Osilodrostat is an inhibitor of aldosterone synthase (IC50 = 0.7 nM for the recombinant human enzyme).1 It is selective for human aldosterone synthase over rat aldosterone synthase (IC50 = 160 nM). Osilodrostat inhibits increases in plasma aldosterone levels induced by angiotensin II or adrenocorticotropic hormone (ACTH) in rats (ED50s = 0.6 and 1.1 mg/kg, respectively). It reduces mean arterial pressure and prolongs survival in rats expressing human renin and angiotensinogen, a double-transgenic model of angiotensin II-dependent hypertension, in a dose-dependent manner. Formulations containing osilodrostat have been used in the treatment of Cushing’s syndrome.
1.Ménard, J., Rigel, D.F., Watson, C., et al.Aldosterone synthase inhibition: Cardiorenal protection in animal disease models and translation of hormonal effects to human subjectsJ. Transl. Med.12340(2014)