I was curious about the mechanism.
https://www.nature.com/articles/s43856-025-00752-7
> YCT-529 works by interfering with vitamin A signaling necessary for sperm production and fertility.
> The importance of dietary vitamin A and retinoid signaling for male germ cell development and differentiation has been recognized for many years6. All trans-retinoic acid (Fig. 1a) is an active metabolite of vitamin A that exerts its function, at least partly, by binding to retinoic acid receptors (RARs). The RARs α, β, and γ, are encoded by the Rara, Rarb, and Rarg genes in mice, and Rarα and Rarγ have been validated as contraceptive targets by genetic knockouts resulting in male sterility7,8. Notably, the effects on spermatogenesis in the absence of RARα most resemble the loss of RAR signaling in vitamin A deficiency, and the mice are otherwise normal7,8. Further, the effects on spermatogenesis in animals treated orally with the dual RARα/RARγ antagonist BMS-189453 (Fig. 1a, b) closely phenocopied the absence of RARα function. Importantly, the resulting male sterility is reversible9,10,11. We, therefore, wished to identify RARα−selective inhibitors for potential male non-hormonal contraception. Our study describes the development of YCT-529, a highly selective RARα antagonist that reduces sperm counts in mice and non-human primates. Mating studies with male mice treated with 10 mg/kg/day for 4 weeks show that YCT-529 is 99% effective in preventing pregnancies and that the mice fully regain fertility after drug cessation.
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