roxadustat [Ligand Id: 8454] activity data from GtoPdb and ChEMBL

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ChEMBL ligand: CHEMBL2338329 (ASP1517, ASP-1517, FG4592, FG-4592, Roxadustat)
  • Alpha-ketoglutarate-dependent dioxygenase FTO in Human [ChEMBL: CHEMBL2331065] [UniProtKB: Q9C0B1]
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  • egl-9 family hypoxia inducible factor 1/Egl nine homolog 1 in Human [ChEMBL: CHEMBL5697] [GtoPdb: 2833] [UniProtKB: Q9GZT9]
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  • Hypoxia-inducible factor 1-alpha inhibitor in Human [ChEMBL: CHEMBL5909] [UniProtKB: Q9NWT6]
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  • Prolyl 4-hydroxylase in Paramecium bursaria Chlorella virus 1 [ChEMBL: CHEMBL4523368] [UniProtKB: Q84406]
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DB Assay description Assay Type Standard value Standard parameter Original value Original units Original parameter Reference
Alpha-ketoglutarate-dependent dioxygenase FTO in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2331065] [UniProtKB: Q9C0B1]
ChEMBL Inhibition of human hexahistidine-tagged full-length FTO expressed in Escherichia coli BL21 (DE3) using 3-methylthymidine as substrate assessed as inhibition of 3-methylthymidine conversion to thymidine after 1 hr by liquid chromatographic analysis B 5.01 pIC50 9800 nM IC50 J. Med. Chem. (2013) 56: 3680-3688 [PMID:23547775]
egl-9 family hypoxia inducible factor 1/Egl nine homolog 1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5697] [GtoPdb: 2833] [UniProtKB: Q9GZT9]
ChEMBL Inhibition of HIF-PHD2 (181 to 426 residues) (unknown origin) using HIF1-alpha (556 to 574 residues) as substrate in presence of 2-OG preincubated for 30 mins followed by OPD addition measured after 10 mins by fluorescence assay B 5.24 pIC50 5740 nM IC50 J Med Chem (2018) 61: 5332-5349 [PMID:29856623]
ChEMBL HIF-PH Assay: Ketoglutaric acid alpha -[1-14C]-sodium salt, alpha-ketoglutaric acid sodium salt, and HPLC purified peptide were obtained from commercial sources, e.g., Perkin-Elmer (Wellesley Mass.), Sigma-Aldrich, and SynPep Corp. (Dublin Calif.), respectively. Peptides for use in the assay were fragments of HIFalpha as described above or as disclosed in International Publication WO 2005/118836, incorporated by reference herein. For example, a HIF peptide for use in the HIF-PH assay was [methoxycoumarin]-DLDLEALAPYIPADDDFQL-amide. HIF-PH, e.g., HIF-PH2 (also known as EGLN1 or PHD2), was expressed in, e.g., insect Hi5 cells, and partially purified, e.g., through a SP ion exchange chromatography column. Enzyme activity was determined by capturing 14CO2 using an assay described by Kivirikko and Myllyla (1982, Methods Enzymol. 82:245-304). Assay reactions contained 50 mM HEPES (pH 7.4), 100 uM alpha -ketoglutaric acid sodium salt, 0.30 uCi/mL alpha -ketoglutaric acid alpha -[1-14C]-sodium. B 5.68 pIC50 2100 nM IC50 US-9115085-B2. Crystalline forms of a prolyl hydroxylase inhibitor (2015)
ChEMBL HIF-PH Assay: Ketoglutaric acid α-[1-14C]-sodium salt, alpha-ketoglutaric acid sodium salt, and HPLC purified peptide were obtained from commercial sources, e.g., Perkin-Elmer (Wellesley Mass.), Sigma-Aldrich, and SynPep Corp. (Dublin Calif.), respectively. Peptides for use in the assay were fragments of HIFα as described above or as disclosed in International Publication WO 2005/118836, incorporated by reference herein. For example, a HIF peptide for use in the HIF-PH assay was [methoxycoumarin]-DLDLEALAPYIPADDDFQL-amide. HIF-PH, e.g., HIF-PH2 (also known as EGLN1 or PHD2), was expressed in, e.g., insect Hi5 cells, and partially purified, e.g., through a SP ion exchange chromatography column. Enzyme activity was determined by capturing 14CO2 using an assay described by Kivirikko and Myllyla (1982, Methods Enzymol. 82:245-304). Assay reactions contained 50 mM HEPES (pH 7.4), 100 μM α-ketoglutaric acid sodium salt, 0.30 μCi/mL α-ketoglutaric acid α-[1-14C]-sodium salt, 40 μM FeSO4, 1 mM ascorbate, 1541.8 units/mL Catalase, with or without 50 μM peptide substrate and various concentrations of compound of the invention. Reactions were initiated by addition of HIF-PH enzyme. B 5.68 pIC50 2100 nM IC50 US-9340511-B2. Process for making isoquinoline compounds (2016)
ChEMBL Displacement of FITC-HIF-1alpha (556 to 574 residues) from PHD2 (181 to 426 residues) (unknown origin) after 60 mins by fluorescence polarization assay B 6.23 pIC50 591.4 nM IC50 ACS Med. Chem. Lett. (2015) 6: 1236-1240 [PMID:26713111]
ChEMBL Inhibition of HIF-PHD2 (181 to 426 residues) (unknown origin) using FITC-HIF1-alpha (556 to 574 residues) as substrate after 60 mins by fluorescence polarization assay B 6.23 pIC50 591.4 nM IC50 J Med Chem (2018) 61: 5332-5349 [PMID:29856623]
ChEMBL Inhibition of FITC-HIF1alpha (556 to 574 residues) binding to PHD2 (181 to 426 residues) (unknown origin) by fluorescence polarization assay B 6.23 pIC50 591 nM IC50 J Med Chem (2020) 63: 10045-10060 [PMID:32787144]
ChEMBL Inhibition of PHD2 (181 to 426 residues) (unknown origin) using FITC-HIF1alpha (556 to 574 residues) as substrate after 60 mins by fluorescence polarization assay B 6.24 pIC50 575.3 nM IC50 J Med Chem (2019) 62: 7583-7588 [PMID:31244107]
ChEMBL Inhibition of HIF-PHD2 (unknown origin) B 7.49 pIC50 32 nM IC50 J Med Chem (2016) 59: 11039-11049 [PMID:28002958]
ChEMBL Inhibition of recombinant human PHD2 using 2OG as substrate and Fe2 as co-factor assessed as hydroxylation incubated for 15 mins in presence of L-ascorbate by LC-MS analysis B 7.57 pIC50 27 nM IC50 Bioorg Med Chem (2019) 27: 2405-2412 [PMID:30737136]
Hypoxia-inducible factor 1-alpha inhibitor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5909] [UniProtKB: Q9NWT6]
ChEMBL Inhibition of recombinant human FIH using 2OG as substrate and Fe2 as co-factor assessed as hydroxylation incubated for 15 mins in presence of L-ascorbate by LC-MS analysis B 4 pIC50 >100000 nM IC50 Bioorg Med Chem (2019) 27: 2405-2412 [PMID:30737136]
Prolyl 3-hydroxylase OGFOD1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4523398] [UniProtKB: Q8N543]
ChEMBL Inhibition of recombinant human OGFOD1 using 2OG as substrate and Fe2 as co-factor assessed as hydroxylation incubated for 15 mins in presence of L-ascorbate by MALDI-TOF MS analysis B 6 pIC50 <1000 nM IC50 Bioorg Med Chem (2019) 27: 2405-2412 [PMID:30737136]
Prolyl 4-hydroxylase in Paramecium bursaria Chlorella virus 1 (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4523368] [UniProtKB: Q84406]
ChEMBL Inhibition of N-terminal His6-tagged recombinant Paramecium bursaria chlorella virus 1 CPH expressed in Escherichia coli Rosetta 2 (DE3) cells pre-incubated for 5 mins before 2OG as substrate and Fe2 as co-factor addition in presence of L-ascorbate and measured after 5 mins MALDI TOF MS analysis B 5.97 pKi 1070 nM Ki Bioorg Med Chem (2019) 27: 2405-2412 [PMID:30737136]
ChEMBL Inhibition of N-terminal His6-tagged recombinant Paramecium bursaria chlorella virus 1 CPH expressed in Escherichia coli Rosetta 2 (DE3) cells pre-incubated for 5 mins before 2OG as substrate and Fe2 as co-factor addition in presence of L-ascorbate and measured after 5 mins MALDI TOF MS analysis B 5.3 pIC50 5000 nM IC50 Bioorg Med Chem (2019) 27: 2405-2412 [PMID:30737136]

ChEMBL data shown on this page come from version 31:

Gaulton A, Hersey A, Nowotka M, Bento AP, Chambers J, Mendez D, Mutowo P, Atkinson F, Bellis LJ, Cibrián-Uhalte E, Davies M, Dedman N, Karlsson A, Magariños MP, Overington JP, Papadatos G, Smit I, Leach AR. (2017) 'The ChEMBL database in 2017.' Nucleic Acids Res., 45(D1). DOI: 10.1093/nar/gkw1074. [PMCID:5210557]