Abstract:
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.
