Molidustat

Molidustat (BAY 85-3934) is an orally active small molecule inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH) with IC50 of 480 nM, 280 nM and 450 nM for PHD1, PHD2, and PHD3, respectively; causes dose-dependent production of erythropoietin (EPO) in healthy Wistar rats and cynomolgus monkeys, increases hemoglobin levels and shows effectivity in the treatment of renal anemia in rats with impaired kidney function, resultsin normalization of hypertensive blood pressure in rat model of CKD.Anemia Phase 3 Clinical (In Vitro) :The mean IC50 values of BAY 85-3934 for PHD1, PHD2, and PHD3 are 480 nM, 280 nM, and 450 nM, respectively. Exposure of HeLa cells to 5 μM BAY 85-3934 for 20 min is sufficient to induce detectable concentrations of HIF-1α. In a cellular reporter assay, BAY 85-3934 induces the expression of the firefly luciferase reporter gene under the control of a hypoxia responsive element promoter at a mean (± SD) EC50 of 8.4±0.7 μM (n=4) . (In Vivo) :HIF stabilization by oral administration of the HIF-PH inhibitor BAY 85-3934 (molidustat) results in dose-dependent production of EPO in healthy Wistar rats and cynomolgus monkeys. Molidustat therapy is aldo effective in the treatment of renal anemia in rats with impaired kidney function and, unlike treatment with rhEPO, resulted in normalization of hypertensive blood pressure in a rat model of CKD.