Cargando…

Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists

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 modifie...

Descripción completa

Detalles Bibliográficos
Autores principales: Anderson, Ross C., Newton, Claire L., Millar, Robert P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352558/
https://www.ncbi.nlm.nih.gov/pubmed/30728807
http://dx.doi.org/10.3389/fendo.2018.00757
_version_ 1783390858735779840
author Anderson, Ross C.
Newton, Claire L.
Millar, Robert P.
author_facet Anderson, Ross C.
Newton, Claire L.
Millar, Robert P.
author_sort Anderson, Ross C.
collection PubMed
description 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 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 the FSHR in diverse extragonadal tissues, including 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.
format Online
Article
Text
id pubmed-6352558
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-63525582019-02-06 Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists Anderson, Ross C. Newton, Claire L. Millar, Robert P. Front Endocrinol (Lausanne) Endocrinology 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 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 the FSHR in diverse extragonadal tissues, including 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. Frontiers Media S.A. 2019-01-23 /pmc/articles/PMC6352558/ /pubmed/30728807 http://dx.doi.org/10.3389/fendo.2018.00757 Text en Copyright © 2019 Anderson, Newton and Millar. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Endocrinology
Anderson, Ross C.
Newton, Claire L.
Millar, Robert P.
Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists
title Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists
title_full Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists
title_fullStr Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists
title_full_unstemmed Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists
title_short Small Molecule Follicle-Stimulating Hormone Receptor Agonists and Antagonists
title_sort small molecule follicle-stimulating hormone receptor agonists and antagonists
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352558/
https://www.ncbi.nlm.nih.gov/pubmed/30728807
http://dx.doi.org/10.3389/fendo.2018.00757
work_keys_str_mv AT andersonrossc smallmoleculefolliclestimulatinghormonereceptoragonistsandantagonists
AT newtonclairel smallmoleculefolliclestimulatinghormonereceptoragonistsandantagonists
AT millarrobertp smallmoleculefolliclestimulatinghormonereceptoragonistsandantagonists