ODM-208 (Opevesostat) is a potent, selective, orally bioavailable CYP11A1 inhibitor, inhibits the biosynthesis of pregnenolone with IC50 of 15 nM in NCI-H295R cells.
ODM-208 is CYP11A1-selective, shows >1,000 selectivity over metabolising CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4).
ODM-208 is superior in steroid hormone biosynthesis inhibition compared to the non-selective CYP inhibitors ketoconazole and etomidate.
ODM-208 displays pregnenolone production inhibition with IC50 of 108 nM and 2,167 nM with NADPH and without NADPH, respectively.
ODM-208 displays rapid, complete, durable, and reversible inhibition of the steroid hormone biosynthesis in an adrenocortical carcinoma cell model in vitro, in adult non-castrated male mice and dogs, and in patients with CRPC.
ODM-208 (2 mg/kg/day, oral) treatment causes a significant and dose-dependent decrease in the plasma cortisol and testosterone concentrations in adult non-castrated Beagle dogs.