Male contraceptive development: A medicinal chemistry perspective.

There is a need for non-hormonal contraceptives. One area that needs further investigation is the development of male contraceptives. Comparatively little is understood about potential drug targets in men to achieve a reversible contraceptive effect.

A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity.

There is an urgent need to develop new methods for male contraception, however a major barrier to drug discovery has been the lack of validated targets and the absence of an effective high-throughput phenotypic screening system. To address this deficit, we developed a fully-automated robotic screening platform that provided quantitative evaluation of compound activity against two key attributes of human sperm function: motility and acrosome reaction. In order to accelerate contraceptive development, we screened the comprehensive collection of 12,000 molecules that make up the ReFRAME repurposing library, comprising nearly all the small molecules that have been approved or have undergone clinical development, or have significant preclinical profiling.

Sperm are promiscuous and CatSper is to blame….

EMBO J 31 7, 1654–1665 February 21 2012 A sperm-specific cation channel (CatSper) facilitates the entry of calcium necessary for rapid changes in sperm motility allowing the cell to navigate the hurdles of the female reproductive tract and successfully to locate the egg. Brenker and colleagues show that CatSper is (directly) activated by a diverse range of small organic molecules that are reported to evoke chemotaxis in human spermatozoa, suggesting that CatSper may function as a polymodal, chemosensory calcium channel. Additionally, they provide strong evidence that calcium entry into the spermatozoon does not employ specific, G protein-coupled odorant receptors or activation of trans-membrane adenylate cyclase and is not induced by cyclic nucleotides.