Researchers have succeeded in identifying an active substance that effectively inhibits sperm formation in mice. This could be an important step towards the first non-hormonal contraceptive for men, write researchers in the "Journal of Medicinal Chemistry".

The team took a closer look at a protein involved in cell division, cyclin-dependent kinase (CDK2). It plays a role in the production of sperm: Mice without a CDK2 receptor are infertile. The team discovered a previously unknown binding site of CDK2 and a dye molecule that binds exactly there. Starting from this dye, the researchers examined tens of thousands of different substances to find others that fit as perfectly as possible to the binding site. This is because CDK2 belongs to a family of enzymes. To avoid side effects, it is important that a drug candidate really only inhibits CDK2.

The researchers investigated the three most promising candidates and then optimised them further. The best of them, EF-4-177, was detectable in the body for a long time and entered the testes of mice. After 28 days, the sperm count of the animals had decreased by about 45 percent.

Previously, the team had discovered a receptor for vitamin A that is suitable as a contraceptive method and showed no side effects in animal experiments. Several options increase the likelihood that a candidate will make it into clinical trials in humans and eventually onto the market as the first non-hormonal contraceptive for men.

Quelle: DOI 10.1021/acs.jmedchem.2c01731