| First Author | Li Y | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 15 | Pages | e2122512119 |
| PubMed ID | 35380904 | Mgi Jnum | J:350353 |
| Mgi Id | MGI:7285882 | Doi | 10.1073/pnas.2122512119 |
| Citation | Li Y, et al. (2022) A screen of repurposed drugs identifies AMHR2/MISR2 agonists as potential contraceptives. Proc Natl Acad Sci U S A 119(15):e2122512119 |
| abstractText | We identified the anti-Mullerian hormone (also known as Mullerian inhibiting substance or MIS) as an inhibitory hormone that induces long-term contraception in mammals. The type II receptor to this hormone, AMHR2 (also known as MISR2), represents a promising druggable target for the modulation of female reproduction with a mechanism of action distinct from steroidal contraceptives. We designed an in vitro platform to screen and validate small molecules that can activate MISR2 signaling and suppress ovarian folliculogenesis. Using a bone morphogenesis protein (BMP)-response element luciferase reporter cell-based assay, we screened 5,440 compounds from a repurposed drug library. Positive hits in this screen were tested for specificity and potency in luciferase dose-response assays, and biological activity was tested in ex vivo Mullerian duct regression bioassays. Selected candidates were further evaluated in ex vivo follicle/ovary culture assays and in vivo in mice and rats. Here, we report that SP600125, CYC-116, gandotinib, and ruxolitinib can specifically inhibit primordial follicle activation and repress folliculogenesis by stimulating the MISR2 pathway. |
