“Research published in Science reveals a new target for non-hormonal male contraception. The protein, a kinase called STK33, has been linked to infertility in male mice and humans. Researchers from Baylor College of Medicine, in collaboration with scientists at Promega Corporation, used DNA-Encoded Libraries (DELs) to screen billions of compounds and identify potent inhibitors that bind STK33. Their results show that STK33 inhibition produces a reversible contraceptive effect in mice, making the protein a promising sperm-specific target for further male contraceptive development. In addition, the studies show that the novel contraceptive molecule (CDD-2807) is safe when delivered to the male mice and only affects the function and morphology of the sperm.

“This research addresses our clear societal need for more safe, affordable and reversible options for contraception,” says Matt Robers, Senior Research Scientist at Promega. “Moreover, it demonstrates exciting methods for accelerating kinase drug discovery efforts in many areas.”

Many kinase inhibitors have been developed to treat various forms of cancer. However, members of the protein kinase family play pivotal roles in many aspects of human biology. Of the 538 kinases in the human genome, 160, including STK33, are considered “dark kinases” due to a lack of existing research on their structure and function. This landmark Science paper demonstrates the importance of kinase research beyond oncology to uncover new therapeutic opportunities.

The researchers used Promega NanoBRET Target Engagement Assays to characterize compound binding in live cells. In particular, the authors used the newly launched NanoBRET Target Engagement K192 Kinase Selectivity System to study the selectivity of the CDD-2807 inhibitor compound against a panel of 192 full-length kinases.

Contributions from Promega researchers, including Robers and Jennifer Wilkinson, were integral to this publication by Martin M. Matzuk and his team at Baylor College of Medicine.”