Ligand id: 8455

Name: daprodustat

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 124.09
Molecular weight 393.19
XLogP 1.68
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
daprodustat (GSK1278863) has reached Phase II clinical trial in both hemodialysis-dependent and non-dialysis dependent patient groups. Separate Phase II trials investigating GSK1278863's ability to reduce ischemic events in patients undergoing thoracic aortic aneurysm repair and evaluating any clinical benefit in patients with peripheral vascular disease (where tissue hypoxia is an issue) are also registered with ClinicalTrials.gov.
Mechanism Of Action and Pharmacodynamic Effects
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.