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.

roxadustat is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
We have been unable to find an ihibitory constant for roxadustat's inhibition of HIF-PHs (EGLN1-3). Associated patents examine stabilisation of HIF-1α or increased erythropoietin levels as markers of HIF-PH inhibition.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
egl-9 family hypoxia inducible factor 2 Hs Inhibitor Inhibition - - - 3
⤷ [3]
Targets where the ligand is described in the comment field
Target Comment
Zinc transporter 10 SLC30A10 mediates manganese excretion, and its expression is enhanced by manganese via an hypoxia-inducible factor (HIF)-regulated pathway [4]. The HIF-stabilising prolyl hydroxylase inhibitor roxadustat reduces manganese-induced neurotoxicity in vivo, which suggests that this mechanism may be a viable treatment option for neurological disease such as manganese-induced parkinsonism in humans.