Small molecule follicle-stimulating hormone receptor agonists and antagonists
- 1Centre for Neuroendocrinology and Department of Physiology, University of Pretoria, South Africa
The follicle-stimulating hormone receptor (FSHR) has been targeted therapeutically for decades, due to its pivotal role in reproduction. To date, only purified and recombinant/biosimilar FSH have been used to target FSHR in assisted reproduction, with the exception of corifollitropin alfa; a modified gonadotropin in which the FSH beta subunit is joined to the C-terminal peptide of the human choriogonadotropin beta subunit, to extend serum half-life. Assisted reproduction protocols usually entail the trauma of multiple painful injections of FSH to initiate and promote folliculogenesis, which has prompted the development of a number of orally-available low molecular weight (LMW) chemical scaffolds targeting the FSHR. Furthermore, the recently documented roles of FSHR in diverse extragonadal tissues and conditions, such as cancer, fat metabolism and bone density regulation, has highlighted the potential utility of LMW modulators of FSHR activity. Despite these chemical scaffolds encompassing a spectrum of in vitro and in vivo activities and pharmacological profiles, none have yet reached the clinic. In this review we discuss the major chemical classes of LMW molecules targeting the FSHR, and document their activity profiles and current status of development, in addition to discussing potential clinical applications.
Keywords: Follicle-stimulating hormone (FSH / FSH receptor), agonists, antagonists, Small-molecule, GPCR (G-protein-coupled receptors), Assisted reproduction (ART)
Received: 30 Sep 2018;
Accepted: 29 Nov 2018.
Edited by:Ilpo Huhtaniemi, Imperial College London, United Kingdom
Reviewed by:Aylin C. Hanyaloglu, Imperial College London, United Kingdom
Livio Casarini, Università degli Studi di Modena e Reggio Emilia, Italy
James A. Dias, School of Public Health, University at Albany, United States
Copyright: © 2018 Anderson, Newton and Millar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Ross C. Anderson, University of Pretoria, Centre for Neuroendocrinology and Department of Physiology, Pretoria, South Africa, email@example.com