28, QED 0.63
Compound (SMILES): Cc1nn(-c2cc(C(=O)O)ccn2)c(O)c1C
InChIKey: ZTSZMVPLKHSHGA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 233.23, ALogP 1.29, HBA 5, HBD 2, PSA 88.24, QED 0.82
Compound (SMILES): FC(F)(F)CNc1nc(Nc2ccnc(C(F)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
InChIKey: PLCJHAPDBYLXRZ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 483.3, ALogP 5.08, HBA 7, HBD 2, PSA 88.51, QED 0.49
Compound (SMILES): C[C@@H](Nc1nc(N[C@H]2CCC[C@H]2O)nc(-c2cccc(C(F)(F)F)n2)n1)C1CC1
InChIKey: UHUHOBBXPQIHRY-SCDSUCTJSA-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 408.43, ALogP 3.49, HBA 7, HBD 3, PSA 95.85, QED 0.67
Compound (SMILES): COCC1(c2ccc(-c3c(-c4cc(C(=O)O)ccn4)ncn3C)cc2)CC1
InChIKey: IGZZKOJEHRREEV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 363.42, ALogP 3.53, HBA 5, HBD 1, PSA 77.24, QED 0.72
Compound (SMILES): Fc1ccc(Cn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)c(F)c1
InChIKey: LABVGZXSSYPADP-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 406.32, ALogP 4.08, HBA 5, HBD 1, PSA 72.28, QED 0.52
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)Cc1ccc(F)cc1
InChIKey: XBGIGBHCVFRAGP-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 354.39, ALogP 2.91, HBA 5, HBD 1, PSA 71.25, QED 0.71
Compound (SMILES): CC(C)C(c1ccccc1)n1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: OAHACOXPLGQGIK-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, ALPHASCREEN Streptavidin-coated Donor beads, and ALPHASCREEN Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at rt for 40 min, followed by addition of 3 μl of 50 μg/ml ALPHASCREEN Streptavidin-coated Donor beads and ALPHASCREEN Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 412.42, ALogP 4.99, HBA 5, HBD 1, PSA 72.28, QED 0.5
Compound (SMILES): Cc1ccc(CCn2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)cc1
InChIKey: LVTPIPCJSJQBGO-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at rt for 30 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 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 398.39, ALogP 4.3, HBA 5, HBD 1, PSA 72.28, QED 0.54
Compound (SMILES): CC(Oc1cc(Cl)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1)c1ccccc1
InChIKey: GBJNSFXBUOTPIV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Jarid1B Assay: The ability of test compounds to inhibit the activity of Jarid1B was determined in 384-well plate format under the following reaction conditions: 0.8 nM Jarid1B, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of the plate, followed by the addition of 2 μl of 2.4 nM Jarid1B to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 449.89, ALogP 5.34, HBA 6, HBD 1, PSA 86.47, QED 0.39
Compound (SMILES): O=C(NCc1ccc(OC(F)(F)F)c(Cl)c1)c1ccc(S(=O)(=O)Nc2ncns2)c(F)c1
InChIKey: FXTBLDWXLZMPPV-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human NaV1.6
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 510.88, ALogP 3.96, HBA 7, HBD 2, PSA 110.28, QED 0.47
Compound (SMILES): CCNC(=O)c1ccc(-c2c(C)nc3c(Oc4ccccc4)cccn23)cn1.Cl
InChIKey: IQBKJXPPXJHJOZ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 372.43, ALogP 4.25, HBA 5, HBD 1, PSA 68.52, QED 0.57
Compound (SMILES): Fc1ccc(C2CCn3nc(N[C@@H]4[C@@H]5CC[C@H]4CN(c4ccnc(C(F)(F)F)c4)C5)nc32)cc1F
InChIKey: GDNQPTLFLSJXDP-AHVKTYSCSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma secretase in human H4 cells overexpressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in total amyloid beta (1 to 42 residues) production measured after 24 hrs by AlphaLISA assay
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 490.48, ALogP 4.83, HBA 6, HBD 1, PSA 58.87, QED 0.53
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3C[C@@H](O)C[C@H]3C(=O)O)cc2Cl)cccc1-c1cccnc1
InChIKey: HYPNJZJIMUEFNZ-FIBWVYCGSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 584.07, ALogP 5.76, HBA 7, HBD 2, PSA 115.91, QED 0.24
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3CCNCC3)cc2Cl)cccc1-c1ccc2c(c1)OCCO2
InChIKey: OTDNXXUMUVZTPE-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 = 232.9 nM (pChEMBL 6.630000114440918)
Descriptors: MW 596.13, ALogP 6.52, HBA 7, HBD 1, PSA 75.98, QED 0.24
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3CC[C@H](C(=O)O)C3)cc2Cl)cccc1-c1ccc2c(c1)OCCO2
InChIKey: XUVGXIRFSMZJHA-MHZLTWQESA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 625.12, ALogP 7.02, HBA 7, HBD 1, PSA 101.25, QED 0.2
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3CCCC[C@H]3C(=O)O)cc2Cl)cccc1-c1cccnc1
InChIKey: XTLJKNFJQWLWOY-HKBQPEDESA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 582.1, ALogP 7.18, HBA 6, HBD 1, PSA 95.68, QED 0.21
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)OC(C)C)C(=O)N[C@@H](CC(F)(F)F)C(=O)NCCc1ccc(C(=O)O)cc1Cl
InChIKey: FOBANMWDMXKVPX-UFYCRDLUSA-N
Target: Hepatitis C virus serine protease, NS3/NS4A (PROTEIN COMPLEX), Hepatitis C virus
UniProt: A3EZI9
Assay: Inhibition of HCV NS3/4a protease
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 653.05, ALogP 2.64, HBA 7, HBD 6, PSA 200.23, QED 0.16
Compound (SMILES): Clc1cccc2c(-n3cnc4c(-c5nnc[nH]5)cc(N5CCOCC5)cc43)ccnc12
InChIKey: GDZNVPWDBYHIJL-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110beta/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 431.89, ALogP 3.85, HBA 7, HBD 1, PSA 84.75, QED 0.47
Compound (SMILES): C[C@@H]1CN(c2nc(-c3cnn(C)c3)ncc2C#N)CCN1C(=O)C1(C)CC1
InChIKey: MSDVUBZPLFKQFG-CYBMUJFWSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged p110delta/untagged full-length p85alpha expressed in baculovirus infected Sf21 cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 365.44, ALogP 1.59, HBA 7, HBD 0, PSA 90.94, QED 0.82
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O
InChIKey: AWPNCYPNCSCZFL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of human CDK4/cyclin-D1 using RB protein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 831.94, ALogP 3.09, HBA 15, HBD 4, PSA 220.93, QED 0.08
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN[C@@H](C(=O)O)[C@H](C)O)cc2Cl)cccc1-c1ccccc1
InChIKey: HQLXLYKMGOZHJV-GHRAFVERSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 571.07, ALogP 6.27, HBA 6, HBD 3, PSA 111.81, QED 0.18
Compound (SMILES): C[C@H](CCCNCc1ccccn1)[C@H]1CC[C@@]2(C)[C@@H]3CC=C4[C@@H](CC[C@H](O)C4(C)C)[C@]3(C)[C@H](O)C[C@]12C
InChIKey: XKKWYKBUGVUDQA-OXQNSESWSA-N
Target: AMPK alpha2/beta1/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y478
Assay: Allosteric activation of AMPK alpha2/beta1/gamma1 in human HepG2 cells by scintillation proximity assay
Measurement: EC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 508.79, ALogP 6.52, HBA 4, HBD 3, PSA 65.38, QED 0.29
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3c(OCC(F)(F)F)ccc(C(F)(F)F)n3n2)sn1
InChIKey: OEAFCPTWSOXDBU-DRXBFXEBSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma secretase in human H4 cells over expressing human APP695 harboring K595N/M596L Swedish double mutant assessed as reduction in Abeta42 production after 24 hrs by Alphalisa assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 506.48, ALogP 4.78, HBA 8, HBD 1, PSA 67.58, QED 0.5
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3CCC(O)C3)cc2Cl)cccc1-c1ccc2c(c1)OCCO2
InChIKey: NCJACZWANLIGQL-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 597.11, ALogP 6.68, HBA 7, HBD 1, PSA 84.18, QED 0.23
Compound (SMILES): CCNC(=O)N1C[C@@H]2C[C@H]1CN2c1nc(-c2cnn(C)c2)ncc1C#N
InChIKey: CCUFTWMGUUIZJE-KBPBESRZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged p110delta/untagged full-length p85alpha expressed in baculovirus infected Sf21 cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 2191 nM (pChEMBL 5.659999847412109)
Descriptors: MW 352.4, ALogP 0.74, HBA 7, HBD 1, PSA 102.97, QED 0.87
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NCCc4ccccc4)n3)nc2)CC1
InChIKey: VBACZDJYOLHJGZ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Inhibition of recombinant human full-length N-terminal His-tagged CDK6/cyclinD3 expressed in baculovirus infected Sf9 insect cells using histone H1 as substrate measured after 60 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.95, ALogP 3.68, HBA 7, HBD 2, PSA 69.21, QED 0.6
Compound (SMILES): Cl.Clc1cc(OC[C@@H]2C[C@H]3C[C@H]3N2)cnc1Cl
InChIKey: WWGMRWGWJXJQII-FGGSWVFUSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P17787
Assay: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method
Measurement: Ki = 149.2 nM (pChEMBL 6.829999923706055)
Descriptors: MW 259.14, ALogP 2.52, HBA 3, HBD 1, PSA 34.15, QED 0.85
Compound (SMILES): Cc1c(COc2cc(OCc3cccc(C#N)c3)c(CN3C[C@@H](O)C[C@@H]3CO)cc2Cl)cccc1-c1ccc2c(c1)OCCO2
InChIKey: UFLMZUYQFOUJIV-IHLOFXLRSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 = 11.1 nM (pChEMBL 7.960000038146973)
Descriptors: MW 627.14, ALogP 6.04, HBA 8, HBD 2, PSA 104.41, QED 0.22
Compound (SMILES): CCN1C(=O)c2ccc(-c3c(C)nc4c(OCc5ccccc5)cccn34)cc2C1(C)C.Cl
InChIKey: VQENLMFJGDXNLE-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulatory activity of gamma secretase in human SKNBE2 cells assessed as decrease in Abeta42 levels incubated for 6 hrs by sandwich ELISA
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 425.53, ALogP 5.6, HBA 4, HBD 0, PSA 46.84, QED 0.42
Compound (SMILES): CC(=O)NCCNCc1ccc2oc(-c3cccc(-c4ccccc4)c3C)cc(=O)c2c1
InChIKey: CUVPSRMKNYEUEU-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 426.52, ALogP 4.66, HBA 4, HBD 2, PSA 71.34, QED 0.42