Jerrett Holdaway; Gunda I. Georg
Science, 2024, 384(6698), 849-850
https://doi.org/10.1126/science.adp6432

Abstract

Despite the current availability of contraceptive methods, nearly half of all pregnancies worldwide are unintended (1), resulting in over 70 million abortions annually and imposing considerable emotional, physical, and financial burdens on individuals and health care systems. Hormonal-based approaches for male contraception are being investigated in clinical trials, but none have been approved (2). Nonhormonal targets present a promising avenue with potentially fewer side effects, but few are pursued for drug discovery. On page 885 of this issue, Ku et al. (3) report a drug screen of multibillion compounds encoded with DNA that enabled the discovery and development of a potent inhibitor of serine/threonine-protein kinase 33 (STK33). This testis-enriched kinase is indispensable for male fertility in humans and mice. The STK33 inhibitor CDD-2807 induced reversible male infertility without measurable toxicity in mice. These findings provide substantial support that targeted nonhormonal approaches can be effective in the development of a male contraceptive pill.