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

Mathilde Keck 1, 2, * Reda Hmazzou 1 Catherine Llorens-Cortes 1
* Corresponding author
1 Neuropeptides centraux et régulations hydrique et cardiovasculaire
UPMC - Université Pierre et Marie Curie - Paris 6, INSERM - Institut National de la Santé et de la Recherche Médicale : U691, CIRB - Centre interdisciplinaire de recherche en biologie
Abstract : PURPOSE OF REVIEW: To review the data supporting the use of aminopeptidase A (APA) inhibitor prodrugs as centrally acting antihypertensive agents. RECENT FINDINGS: Brain 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. Orally active APA inhibitor prodrugs, by blocking brain RAS activity, represent promising novel strategy for treating hypertension.
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https://www.hal.inserm.fr/inserm-02262448
Contributor : Mathilde Keck <>
Submitted on : Friday, August 2, 2019 - 3:10:46 PM
Last modification on : Wednesday, September 23, 2020 - 4:31:53 AM

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Mathilde Keck, Reda Hmazzou, Catherine Llorens-Cortes. Orally Active Aminopeptidase A Inhibitor Prodrugs: Current State and Future Directions. Current Hypertension Reports, Current Medicine Group, 2019, 21 (7), pp.50. ⟨10.1007/s11906-019-0957-4⟩. ⟨inserm-02262448⟩

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