Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration
Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration
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DOI：
10.1093/biolre/ioaa052
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发表时间：
2020-08-01
影响因子：
3.6
通讯作者：
Buck, Jochen
中科院分区：
文献类型：
--
作者：
Balbach, Melanie;Fushimi, Makoto;Buck, Jochen
开发新的男性或女性非激素口服避孕药的努力假设有效和安全，目标必须是（1）生育力所必需的;（2）适合小分子抑制剂的靶向;（3）仅限于生殖系。从这个角度来看，我们质疑第三个假设，并提出尽管可溶性腺苷酸环化酶（sAC：ADCY 10）广泛表达，但它对男性生育能力至关重要，是一个有效的靶点。我们假设，急性作用的sAC抑制剂可以为男性提供口服、按需、非激素避孕，而不会产生基于机制的不良影响。为了测试这一概念，我们描述了学术界和公私药物发现研究所的独特能力之间的合作。
Efforts to develop new male or female nonhormonal, orally available contraceptives assume that to be effective and safe, targets must be (1) essential for fertility; (2) amenable to targeting by small-molecule inhibitors; and (3) restricted to the germline. In this perspective, we question the third assumption and propose that despite its wide expression, soluble adenylyl cyclase (sAC: ADCY10), which is essential for male fertility, is a valid target. We hypothesize that an acut-eacting sAC inhibitor may provide orally available, on-demand, nonhormonal contraception for men without adverse, mechanism-based effects. To test this concept, we describe a collaboration between academia and the unique capabilities of a public-private drug discovery institute.