Efforts to develop both hormonal and nonhormonal birth control agents for men is underway for many years, but there is no approved drug yet. We have focused on many nonhormonal targets to circumvent the side effects associated with hormonal perturbation such as decreased libido, weight gain, mood changes, etc. RARα is a validated nonhormonal target for male contraception and we have already reported a selective RARα antagonist as a promising preclinical candidate. But Retinoic acid receptor gamma (RARγ), another member of the RAR family, was also shown to be essential for sperm production. So we designed and synthesized dual-selective RARα,γ antagonists to achieve the contraceptive effect at a lower dose. We utilized the structural difference between RARα,β, and γ to design antagonists that retain affinity for RARα and γ but loses affinity for RARβ. Few of the synthesized compounds showed potent antagonism of RARα and γ without much activity at RARβ. These compounds are being evaluated in vitro and in vivo pharmacokinetic studies.

Developing dual-selective RARα,γ antagonists as male birth control agents

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.