lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-c2cc(NC(C)c3cccc(-c4cnn(C)c4)c3)nc(C)n2)c(F)c1
InChIKey: ACWPOUREYFAPKF-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 417.49, ALogP 5.17, HBA 6, HBD 1, PSA 64.86, QED 0.47
Compound (SMILES): Cc1nc(NCC2CCCN(C(=O)C3CCCCC3)C2)cc(-c2ccc3ncsc3c2)n1
InChIKey: ARPKCPDYKLZDCV-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 449.62, ALogP 5.29, HBA 6, HBD 1, PSA 71.01, QED 0.57
Compound (SMILES): Cc1nc(NC(C)c2cccc(-c3cnn(C)c3)c2)cc(-c2cccc(N(C)C)c2)n1
InChIKey: RBLRPPZBVGYIIG-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 412.54, ALogP 5.09, HBA 6, HBD 1, PSA 58.87, QED 0.48
Compound (SMILES): Cc1nc(NCCC(C)C)cc(-c2ccc3ncsc3c2)n1
InChIKey: GKHHXTGNEOBPAG-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 312.44, ALogP 4.52, HBA 5, HBD 1, PSA 50.7, QED 0.75
Compound (SMILES): Cc1nc(NCCC2=CCCCC2)cc(-c2ccc3ncsc3c2)n1
InChIKey: AYNGCOOTVNNCRN-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 350.49, ALogP 5.36, HBA 5, HBD 1, PSA 50.7, QED 0.63
Compound (SMILES): Cc1nc(NCCc2ccc(O)cc2)cc(-c2ccc3ncsc3c2)n1
InChIKey: UAWXXOSNZGODFT-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 362.46, ALogP 4.42, HBA 6, HBD 2, PSA 70.93, QED 0.55
Compound (SMILES): CCCCCNc1cc(-c2ccc3ncsc3c2)nc(C)n1
InChIKey: IUBXXTSPDXEXKM-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 312.44, ALogP 4.66, HBA 5, HBD 1, PSA 50.7, QED 0.67
Compound (SMILES): CCC(C)Nc1cc(-c2ccc3ncsc3c2)nc(C)n1
InChIKey: WWSUPIKKQUTGJD-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 298.42, ALogP 4.27, HBA 5, HBD 1, PSA 50.7, QED 0.78
Compound (SMILES): CCCCCC(C)Nc1cc(-c2ccc3ncsc3c2)nc(C)n1
InChIKey: DLZXDMUCTXQONK-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 340.5, ALogP 5.44, HBA 5, HBD 1, PSA 50.7, QED 0.58
Compound (SMILES): Cc1nc(N[C@@H](C)C(C)(C)C)cc(-c2ccc3ncsc3c2)n1
InChIKey: RCDNLLBAFSXAKI-NSHDSACASA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 326.47, ALogP 4.91, HBA 5, HBD 1, PSA 50.7, QED 0.74
Compound (SMILES): Cc1nc(NCCc2ccccn2)cc(-c2ccc3ncsc3c2)n1
InChIKey: SVEDIEHYYAMZIF-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 347.45, ALogP 4.11, HBA 6, HBD 1, PSA 63.59, QED 0.59
Compound (SMILES): COCC(C)Nc1cc(-c2ccc3ncsc3c2)nc(C)n1
InChIKey: VZZYHGTZSWUJOS-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 314.41, ALogP 3.51, HBA 6, HBD 1, PSA 59.93, QED 0.78
Compound (SMILES): Cc1nc(N[C@@H](C)c2cccc(-c3ccn[nH]3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: DLQTVGWZCGIELL-AWEZNQCLSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 412.52, ALogP 5.62, HBA 6, HBD 2, PSA 79.38, QED 0.39
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCC(=O)NCCN(C)C)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: MAPWSKMTGHYHKW-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 490.63, ALogP 4.29, HBA 8, HBD 2, PSA 92.27, QED 0.34
Compound (SMILES): CCN(C)C(=O)COc1cccc(C(C)Nc2cc(-c3ccc4ncsc4c3)nc(C)n2)c1
InChIKey: QNQASJOEYPKGBB-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 461.59, ALogP 5.09, HBA 7, HBD 1, PSA 80.24, QED 0.39
Compound (SMILES): Cc1nc(NC(C)c2cccc([N+](=O)[O-])c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: LCAFVWSAWDUOOS-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 391.46, ALogP 5.14, HBA 7, HBD 1, PSA 93.84, QED 0.37
Compound (SMILES): Cc1nc(N[C@@H](C)c2cccc(/C=C/C(=O)NC(C)(C)C)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: CNLDOHAUTBKTJR-KQPPXVQYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 471.63, ALogP 6.16, HBA 6, HBD 2, PSA 79.8, QED 0.33
Compound (SMILES): Cc1nc(NC(C)c2cccc(N)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: AQJJKPKWPGUXCB-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 361.47, ALogP 4.82, HBA 6, HBD 2, PSA 76.72, QED 0.51
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCc3nc(C(=O)O)co3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: ZUIQFSPDZICBSR-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 487.54, ALogP 5.5, HBA 9, HBD 2, PSA 123.26, QED 0.29
Compound (SMILES): COC(=O)c1coc(COc2cccc(C(C)Nc3cc(-c4ccc5ncsc5c4)nc(C)n3)c2)n1
InChIKey: YLIZKEACHSWMHJ-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 501.57, ALogP 5.59, HBA 10, HBD 1, PSA 112.26, QED 0.27
Compound (SMILES): Cc1nc(N[C@@H](C)c2ccccc2)cc(-c2ccc3ncsc3c2)n1
InChIKey: AESSXTRSSCNWDZ-ZDUSSCGKSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 346.46, ALogP 5.23, HBA 5, HBD 1, PSA 50.7, QED 0.55
Compound (SMILES): Cc1nc(NC2CC(C)(C)Oc3ccccc32)cc(-c2ccc3ncsc3c2)n1
InChIKey: RTALZVOFOYCSGX-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 402.52, ALogP 5.78, HBA 6, HBD 1, PSA 59.93, QED 0.47
Compound (SMILES): Cc1nc(NC(C)c2cccc(-c3ccoc3)c2)cc(-c2ccc3occ(C)c3c2)n1
InChIKey: ZSMXKGYXVUCSNI-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 409.49, ALogP 6.94, HBA 5, HBD 1, PSA 64.09, QED 0.34
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCc3ccccc3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: MUZYWGGZQMZDEN-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 452.58, ALogP 6.81, HBA 6, HBD 1, PSA 59.93, QED 0.29
Compound (SMILES): Cc1nc(NC(C)c2cccc(-c3ccsc3)c2)cc(-c2ccc3occ(C)c3c2)n1
InChIKey: OURRZYDYVHFMLH-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 425.56, ALogP 7.41, HBA 5, HBD 1, PSA 50.95, QED 0.32
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCc3cccnc3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: INLDUOBAZXMCSD-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 453.57, ALogP 6.21, HBA 7, HBD 1, PSA 72.82, QED 0.32
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCc3csc(C)n3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: ZUJUBCFXXWMNQN-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 473.63, ALogP 6.58, HBA 8, HBD 1, PSA 72.82, QED 0.29
Compound (SMILES): CCCOc1cccc(C(C)Nc2cc(-c3ccc4ncsc4c3)nc(C)n2)c1
InChIKey: NWRZKFOSOJKRHM-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 404.54, ALogP 6.02, HBA 6, HBD 1, PSA 59.93, QED 0.41
Compound (SMILES): Cc1nc(NC(C)c2cccc(-c3c(C)noc3C)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: VAPYKEFWDLQTJD-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.56, ALogP 6.51, HBA 7, HBD 1, PSA 76.73, QED 0.34
Compound (SMILES): Cc1nc(N[C@@H]2CCCc3ccccc32)cc(-c2ccc3c(c2)C(=O)C=CC3)n1
InChIKey: FTWNNSJAKPNHEH-JOCHJYFZSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 381.48, ALogP 5.24, HBA 4, HBD 1, PSA 54.88, QED 0.67
Compound (SMILES): Cc1ccc(COc2cccc(C(C)Nc3cc(-c4ccc5ncsc5c4)nc(C)n3)c2)cc1
InChIKey: QROHLCDIGXCODS-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 466.61, ALogP 7.12, HBA 6, HBD 1, PSA 59.93, QED 0.28
Compound (SMILES): Cc1nc(NC(C)c2cccc(-c3ccoc3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: CVJDNPWMXYWRTN-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 412.52, ALogP 6.49, HBA 6, HBD 1, PSA 63.84, QED 0.36
Compound (SMILES): Cc1ccc(OCc2noc(COc3cccc(C(C)Nc4cc(-c5ccc6ncsc6c5)nc(C)n4)c3)n2)cc1
InChIKey: ICQVAJCZIQIMIQ-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 564.67, ALogP 7.08, HBA 10, HBD 1, PSA 108.08, QED 0.19
Compound (SMILES): Cc1nc(NC(C)c2cccc(-c3ccsc3)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: YFAHUKOXGOQRAB-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 428.59, ALogP 6.96, HBA 6, HBD 1, PSA 50.7, QED 0.33
Compound (SMILES): Cc1nc(N[C@@H]2CCCc3ccccc32)cc(-c2ccc3nonc3c2)n1
InChIKey: VENJSALARSNZSU-QGZVFWFLSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 357.42, ALogP 4.48, HBA 6, HBD 1, PSA 76.73, QED 0.58
Compound (SMILES): COc1cccc(Oc2cc(N[C@@H]3CCCc4ccccc43)nc(C)n2)c1
InChIKey: REOKOKPYRGUFOH-HXUWFJFHSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring NADH absorbance pre-incubated for 10 mins before ATP/substrate addition followed by incubation for 1 hr by UV-Visible spectrometry based iPFK-2/PPI-PFK coupled enzyme assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 361.45, ALogP 5.08, HBA 5, HBD 1, PSA 56.27, QED 0.69
Compound (SMILES): Cc1nc(N[C@@H]2CCCc3ccccc32)cc(-c2ccc3c(ccn3C)c2)n1
InChIKey: GRXFLEFNXWRRCF-OAQYLSRUSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 368.48, ALogP 5.43, HBA 4, HBD 1, PSA 42.74, QED 0.52
Compound (SMILES): Cc1nc(N[C@@H]2CCCc3ccccc32)cc(-c2cnc3ccccc3c2)n1
InChIKey: ULCAVCXZLULUCF-JOCHJYFZSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 366.47, ALogP 5.49, HBA 4, HBD 1, PSA 50.7, QED 0.52
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCCF)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: FMNHBLNRQXKTCV-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 408.5, ALogP 5.58, HBA 6, HBD 1, PSA 59.93, QED 0.43
Compound (SMILES): Cc1nc(NC(C)c2cccc(OCC(F)(F)F)c2)cc(-c2ccc3ncsc3c2)n1
InChIKey: QHUAYRHAOSAIGN-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 444.48, ALogP 6.18, HBA 6, HBD 1, PSA 59.93, QED 0.39
Compound (SMILES): Cc1nc(NC(C)c2ccc(F)c(Br)c2)cc(-c2ccc3occ(C)c3c2)n1
InChIKey: SYCSUEZTDSPFCL-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 440.32, ALogP 6.58, HBA 4, HBD 1, PSA 50.95, QED 0.39
Compound (SMILES): Cc1nc(N[C@H](C)c2ccc(F)c(-c3cnn(C)c3)c2)cc(-c2ccc3occ(C)c3c2)n1
InChIKey: WVPAXRWJLFOGJF-MRXNPFEDSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of iPFK2 (unknown origin) assessed as reduction in enzyme-mediated fructose-6-phosphate phosphorylation by measuring ATP consumption incubated for 3 hrs by luciferase-luciferin-coupled chemiluminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.51, ALogP 6.22, HBA 6, HBD 1, PSA 68.77, QED 0.35
Compound (SMILES): O=C(NCCN1CCNC1=O)[C@H]1[C@H](C(=O)Nc2ncc(Br)s2)[C@@H]2C=C[C@H]1C21CC1
InChIKey: HNXIVNAAKLQIBA-ZMJPVWNMSA-N
Target: N-formyl peptide receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25089
Assay: Agonist activity at human recombinant FPRL2 receptor expressed in HEK293 cells co-expressing G-protein Galpha16 assessed as effect on calcium response by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 = 8730 nM (pChEMBL 5.059999942779541)
Descriptors: MW 480.39, ALogP 1.81, HBA 5, HBD 3, PSA 103.43, QED 0.54
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@@H](C)O)n1)c1ccc(OC(F)(F)F)cc1
InChIKey: MBCIKYUWMXLUQE-MISXGVKJSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Fluorescence Biochemical Assay: The IDH1 (R132H) mutant catalyzes the reduced form of NADP+ (NADPH) and α-ketoglutarate (α-KG) to form nicotinamide adenine dinucleotide phosphate (NADP+) and R (−)-2-hydroxyglutarate (2HG). The reaction can be monitored kinetically by following the oxidation of NADPH to NADP+ which is measured using fluorescence, excitation at 355 nm and emission at 530 nm. Reactions were monitored using the Perkin-Elmer Envision, Model 2101. More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Cat. No. 781076) using a final reaction volume of 20 μL and the following assay buffer conditions: 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.02% BSA, 0.02% Tween-20, 10 μM NADPH and 100 μM α-KG. The final reaction mixture contained 2.5% DMSO and test compounds with concentrations ranging 0.0000008-25 μM. The IDH1 (R132H) enzyme was used at a final concentration of 10 nM.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 412.37, ALogP 3.25, HBA 7, HBD 2, PSA 96.81, QED 0.75
Compound (SMILES): O=C(NCc1c(Cl)cc(Cl)cc1COCCO)C1COc2ncccc21
InChIKey: XOMZGLXVHMQEEG-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: YO-PRO Assay: HEK cells stably expressing P2X7 were used to screen drugs using the YO-PRO1 assay. Cells were grown to confluency in adherent culture at 37° C. in a humidified 5% CO2 incubator (split ⅕ every 3-4 days with DMEM, 10% FCS, 1% Penicillin/Streptomycin, 250 μg/ml Geneticin). Adherent cells were detached by incubation with Trypsine (1 ml per 165 cm2 dish) for 2 minutes, then washed off with 10 ml PBS (without Mg2+ and Ca2+), and resuspended in DMEM, 10% FCS, 1% Penicillin/Streptomycin, no Geneticin. 10,000 cells per well (48 hours before the assay) or 25,000 cells per well (Vi-cell XR (Beckman Coulter) (24 hours before the assay) in 50 μl full medium were seeded on 384-well black-wall, clear bottom plates, that were coated before with 10 μl per well Poly-L-Lysine, incubated for 30-60 minutes at 37° C. and washed once with PBS. Medium was removed from cells and 50 μl of assay buffer containing 0.5 μM YO-PRO-1 was added into the wells. Solutions of antagonist compounds were prepared by serial dilutions of a 10 mM DMSO solution of the antagonist into PBS using a BioMek (Beckman Coulter). Each concentration was performed in duplicate. For IC50 measurements 10 concentration points were measured (10 μM being the highest concentration followed by 9 serial dilution steps ⅓). The cells were incubated with the antagonists of the present invention together with ATP at a final concentration of 250 μM for 90 minutes. During this time period, four time points were taken. Each time point comprised the average of several measurements made within a few seconds. Fluorescence was measured in the FLIPR tetra (Molecular Devices) using the filters appropriate for YO-PRO-1 fluorescence (excitation485/20, emission 530/25).
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 397.26, ALogP 2.69, HBA 5, HBD 2, PSA 80.68, QED 0.7
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)c1ccc(-c2ccc(NC(=O)CNC(=O)CN3CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC3)cc2C)cc1)C(C)C)C(N)=O
InChIKey: QWQLTABBWDIBTN-YBDACEPQSA-N
Target: Gastrin-releasing peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30550
Assay: Displacement of [125I]-BBN from GRPR in human PC3 cells after 1 hr by compuGamma counting or microplate scintillation counting method
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 1592.85
Compound (SMILES): Cc1ccc(-n2nc(C3CCN([S+]([O-])c4cccc5ccccc45)CC3)cc2NC(=O)c2cnn3cccnc23)cc1
InChIKey: DAADAOFTTCPMCK-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Kinase Assay: The kinase activity of IRAK-4 is determined by its ability to catalyze the phosphorylation of a fluorescent polypeptide substrate. The extent of phosphorylation is measured using the IMAP technology (Molecular Devices) where the phosphorylated fluorescent substrate binds to the large M(III)-based nanoparticles which reduces the rotational speed of the substrate and thus increases its fluorescent polarization (FP). 20 μl reaction mixture contains 10 mM TriHCl, pH 7.2, 0.5 nM GST tagged IRAK-4 (SignalChem), 100 nM fluorescent peptide substrate (RP7030, Molecular Devices), 100 μM ATP, 1 mM DTT, 1 mM MgCl2, and 0.01% Tween 20. The reaction is initiated by the addition of ATP. After incubation for 30 minutes at 25° C., 60 μl of Progressive IMAP Reagent (Molecular Devices) is added to stop the reaction. Change in RP7030's FP is determined by a FP reader (Analyst HT, LH, BioSystems).
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 575.7, ALogP 5.53, HBA 8, HBD 1, PSA 103.41, QED 0.26
Compound (SMILES): CC(C)CN(Cc1ccc(N2CCC(CS(C)(=O)=O)CC2)cc1)S(=O)(=O)Cc1ccccc1
InChIKey: DIBBUQZSPCWIMZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: In Vitro Assay: On day of the assay, 100 uL of 0.05% CHAPS (in deionized H2O) was added to all wells of the GFB Unifilter plate and allowed soak for 1 h. A wash buffer of 50 mM HEPES (pH 7.4), 150 mM NaCl, and 5 mM MgCl2 was prepared to wash the filter plate. To prepare an assay buffer, BSA was added to the wash buffer to reach 0.01% and DTT was added to reach 1 mM. For IC50 mode, 10 mM compound stocks were serially diluted in DMSO with DMSO to give 20x required final concentration in DMSO (15 uL compound+30 uL DMSO). The 20x compound stocks were diluted in DMSO with Assay Buffer 4-fold to reach 5x the final test concentration in 25% DMSO (10 uL compound+30 uL Assay Buffer). Solutions were mixed by aspiration several times with a pipette set on 50 uL volume. For the assay, 10 uL of 5x compound stock solutions in 25% DMSO were added to the assay plate in duplicate.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 492.71, ALogP 3.94, HBA 5, HBD 0, PSA 74.76, QED 0.5
Compound (SMILES): CCc1ncc(F)cc1[C@H]1CCCN1c1ccn2ncc(C(=O)NC3CCC(O)CC3)c2n1
InChIKey: COJJJJKXTCQCLW-MYKUNDNFSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 452.53, ALogP 3.2, HBA 7, HBD 2, PSA 95.65, QED 0.62
Compound (SMILES): CNC(=O)c1cccc(Nc2ncnc(N3CCc4ccc(OC)cc4C3)n2)c1
InChIKey: WACAEXNJBICZPC-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Cell-Based Assay: Compounds were tested on human Nav1.7 (hNav1.7) expressed stably in 293 cells, which have no endogenous sodium channels. Two forms of whole-cell patch-clamp assays were used. In both, peak current through Nav1.7 was evoked by a depolarizing voltage pulse, and currents were monitored as a function of time in response to exposure to several different concentrations of drug. Automated electrophysiology uses the PatchXpress 7000A system. Up to sixteen cells at a time were voltage-clamped in parallel, and the steady-state voltage dependence of inactivation was determined experimentally for each cell. For each cell, fractional inactivation was set at 20%, and peak current through Nav1.7 as a function of time was measured in response to increasing concentrations of test compound. Manual electrophysiology refers to conventional whole-cell patch-clamping (Hamill et al., 1981). After formation of the whole-cell clamp, cells were lifted off the bottom of the dish with the patch pipette and positioned directly in front of an array of glass microperfusion tubes each with internal diameter about 250 microns, with individual compound concentrations flowing from each tube. Current as a function of time in response to increasing drug concentrations was measured with Nav1.7 fully in the resting state (holding voltage set to −140 mV) and on the same cells with the holding voltage set to produce about 20% inactivation. Compounds were not applied for a prespecified time, but for as long as required to achieve a stable level of block.
Measurement: IC50 = 8850 nM (pChEMBL 5.050000190734863)
Descriptors: MW 390.45, ALogP 2.55, HBA 7, HBD 2, PSA 92.27, QED 0.69
Compound (SMILES): Cn1c(Nc2c(F)cccc2Cl)nc2nc(C(=O)Nc3cc(F)cc(C(F)(F)F)c3)c3c(c21)OCCO3
InChIKey: HCKYIIINRPZAPO-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of human recombinant mPGES-1 expressed in CHO cells assessed as reduction in conversion of PGH2 to PGE2 incubated for 10 mins followed by substrate addition measured after 1 min in presence of GSH
Measurement: IC50 = 415.1 nM (pChEMBL 6.380000114440918)
Descriptors: MW 539.85, ALogP 5.69, HBA 7, HBD 2, PSA 90.3, QED 0.32
Compound (SMILES): CC(c1nc2c(cnn2C2CCOCC2)c(=O)[nH]1)N1CC(Oc2cccc(OC(F)(F)F)c2)C1.O=C(O)C(F)(F)F
InChIKey: JASFNJYMYBMKHY-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: Inhibition of human recombinant PDE9 expressed in insect Sf9 cells using [3H]-cGMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 48.9 nM (pChEMBL 7.309999942779541)
Descriptors: MW 479.46, ALogP 3.19, HBA 8, HBD 1, PSA 94.5, QED 0.58
Compound (SMILES): O=C(CCn1cccc1)N1CC=C(c2ccc(NC(=O)N3Cc4ccncc4C3)cc2)CC1
InChIKey: HECMHVAEXIWMDT-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay : Probe 2:The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb-anti-His antibody (Invitrogen, Cat #PV5895), and 200 nM probe (Oregon Green 488-conjugated APO0866; A-1287128.0. Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
Measurement: IC50 = 2.95 nM (pChEMBL 8.529999732971191)
Descriptors: MW 441.54, ALogP 4.14, HBA 4, HBD 1, PSA 70.47, QED 0.65
Compound (SMILES): CSc1cccc(CNc2nc(NC3CC3)n3ncc(/C=C4\NC(=O)NC4=O)c3n2)c1
InChIKey: AGHHWRIONRDRFU-NVNXTCNLSA-N
Target: Casein kinase II subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P67870
Assay: Inhibition Assay: Test compounds dissolved and diluted in DMSO (2 μl) were added to a reaction mixture comprising 10 μl of 5× Reaction Buffer (40 mM MOPS pH 7.0, 5 mM EDTA), 10 μl of recombinant human PIM2 solution (4 ng PIM-2 dissolved in dilution buffer (20 mM MOPS pH 7.0; EDTA 1 mM; 5% Glycerol; 0.01% Brij 35; 0.1%; 0.1% 2-mercaptoethanol; 1 mg/ml BSA)) and 8 ul of water. Reactions were initiated by the addition of 10 ul of ATP Solution (49% (15 mM MgCl2; 75 uM ATP) 1% ([γ-33P]ATP: Stock 1 mCi/100 μl; 3000 Ci/mmol (Perkin Elmer)) and 10 ul of substrate peptide solution (RSRSSYPAGT (SEQ ID NO.: 6), dissolved in water at a concentration of 1 mM), Reactions were maintained for 10 min at 30° C. The reactions were quenched with 100 ul of 0.75% Phosphoric acid, then transferred to and filtered through a Phosphocellulose filter plate (Millipore, MSPH-N6B-50). After washing each well 4 times with 0.75% Phosphoric acid, scintillation fluid (20 uL) was added to each well and the resid
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 436.5, ALogP 2.21, HBA 9, HBD 4, PSA 125.34, QED 0.25
Compound (SMILES): CC1CO[C@H]2CCC[C@@H]2N1c1nc2cc(-c3nc(=O)o[nH]3)nc(-c3cncc(Cl)c3)c2n1C[C@H]1CC[C@H](C)CC1
InChIKey: IZXXIUQNDFXYJM-CHFLRFAMSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 564.09, ALogP 5.46, HBA 9, HBD 1, PSA 114.96, QED 0.34
Compound (SMILES): COc1cc(Oc2nccc(C)n2)ccc1-c1cc2c(cc1F)ncc1ncn(C3(C)CCN(C(N)=O)CC3)c12
InChIKey: SOLZIGXKXMEQFO-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Radioactive Binding Assay: The radioactive filter binding assay is standardized using recombinant human activated BRAF (V599E) kinase (Cat No. 14-557) and kinase dead MEK1 (K97R) (Cat No. 14-737) procured from Upstate. The incorporation of 32P into MEK1 (K97R) by BRAF (V599E) is measured with final assay buffer conditions of 50 mM Tris pH 7.5, 10 mM MgCl2, 1 mM DTT, 100 mM sucrose, 100 μM sodium orthovanadate, 5 μM ATP and 2 μCi [γ 32P] ATP and 500 mg MEK1 Kinase dead substrate. The enzymatic reaction is stopped after 120 minutes with 8N HCl (hydrochloric acid) and 1 mM ATP. The solution is spotted on P81 filter paper and washed 4 times with 0.75% orthophosphoric acid and lastly with acetone. The dried P81 filter papers are read in a Micro-beta Trilux scintillation counter. The final concentration of DMSO is 1% in the assay. Compounds are screened at 10 μM concentration with pre-incubation of the enzymes in the presence of test compound for 45 minutes. Compounds of the invention were found to be inactive in this assy, e.g. ex. 33 (13% inhibition at 10 uM), ex. 1A (0% inhibition at 10 uM).
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 541.59, ALogP 5.18, HBA 8, HBD 1, PSA 121.28, QED 0.33
Compound (SMILES): Cc1cc2cc(/N=c3\[nH]c(=O)n(C[C@H](C)C(=O)O)c(=O)n3Cc3ccc(Cl)cc3)ccc2o1
InChIKey: GPQGUBKNQPAVJT-ZDUSSCGKSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Inhibition Assay: Stably expressing cell line (C6BU-1 cell transfected with human P2X3 receptor gene (GenBank accession number Y07683)) was used. The cells were seeded in a 96-well microtiter plate at a concentration of 8000 cells/well and cultured in the medium (8.3% fetal bovine serum, 8.3% horse serum, 1% antibiotic and antifungal in DMEM) for one day at 37 C. under 5% carbon dioxide atmosphere. The medium was replaced with 4 uM Fluo-3-AM solution (pH 7.5) containing 20 mM HEPES, 137 mM NaCl, 2.7 mM KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, 10% BSA, and 0.08% Pluronic F-127, and incubated at 37° C. under 5% dioxide carbon atmosphere for one hour. The plate was washed with washing buffer (20 mM HEPES, 137 mM NaCl, 2.7 mM KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, pH 7.5), and each well was added with 40 uL of this buffer. The plate was placed in High-Throughput Screening System FDSS 3000 (Hamamatsu Photonics K.K.).
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 468.9, ALogP 3.05, HBA 7, HBD 2, PSA 122.59, QED 0.45
Compound (SMILES): O=C(c1cccc(Cc2n[nH]c(=O)c3c2CCCC3)c1)N(CCO)Cc1ccccc1
InChIKey: JULCUXOTELNIQF-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: PARP Enzyme Inhibition Assay: PARP1 assay was conducted in PARP assay buffer containing 50 mM Tris pH 8.0, 1 mM DTT, 4 mM MgCl2. PARP reactions contained 1.5 uM [3H]-NAD+ (1.6 uCi/mmol), 200 nM biotinylated histone H1, 200 nM sIDNA, and 1 nM PARP enzyme. Auto reactions utilizing SPA bead-based detection were carried out in 100 uL volumes in white 96 well plates. Reactions were initiated by adding 50 ul of 2xNAD+ substrate mixture to 50 uL of 2x enzyme mixture containing PARP and DNA. These reactions were terminated by the addition of 150 uL of 1.5 mM benzamide (~1000-fold over its IC50). 170 uL of the stopped reaction mixtures were transferred to streptavidin Flash Plates, incubated for 1 hour, and counted using a TopCount microplate scintillation counter.
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 417.51, ALogP 2.87, HBA 4, HBD 2, PSA 86.29, QED 0.62
Compound (SMILES): C[C@H]1OC(=O)[C@]2(NC3CCC3)CC(F)(F)[C@@H](C)[C@H](/C=C/c3ccc(-c4ccccc4C#N)cn3)C12
InChIKey: YEIJVBSBHCKNMR-CTSDQTHLSA-N
Target: Proteinase-activated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25116
Assay: FLIPR Assay: HEK 293 Cells were grown in media containing DMEM, 10% FBS pen/strep/L-Glutamine and non-essential amino acids. The cells were plated in 384-well PDL coated plates at 12000 cells/well and incubated overnight at 37° C./5% CO2. Media was then removed from the cells, which were then incubated with buffer (Hank's containing HEPES and Chaps) containing FLIPR calcium-5 dye, made with buffer containing probenecid, for 60 minutes at 37° C. Varying concentrations of compound in a final concentration of 5% DMSO were then added to the cells and incubated at 25° C. for 30 minutes. The plates were then added to the FLIPR Tetra and the device added a concentration of a PAR1 selective receptor-activating peptide with the sequence Ala-parafluoroPhe-Arg-Cha-Cit-Try-Nh2 (prepared in water) at a concentration equal to the effective concentration that achieves 80% activation of signaling on the day of the experiment.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 477.56, ALogP 5.37, HBA 5, HBD 1, PSA 75.01, QED 0.59
Compound (SMILES): C[C@H]1OC(=O)[C@]2(NC(=O)CC(C)(C)C)CC(F)(F)[C@@H](C)[C@H](/C=C/c3ccc(-c4ccccc4C#N)cn3)[C@H]12
InChIKey: CYPNWLQSQPKVHJ-IIUIGEMCSA-N
Target: Proteinase-activated receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25116
Assay: FLIPR Assay: HEK 293 Cells were grown in media containing DMEM, 10% FBS pen/strep/L-Glutamine and non-essential amino acids. The cells were plated in 384-well PDL coated plates at 12000 cells/well and incubated overnight at 37° C./5% CO2. Media was then removed from the cells, which were then incubated with buffer (Hank's containing HEPES and Chaps) containing FLIPR calcium-5 dye, made with buffer containing probenecid, for 60 minutes at 37° C. Varying concentrations of compound in a final concentration of 5% DMSO were then added to the cells and incubated at 25° C. for 30 minutes. The plates were then added to the FLIPR Tetra and the device added a concentration of a PAR1 selective receptor-activating peptide with the sequence Ala-parafluoroPhe-Arg-Cha-Cit-Try-Nh2 (prepared in water) at a concentration equal to the effective concentration that achieves 80% activation of signaling on the day of the experiment.
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 521.61, ALogP 5.78, HBA 5, HBD 1, PSA 92.08, QED 0.5
Compound (SMILES): Cc1cc(-c2n[nH]c3ccc(C(=O)NC4CCCC(Cc5ccc(F)cc5)(C(=O)O)C4)cc23)ccn1
InChIKey: RCDXSOVHXHTGSW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P63085
Assay: Active ERK2 (aERK) Assay: Activated ERK2 activity was also determined in the IMAP assay format using the procedure outlined above. 1 μl of 25× compound was added to 14 μl of kinase buffer containing 0.25 ng fully phosphorylated, active Mouse ERK2 protein. Following a 30 minute incubation, the reactions were initiated by addition of 10 μl of kinase buffer containing 1 μM ERK2 IMAP substrate peptide (0.9 μM unlabeled IPTTPITTTYFFFK-CONH2 and 100 nM IPTTPITTTYFFFK(5-carboxyfluorescein)-CONH2) and 30 μM ATP. Reactions proceeded for 30 minutes before termination by addition of 60 μl IMAP detection beads in binding buffer. Plates were read as above after 30 minute binding equilibration. Active compounds were reconfirmed in an independent assay.
Measurement: IC50 = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 486.55, ALogP 5.06, HBA 4, HBD 3, PSA 107.97, QED 0.35
Compound (SMILES): CC(C)Oc1ccc(Nc2nc(=O)n(CCCOC3CCCCO3)c(=O)n2Cc2ccc(Cl)cc2)cc1F
InChIKey: PZPBYNVUKMXYIV-UHFFFAOYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Inhibition Assay: Stably expressing cell line (C6BU-1 cell transfected with human P2X3 receptor gene (GenBank accession number Y07683)) was used. The cells were seeded in a 96-well microtiter plate at a concentration of 8000 cells/well and cultured in the medium (8.3% fetal bovine serum, 8.3% horse serum, 1% antibiotic and antifungal in DMEM) for one day at 37 C. under 5% carbon dioxide atmosphere. The medium was replaced with 4 uM Fluo-3-AM solution (pH 7.5) containing 20 mM HEPES, 137 mM NaCl, 2.7 mM KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, 10% BSA, and 0.08% Pluronic F-127, and incubated at 37° C. under 5% dioxide carbon atmosphere for one hour. The plate was washed with washing buffer (20 mM HEPES, 137 mM NaCl, 2.7 mM KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, pH 7.5), and each well was added with 40 uL of this buffer. The plate was placed in High-Throughput Screening System FDSS 3000 (Hamamatsu Photonics K.K.).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 547.03, ALogP 4.71, HBA 9, HBD 1, PSA 96.61, QED 0.35
Compound (SMILES): COCc1nc2c(C(=O)Nc3ccc(C)cc3C)cc(NC(=O)c3ccccc3C(F)(F)F)cc2[nH]1
InChIKey: NRZVXQVHDYEQAA-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition Assay: mPGES-1 microsome fractions were prepared from CHO-K1 cells transiently transfected with plasmid encoding the human mPGES-1cDNA. Microsomes were diluted with potassium phosphate buffer containing reduced glutathione (pH7.4), and DMSO containing test compound or DMSO alone was added (such that DMSO final concentration would be 1% in each) and incubated at 4° C. for 20 minutes. Then, the enzymatic reactions were initiated by the addition of PGH2 substrate (final concentration 1 μM) and incubated at 4° C. for 60 seconds. The reaction was terminated by the addition of a citrate solution (final citrate concentration 50 mM) containing ferric chloride (final concentration 1 mg/mL). PGE2 production in the enzyme reaction aliquot was measured using HTRF kit (Cisbio International, catalogue #62P2APEC).
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 496.49, ALogP 5.85, HBA 4, HBD 3, PSA 96.11, QED 0.31