molidustat   Click here for help

GtoPdb Ligand ID: 8456

Synonyms: BAY 85-3934 | BAY-853934 | BAY85-3934
PDB Ligand
Compound class: Synthetic organic
Comment: Molidustat 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). 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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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 105.71
Molecular weight 314.12
XLogP 0.32
No. Lipinski's rules broken 0
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Canonical SMILES O=c1n([nH]cc1n1ccnn1)c1ncnc(c1)N1CCOCC1
Isomeric SMILES O=c1n([nH]cc1n1ccnn1)c1ncnc(c1)N1CCOCC1
InChI InChI=1S/C13H14N8O2/c22-13-10(20-2-1-16-18-20)8-17-21(13)12-7-11(14-9-15-12)19-3-5-23-6-4-19/h1-2,7-9,17H,3-6H2
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Summary of Clinical Use Click here for help
Molidustat (BAY85-3934) has reached Phase 2 clinical trial evaluating its potential as a therapy for treating anemia associated with chronic renal insufficiency against current therapies such as darbepoetin alfa and epoetin alfa/beta (recombinant erythropoietins).
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.