Orally Active Aminopeptidase A Inhibitor Prodrugs: Current State and Future Directions

AbstractPurpose of ReviewTo review the data supporting the use of aminopeptidase A (APA) inhibitor prodrugs as centrally acting antihypertensive agents.Recent FindingsBrain renin –angiotensin system (RAS) hyperactivity has been implicated in the development and maintenance of hypertension. Angiotensin III, generated by APA, one of the main effector peptides of the brain RAS, exerts a tonic stimulatory control over blood pressure in hypertensive rats. This identified brain APA as a potential therapeutic target for the treatment of hypertension, leading to the development of RB150/firibastat, an orally active prodrug of the specific and selective APA inhibitor, EC33. When given orally, RB150/firibastat 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.SummaryOrally active APA inhibitor prodrugs, by blocking brain RAS activity, represent promising novel strategy for treating hypertension.

Source: Current Hypertension Reports - May 20, 2019 Category: Primary Care Source Type: research