roxadustat   Click here for help

GtoPdb Ligand ID: 8454

Synonyms: ASP-1517 | ASP1517 | Evrenzo® | FG-4592 | FG4592
Approved drug PDB Ligand
roxadustat is an approved drug (EMA (2021))
Compound class: Synthetic organic
Comment: Roxadustat is a compound which inhibits hypoxia inducible factor prolyl hydroxylase (HIF-PH) activity. HIF-PH inhibitors are being investigated as novel therapies for anemia, especially anemia caused by chronic kindney disease (CKD) [2]. It is hoped that HIF-PH inhibitors will provide a more effective alternative to the use of erythropoetin replacement therapy plus iron supplementation in CKD patients.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 108.75
Molecular weight 352.11
XLogP 0.99
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OC(=O)CNC(=O)c1nc(C)c2c(c1O)ccc(c2)Oc1ccccc1
Isomeric SMILES OC(=O)CNC(=O)c1nc(C)c2c(c1O)ccc(c2)Oc1ccccc1
InChI InChI=1S/C19H16N2O5/c1-11-15-9-13(26-12-5-3-2-4-6-12)7-8-14(15)18(24)17(21-11)19(25)20-10-16(22)23/h2-9,24H,10H2,1H3,(H,20,25)(H,22,23)
InChI Key YOZBGTLTNGAVFU-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Roxadustat was the first HIF-PH inhibitor to reach Phase 3 clinical trial. Click here to link to ClinicalTrials.gov's listing of registered Phase 3 roxadustat trials.
The EMA approved roxadustat for the treatment of anemia due to chronic kidney failure in August 2021.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Under normoxic conditions HIF-PH effects the degradation of HIF1-α subunits (using O2 as a substrate to hydroxylate proline residues in HIF-1α), resulting in minimal HIF-induced transcriptional activity. When oxygen levels are limited, HIF-1α is not directed for degradation, permittinh induction of transcription. HIF-PH inhibitors mimic this natural response to hypoxia, which stablises HIFα transcription factors thereby switching on transcription of genes associated with processes such as erythropoiesis and vasculogenesis [2]. In anemic patients HIF-PH inhibitors increase erythropoietin levels and subsequently increase red blood cell counts [1]. There are three human HIF-PHs, with gene symbols EGLN1, -2 and -3.