Daprodustat is a small-molecule hypoxia-inducible factor prolyl hydroxylase inhibitor used for the treatment of anemia in patients with chronic kidney disease. Patients with CKD cannot induce erythropoietin (EPO) production in response to hypoxia or anemia.
- Mechanism
- Curator reviewed · 9 references
Chronic kidney disease (CKD) is associated with several complications, including anemia. The development of anemia in patients with CKD is mostly due to the kidneys' inability to produce a sufficient amount of erythropoietin (EPO). Daprodustat is a potent reversible inhibitor of hypoxia-inducible factor (HIF)-prolyl hydroxylase (PH) 1, PH2 and PH3, with an IC50 in the low nM range. By inhibiting HIF-PHDs, daprodustat promotes the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors. HIF-α translocates to the nucleus and binds to hypoxia response elements (HREs) on DNA to promote the production of EPO as well as proteins involved in iron uptake, mobilization, and transport. Ultimately, erythropoiesis is increased, iron transport is upregulated, and circulating Hb levels are elevated.
- Primary indication
- Daprodustat is a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor indicated for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least four months.Curator reviewed · 1 structured indication
- Formula / weight
- C19H27N3O6 · 393.44 g/mol (avg)
- First approval
- United States, 2023
- Code names
- GSK-1278863
- Brand names
Resolves to
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Which drugs share a target with Daprodustat, and which of those have an active Phase 3 trial?
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