roxadustat [Ligand Id: 8454] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL2338329 (ASP-1517, ASP1517, Evrenzo, FG-4592, FG4592, Roxadustat) |
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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 PHD2 (unknown origin) measured by fluorescence polarization assay | B | 6.28 | pIC50 | 520 | nM | IC50 | Eur J Med Chem (2022) 230: 114115-114115 [PMID:35033824] |
| ChEMBL | Inhibition of PHD2 (181 to 426 residue) (unknown origin) measured by fluorescence polarization assay | B | 6.92 | pIC50 | 120.5 | nM | IC50 | Eur J Med Chem (2022) 238: 114479-114479 [PMID:35675755] |
| ChEMBL | Inhibition of PHD2 (unknown origin) incubated for 15 mins by competitive fluorescence polarization assay | B | 7.33 | pIC50 | 47 | nM | IC50 | J Med Chem (2022) 65: 7193-7211 [PMID:35507418] |
| 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] |
| ChEMBL | Inhibition of PHD2 in human Hep3B cells assessed as increase in EPO production measured after 24 hrs by ELISA | B | 5.21 | pEC50 | 6110 | nM | EC50 | Bioorg Med Chem Lett (2022) 76: 129007-129007 [PMID:36174835] |
| 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] |
| Thyroid hormone receptor-α/Thyroid hormone receptor alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1860] [GtoPdb: 588] [UniProtKB: P10827] | ||||||||
| ChEMBL | Agonist activity at wild type human TR alpha LBD expressed in Escherichia coli BL21 (DE3) assessed as induction of N-terminal biotinylated coactivator SRC2-3 peptide recruitment by alphascreen assay | B | 7.49 | pEC50 | 32.7 | nM | EC50 | J Med Chem (2022) 65: 7193-7211 [PMID:35507418] |
| Thyroid hormone receptor-β/Thyroid hormone receptor beta-1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1947] [GtoPdb: 589] [UniProtKB: P10828] | ||||||||
| ChEMBL | Agonist activity at human TR beta LBD (202 to 461 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as induction of N-terminal biotinylated coactivator SRC2-3 peptide recruitment by alphascreen assay | B | 7.89 | pEC50 | 12.9 | nM | EC50 | J Med Chem (2022) 65: 7193-7211 [PMID:35507418] |
ChEMBL data shown on this page come from version 34:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]
