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A Primary Evaluation of Potential Small‐Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, a Novel Drug Target in Female Infertility Treatment
Author(s) -
Körschgen Hagen,
Jäger Christian,
Tan Kathrin,
Buchholz Mirko,
Stöcker Walter,
Ramsbeck Daniel
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000397
Subject(s) - polyspermy , zona pellucida , infertility , human fertilization , in vitro fertilisation , sperm , cortical granule , pharmacology , biology , microbiology and biotechnology , medicine , andrology , oocyte , anatomy , genetics , pregnancy , embryo
Abstract 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