Desidustat is an inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH).1 It reduces levels of hypoxia-inducible factor-1α (HIF-1α), a transcription factor regulated by HIF-PH enzymes, in rat liver and kidney. Desidustat increases the expression of the red blood cell- and iron transport-related genes Epo, Fpn1, and Hamp in rat liver in a model of anemia induced by peptidoglycan-polysaccharide (PGPS).2 It increases plasma levels of erythropoietin in rats by 10.3- to 40-fold when administered at doses of 15 and 30 mg/kg, respectively.1 Desidustat (15 and 30 mg/kg) also increases plasma levels of erythropoietin and hemoglobin, as well as the number of circulating red blood cells, in nephrectomized rats in a model of chronic kidney disease-induced anemia. It increases hemoglobin levels and the number of circulating red blood cells in a mouse model of anemia induced by the DNA-crosslinking agent cisplatin .
1.Jain, M.R., Joharapurkar, A.A., Pandya, V., et al.Pharmacological characterization of ZYAN1, a novel prolyl hydroxylase inhibitor for the treatment of anemiaDrug Res. (Stuttg.)66(2)107-112(2016) 2.Jain, M., Joharapurkar, A., Patel, V., et al.Pharmacological inhibition of prolyl hydroxylase protects against inflammation-induced anemia via efficient erythropoiesis and hepcidin downregulationEur. J. Pharmacol.843113-120(2019)