Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware St. SE, Minneapolis, MN 55414, United States.
Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware St. SE, Minneapolis, MN 55414, United States.
Bioorg Med Chem Lett. 2020 Mar 15;30(6):126958. doi: 10.1016/j.bmcl.2020.126958. Epub 2020 Jan 21.
While many contraception options are available for women, birth control methods for men are limited to condoms and vasectomy. Past research into male contraceptives has focused on hormonal options but the associated side effects have thus far precluded this method from reaching the market. Non-hormonal male contraceptives and vas occlusion have also been explored, but to date no method has progressed past clinical testing. Recent interest in epigenetic research has unveiled a new potential non-hormonal male contraceptive target: the testis-specific bromodomain BRDT. Potent inhibitors for bromodomain-containing proteins are described in the literature, but a BRDT-specific compound has yet to be designed, prepared and tested. The high similarity between bromodomain proteins of the BET family makes development of selective and specific inhibitors both difficult and necessary. Selective inhibition of BRDT by a small molecule is an exciting new target in the search for a new non-hormonal male contraceptive.
虽然有许多避孕选择可供女性使用，但男性的避孕方法仅限于避孕套和输精管切除术。过去对男性避孕药的研究集中在激素选择上，但相关的副作用迄今为止使这种方法无法进入市场。非激素男性避孕药和输精管闭塞也已经被探索过，但迄今为止没有一种方法能够通过临床测试。最近对表观遗传学研究的兴趣揭示了一种新的潜在非激素男性避孕药靶标：睾丸特异性溴结构域 BRDT。文献中描述了含有溴结构域的蛋白质的有效抑制剂，但尚未设计、制备和测试 BRDT 特异性化合物。BET 家族的溴结构域蛋白之间具有高度相似性，因此开发选择性和特异性抑制剂既困难又必要。小分子对 BRDT 的选择性抑制是寻找新的非激素男性避孕药的一个令人兴奋的新靶标。
