MK-8617

Description: MK-8617 is a novel potent, selective, orally bioavailable pan-inhibitor of hypoxia-inducible factor prolyl hydroxylase 1?3 (HIF PHD1?3), which inhibits PHD1, 2, 3 with IC50 values of 1.0, 1.0 and 14 nM, respectively. MK-8617 is used for the treatment of anemia (10-19 hr dog and moneky t1/2). MK-8617 is not a significant inhibitor of the cytochrome p450 enzymes in vitro (IC50), CYP1A2, 3A4, 2B6, 2C9, 2C19, or 2D6, > 60 uM, and is a moderate reversible inhibitor of CYP2C8 at 1.6 uM in vitro. MK-8617 is potent, selective, orally bioavailable across several species, and active in stimulating erythropoiesis. Mouse and rat studies showed hematological changes with elevations of plasma EPO and circulating reticulocytes following single oral dose administration, while 4-week q.d. po administration in rat elevated hemoglobin levels. MK-8617 has advanced to human clinical trials for anemia.

References: J Med Chem. 2016 Dec 22; 59(24):11039-11049.