Despite huge progress in hormonal therapy and improved in vitro fertilization methods, the success rates in infertility treatment are still limited. A recently discovered mechanism revealed the interplay between the plasma protein fetuin‐B and the cortical granule‐based proteinase ovastacin to be a novel key mechanism in the regulation of fertilization. Upon sperm–egg fusion, cleavage of a distinct zona pellucida component by ovastacin destroys the sperm receptor, enhances zona robustness, and eventually provides a definitive block against polyspermy. An untimely onset of this zona hardening prior to fertilization would consequently result in infertility. Physiologically, this process is controlled by fetuin‐B, an endogenous ovastacin inhibitor. Here we aimed to discover small‐molecule inhibitors of ovastacin that could mimic the effect of fetuin‐B. These compounds could be useful lead structures for the development of specific ovastacin inhibitors that can be used in infertility treatment or in vitro fertilization

中文翻译：

---

Astacin金属蛋白酶Ovastacin的潜在小分子抑制剂的初步评估，该药物是治疗女性不育症的新型药物。

尽管荷尔蒙疗法取得了巨大进步并在体外得到了改善受精方法的不育治疗成功率仍然有限。最近发现的一种机制揭示了血浆蛋白fetuin-B与皮质颗粒蛋白酶ovastacin之间的相互作用是调节受精的新关键机制。精卵融合后，卵清蛋白对独特的透明带成分的切割会破坏精子受体，增强透明带的牢固性，并最终阻止多精子。因此，在受精之前这种透明性硬化的不适当地发作会导致不孕。从生理上讲，此过程由内源性卵磷脂抑制因子fetuin-B控制。在这里，我们旨在发现可以模仿胎球蛋白B效果的小分子卵泡抑素抑制剂。体外授精