Firibastat (QGC001), an orally active brain penetrating prodrug of EC33, is a first-in-class brain aminopeptidase A (APA) inhibitor (Ki=200 nM). Firibastat selectively and specifically inhibits conversion of brain angiotensin-II into angiotensin-III and decreases blood pressure in hypertensive rats[1][2].
When given orally, Firibastat (0.1-30 mg/kg; p.o.) crosses the gastrointestinal and blood-brain barriers, enters the brain, and generates two active molecules of EC33 which inhibit brain APA activity, blocking brain angiotensin III formation, and decrease blood pressure for several hours in hypertensive rats[2].
[1]. Ferdinand KC, et al. Efficacy and Safety of Firibastat, A First-in-Class Brain Aminopeptidase A Inhibitor, in Hypertensive Overweight Patients of Multiple Ethnic Origins. Circulation. 2019;140(2):138-146.
[2]. Keck M, et al. Orally Active Aminopeptidase A Inhibitor Prodrugs: Current State and Future Directions. Curr Hypertens Rep. 2019;21(7):50. Published 2019 May 21.