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

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.
Authors	Hagen Körschgen, Christian Jäger, Kathrin Tan, Mirko Buchholz, Walter Stöcker, Daniel Ramsbeck
Journal	ChemMedChem (ChemMedChem) Vol. 15 Issue 16 Pg. 1499-1504 (08 19 2020) ISSN: 1860-7187 [Electronic] Germany
PMID	32946206 (Publication Type: Journal Article)
Copyright	© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Chemical References	Amines Hydroxamic Acids Small Molecule Libraries Astl protein, mouse Metalloproteases
Topics	Amines (chemistry, pharmacology) Animals Biocatalysis Dose-Response Relationship, Drug Female Hydroxamic Acids (chemistry, pharmacology) Infertility, Female (drug therapy, metabolism) Metalloproteases (antagonists & inhibitors, metabolism) Mice Models, Molecular Molecular Structure Small Molecule Libraries (chemistry, pharmacology) Structure-Activity Relationship

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!