Syracuse

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

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Balavoine, Fabrice | Compere, Delphine | Miege, Frédéric | de Mota, Nadia | Keck, Mathilde | Fer, Mickael | Christen, Aude | Martin, Emmeline | Roche, Didier | Llorens-Cortes, Catherine | Rodeschini, Vincent

Edité par CCSD ; Elsevier -

International audience. 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.

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