Development of the retinoic acid receptor alpha-specific antagonist YCT-529 for male contraception: A brief review

Genetic studies in mice have demonstrated that retinoic acid receptor alpha (RARα) deficiency leads to male infertility without affecting overall viability, suggesting that pharmacological inhibition of this receptor could be a viable contraceptive strategy. This review describes the use of experimental approaches to develop RARα-selective antagonists for male contraception. Initial studies with BMS-189453, a pan-RAR antagonist, showed significant testicular degeneration and reversible infertility in mice. The search for RARα-specific antagonists led to the development of YCT-529, a potent and selective RARα antagonist with favorable pharmacokinetics. YCT-529 demonstrated excellent in vivo efficacy in inhibiting spermatogenesis and inducing infertility in mice, with fertility recovery following drug discontinuation. YCT-529 is now in clinical development as a candidate for male contraception.