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Proc Natl Acad Sci U S A DOI:10.1073/pnas.2122512119

A screen of repurposed drugs identifies AMHR2/MISR2 agonists as potential contraceptives.

Publication TypeJournal Article
Year of Publication2022
AuthorsLi, YI, Wei, L, Meinsohn, M-C, Suliman, R, Chauvin, M, Berstler, J, Hartland, K, Jensen, MM, Sicher, NA, Nagykery, N, Donahoe, PK, Pépin, D
JournalProc Natl Acad Sci U S A
Volume119
Issue15
Pagese2122512119
Date Published2022 Apr 12
ISSN1091-6490
KeywordsAnimals, Anthracenes, Contraceptive Agents, Drug Evaluation, Preclinical, Drug Repositioning, Female, Humans, Mice, Nitriles, Ovarian Follicle, Pyrazoles, Pyrimidines, Rats, Receptors, Peptide, Receptors, Transforming Growth Factor beta, Small Molecule Libraries, Thiazoles
Abstract

SignificanceThis study aims to identify drugs that activate the Mullerian inhibiting substance pathway to be used for contraception or other applications in women's health. We describe a high-throughput screening pipeline to identify small molecules that activate the Mullerian inhibiting substance type 2 receptor (MISR2) and validate their activity in bioassays. We identify five compounds from a repurposed drug library that specifically induce MISR2 signaling, trigger regression of the Mullerian duct, and inhibit follicle activation. We test these compounds in vivo and show that they can repress folliculogenesis in mice and rats in an -dependent manner. These drugs may represent a class of ovarian regulators that inhibit preantral follicle activation and growth.

DOI10.1073/pnas.2122512119
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35380904?dopt=Abstract

Alternate JournalProc Natl Acad Sci U S A
PubMed ID35380904
Grant ListOPP1203044 / / Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) /