Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 15:113:129940.
doi: 10.1016/j.bmcl.2024.129940. Epub 2024 Sep 2.

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

Fabrice Balavoine  1 , Delphine Compere  2 , Frédéric Miege  3 , Nadia De Mota  4 , Mathilde Keck  2 , Mickael Fer  3 , Aude Christen  3 , Emmeline Martin  3 , Didier Roche  3 , Catherine Llorens-Cortes  5 , Vincent Rodeschini  6
Affiliations

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

Fabrice Balavoine et al. Bioorg Med Chem Lett. .

Abstract

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.

Keywords: Aminopeptidase A; Aminophosphinic acid; Metalloprotease inhibitor; Renin-angiotensin system; Structure-activity relationships.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fabrice Balavoine has patent issued to Assignee. Delphine Compere has patent issued to Assignee. Catherine Llorens-Cortes has patent issued to Assignee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

LinkOut - more resources