Promega Aids Study on Reversible, Non-Hormonal Male Contraception

A groundbreaking study published in Science unveils a novel target for non-hormonal male contraception, focusing on a protein kinase known as STK33. This kinase has been implicated in infertility among male mice and humans. The research team, comprising scientists from Baylor College of Medicine and Promega Corporation, utilized DNA-Encoded Libraries (DELs) to screen billions of potential small-molecule inhibitors, ultimately identifying potent compounds that bind to STK33.

The study's findings indicate that inhibiting STK33 results in a reversible contraceptive effect in male mice, suggesting that this protein could be a promising target for the development of male contraceptives. The novel contraceptive molecule identified, CDD-2807, was shown to be safe for use in male mice, affecting only the function and morphology of sperm without causing other adverse effects.

Matt Robers, a Senior Research Scientist at Promega, emphasized the societal need for more safe, affordable, and reversible contraceptive options. He also highlighted the innovative methods demonstrated in this research for accelerating kinase drug discovery efforts across various fields.

Kinase inhibitors have traditionally been developed to treat cancer, but this research underscores the broader biological significance of the protein kinase family, which includes 538 kinases in the human genome. Notably, 160 of these kinases, including STK33, are classified as "dark kinases" due to the limited research on their structure and function. This study underscores the importance of expanding kinase research beyond oncology to uncover new therapeutic opportunities.

To characterize compound binding in live cells, the researchers employed Promega NanoBRET Target Engagement Assays. Specifically, they used the newly launched NanoBRET Target Engagement K192 Kinase Selectivity System to study the selectivity of the CDD-2807 inhibitor against a panel of 192 full-length kinases. The contributions of Promega researchers, including Matt Robers and Jennifer Wilkinson, were crucial to the success of this publication by Martin M. Matzuk and his team at Baylor College of Medicine.

The findings from this study present a significant advancement in the field of male contraception. By identifying STK33 as a target and demonstrating the efficacy and safety of the CDD-2807 inhibitor, the research opens the door for further development and potential clinical applications of non-hormonal male contraceptives. Additionally, the study highlights the broader potential for kinase inhibitors beyond their traditional use in oncology, suggesting new avenues for therapeutic innovation.

Promega Corporation, a leader in life sciences solutions, played a pivotal role in this research. With a portfolio of over 4,000 products, Promega supports a wide range of scientific inquiries, including cell biology, genetic analysis, drug development, and diagnostics. The company's technologies have been instrumental in advancing research across academic, governmental, and industrial laboratories worldwide.

This landmark study not only advances the field of contraception but also exemplifies the importance of interdisciplinary collaboration and innovative techniques in uncovering novel therapeutic targets. As research continues, the potential for new and effective non-hormonal contraceptive options for men becomes increasingly promising.

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