Portal de Periódicos da CAPES

Rational design, synthesis and pharmacological characterization of novel aminopeptidase A inhibitors

2024; Elsevier BV; Volume: 113; Linguagem: Inglês

10.1016/j.bmcl.2024.129940

1464-3405

Fabrice Balavoine, Delphine Compère, Frédéric Miege, Nadia De Mota, Mathilde Keck, Mickael Fer, Aude Christen, Emmeline Martin, Didier Roche, Catherine Llorens‐Cortès, Vincent Rodeschini,

Renin-Angiotensin System Studies

Aminopeptidase A (APA) is a membrane-bound zinc metallopeptidase involved in the production of angiotensin III, one effector peptide of the brain renin-angiotensin system, making brain APA a relevant pharmacological target for the development of novel therapeutic treatments against hypertension and heart failure. The structure-based design of new APA inhibitors is described, based on previously developed thiol-containing inhibitors and APA crystal structure. Chemical synthesis, in vitro assessment against APA activity, pharmacological and pharmacokinetic profiling were performed, ultimately leading to a potent and selective APA inhibitor.