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 acute-acting 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.

中文翻译：

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将先导化合物优化为按需非激素避孕药：利用公私药物发现研究所的合作†。

开发新的男性或女性非激素口服避孕药的努力假设要有效和安全，目标必须是 (1) 对生育必不可少的；(2) 适合小分子抑制剂靶向；(3) 仅限于种系。从这个角度来看，我们质疑第三个假设并提出尽管其广泛表达，但对男性生育能力至关重要的可溶性腺苷酸环化酶（sAC：ADCY10）是一个有效的目标。我们假设一种急性作用的 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。为了检验这一概念，我们描述了学术界与公私药物发现机构的独特能力之间的合作。