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The importance of this ligand-receptor pair in the development of the gubernacular ligament during the transabdominal phase of testicular descent is well established. More recently, RXFP2 has been implicated in maintaining healthy bone formation. In this report, we describe the discovery of a small molecule series of RXFP2 agonists. These compounds are highly potent, efficacious, and selective RXFP2 allosteric agonists that induce gubernacular invagination in mouse embryos, increase mineralization activity in human osteoblasts in vitro, and improve bone trabecular parameters in adult mice. The described RXFP2 agonists are orally bioavailable and display favorable pharmacokinetic properties, which allow for future evaluation of the therapeutic benefits of modulating RXFP2 activation in disease models.<\/jats:p>","DOI":"10.1038\/s42003-022-04143-9","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T16:04:58Z","timestamp":1667577898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovery of small molecule agonists of the Relaxin Family Peptide Receptor 2"],"prefix":"10.1038","volume":"5","author":[{"given":"Maria","family":"Esteban-Lopez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth J.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney","family":"Myhr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena M.","family":"Kaftanovskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-880X","authenticated-orcid":false,"given":"Noel T.","family":"Southall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Barnaeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmett R.","family":"George","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-5364","authenticated-orcid":false,"given":"John T.","family":"Sherrill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Morello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-0324","authenticated-orcid":false,"given":"Irina U.","family":"Agoulnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-7061","authenticated-orcid":false,"given":"Juan J.","family":"Marugan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6845","authenticated-orcid":false,"given":"Alexander I.","family":"Agoulnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"4143_CR1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1093\/molehr\/3.6.459","volume":"3","author":"R Ivell","year":"1997","unstructured":"Ivell, R. et al. 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