Retinoic acid receptor alpha (RARA), a nuclear receptor protein, has been validated as a target for male contraception by gene knockout studies and also pharmacologically using a pan-retinoic acid receptor antagonist. Retinoic acid receptor alpha activity is indispensable for the spermatogenic process, and therefore its antagonists have potential as male contraceptive agents. This review discusses the effects of systematic dosing regimen modifications of the orally bioavailable and reversible pan-antagonist BMS-189453 as well as studies with the alpha-selective antagonists BMS-189532 and BMS-189614 in a murine model. We also provide an overview of structure–activity studies of retinoic acid receptor alpha antagonists that provide insight for the design of novel alpha-selective ligands.

中文翻译：

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用于男性避孕的视黄酸受体拮抗剂：现状†。

视黄酸受体α (RARA) 是一种核受体蛋白，通过基因敲除研究和泛视黄酸受体拮抗剂的药理学研究，已被验证为男性避孕的靶标。视黄酸受体α活性对于生精过程是不可或缺的，因此其拮抗剂具有作为男性避孕药的潜力。本综述讨论了口服生物利用度和可逆性泛拮抗剂BMS-189453的系统给药方案修改的影响，以及在小鼠模型中使用 α 选择性拮抗剂BMS-189532和BMS-189614进行的研究。我们还概述了视黄酸受体α拮抗剂的结构活性研究，为新型α选择性配体的设计提供了见解。