MK-8617 is an orally active pan-inhibitor of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) with an IC₅₀ of 1 nM for PHD2. IC50 & Target: IC50: 1 nM (PHD2)^[1] In Vitro: MK-8617 is an orally active pan-inhibitor of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) with an IC₅₀ of 1 nM for PHD2. MK-8617 is not a significant inhibitor of the cytochrome p450 enzymes in vitro (IC₅₀), CYP1A2, 3A4, 2B6, 2C9, 2C19, or 2D6, >60 μM, and is a moderate reversible inhibitor of CYP2C8 at 1.6 μM in vitro. The IC₅₀ of MK-8617 is determined for factor inhibiting HIF (FIH) to be 18 μM^[1]. In Vivo: Tritiated MK-8617 exhibits minimal metabolic turnover in liver microsomes from rat, dog, and monkey (<10% turover) but significant turnover in human liver microsomes (34% turnover) after 60 min (10 μM MK-8617, 1 mg/mL microsomal protein). In terms of its pharmacokinetic profile, MK-8617 shows good oral bioavailability across species (36 to 71%), with low clearance and volume of distribution. After 48 h treatment of MK-8617, postdose recovery of the radioactivity is about 26% bile, 12% urine, and 38% in feces, indicating that ~38% of the MK-8617 is absorbed and eliminated into bile and urine which is consistent with the oral bioavailability (~36%) observed in the rat study. MK-8617 also elicits an increase in erythropoietin (EPO) levels with a mouse MED of 1.5 mpk when dosed iv^[1].