Primary Evaluation of Potential Small Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, A Novel Drug Target in Female Infertility Treatment

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 as 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 at the discovery of small molecular inhibitors of ovastacin that could mimic the effect of fetuin-B. Hence, these compounds could be useful lead structures for the development of specific ovastacin inhibitors that can be utilized in infertility treatment or in vitro fertilization.