HIF prolyl-hydroxylase inhibitor

Not to be confused with Factor Inhibiting HIF Asparaginyl Hydroxylase Inhibitors

HIF prolyl-hydroxylase inhibitor
Drug class
Roxadustat, the first marketed HIF prolyl-hydroxylase inhibitor
Class identifiers
ATC codeB03X
Mechanism of actionEnzyme inhibitor
Biological targetHIF prolyl-hydroxylase
In Wikidata


Hypoxia-inducible factor prolyl hydroxylase Inhibitors (HIF-PHIs) also known as hypoxia-inducible factor stabilizers (HIF stabilizers) are members of a mostly experimental class of drugs that act by inhibiting hypoxia-inducible factor-proline dioxygenase (HIF prolyl-hydroxylase) which is responsible to break down the hypoxia-inducible factor (HIF) under conditions of normal oxygen concentrations.

As of 2008 they had been investigated in in cell models for the treatment of anemia, chronic kidney disease (CKD), ischemia[1] including ischemia of the heart tissue,[2] cancer,[3] and others.[4] Research conducted in mice suggests that they may increase hippocampal memory by increasing erythropoietin expression.[5]

As of 2021 research focuses mainly on anemia associated with CKD, and to some extent on ischemia.[6][7] One drug of this class (roxadustat) is marketed in China and Japan for the treatment of anaemia in CKD patients.[8][9]

Examples

See also
  • Hypoxia-inducible factors#As a therapeutic target

References
  1. Warnecke, C.; Griethe, W.; Weidemann, A.; Jurgensen, J. S.; Willam, C.; Bachmann, S.; Ivashchenko, Y.; Wagner, I.; Frei, U.; Wiesener, M.; Eckardt, K.-U. (2003). "Activation of the hypoxia-inducible factor pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors". The FASEB Journal. 17 (9): 1186–8. doi:10.1096/fj.02-1062fje. PMID 12709400. S2CID 45194703.
  2. Nangaku, M.; Izuhara, Y.; Takizawa, S.; Yamashita, T.; Fujii-Kuriyama, Y.; Ohneda, O.; Yamamoto, M.; Van Ypersele De Strihou, C.; et al. (2007). "A Novel Class of Prolyl Hydroxylase Inhibitors Induces Angiogenesis and Exerts Organ Protection Against Ischemia". Arteriosclerosis, Thrombosis, and Vascular Biology. 27 (12): 2548–2554. doi:10.1161/ATVBAHA.107.148551. PMID 17932321.
  3. Ivan, Mircea (2006). "HIF-PROLYL hydroxylase inhibitors: From basic science to clinical trials" (PDF). MÆDICA - a Journal of Clinical Medicine. 1 (2): 67–69. ISSN 1841-9038.
  4. "FibroGen Reports New Research on Development of HIF Prolyl Hydroxylase Inhibitors Related to Endothelial Progenitor Cells, Anti-Inflammation, Cytoprotection and Erythropoiesis". drugs.com. 2008.
  5. Adamcio, B; Sperling, S; Hagemeyer, N; Walkinshaw, G; Ehrenreich, H (2010). "Hypoxia inducible factor stabilization leads to lasting improvement of hippocampal memory in healthy mice". Behavioural Brain Research. 208 (1): 80–4. doi:10.1016/j.bbr.2009.11.010. PMID 19900484. S2CID 20395457.
  6. "HIF prolyl-hydroxylase inhibitors on PubMed". National Library of Medicine. Retrieved 2021-03-08.
  7. "HIF prolyl-hydroxylase inhibitors on ClinicalTrials.gov". National Library of Medicine. Retrieved 2021-03-08.
  8. Dhillon, Sohita (2019). "Roxadustat: First Global Approval". Drugs. 79 (5): 563–572. doi:10.1007/s40265-019-01077-1. PMID 30805897. S2CID 71147333.
  9. "Astellas Receives Approval of Evrenzo (roxadustat) in Japan for the Treatment of Anemia of Chronic Kidney Disease in Adult Patients Not on Dialysis". Astellas. 2020-11-27.


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