STK33 inhibitor for reversible male contraception

A small molecule inhibitor of STK33, a kinase for which a causal mutation was identified in a family of sterile men, could be devenloped into a reversible male contraceptive that decreases sperm counts and motility.

In an in vitro screen of multiple DNA-encoded libraries spanning 3.9 billion molecules, a pair of hits was identified as able to bind STK33 in the presence of a broad spectrum kinase inhibitor. The compounds were then optimized to be smaller and more metabolically stable, yielding a 447 Da small molecule that inhibited STK33 kinase activity with an IC50 of 9.2 nM, at least nine times lower than its IC50 for other kinases, and was capable of crossing the blood-testis barrier. ...