CDK2 inhibitors for cancer therapy and male contraception
CDK2 inhibitors for cancer therapy and non-hormonal male contraception with high selectivity and reduced side effects.
Applications
- Cancer therapy
- Male contraception
- Research tool
Key Benefits & Differentiators
- Increased Selectivity: Allosteric inhibitors target a unique site, reducing off-target effects compared to traditional ATP-site inhibitors.
- Dual Application: Potential for use in both cancer chemotherapy and non-hormonal male contraception.
- Reduced Side Effects:Higher selectivity translates to fewer side effects, enhancing patient safety and treatment efficacy.
Technology Overview
Cyclin-dependent kinase 2 (CDK2) plays a crucial role in cell cycle regulation and is implicated in cancer progression and male fertility. While ATP-site binding inhibitors of CDK2 are known, they often lack selectivity, leading to side effects. The need for more selective inhibitors has driven the search for novel binding sites and mechanisms of inhibition.
Researchers at the University of Minnesota have developed new allosteric CDK2 inhibitors that bind outside the ATP site, leading to significant structural changes that prevent CDK2's association with its cyclin partners. These inhibitors have been optimized through structure-activity relationship (SAR) studies, resulting in highly potent nanomolar inhibitors. This breakthrough offers a targeted approach for cancer chemotherapy and a novel non-hormonal method for male contraception.
Phase of Development
TRL: 3-4The researchers are currently optimizing these inhibitors for further in vivo testing.
Desired Partnerships
This technology is now available for:- License
- Sponsored research
- Co-development
Please contact our office to share your business’ needs and learn more.
Researchers
- Gunda I. Georg, PhD Regents Professor, Department of Medicinal Chemistry
-
swap_vertical_circlelibrary_booksReferences (3)
- Erik B. Faber, Luxin Sun, Jian Tang, Emily Roberts, Sornakala Ganeshkumar, Nan Wang, Damien Rasmussen, Abir Majumdar, Laura E. Hirsch, Kristen John, An Yang, Hira Khalid, Jon E. Hawkinson, Nicholas M. Levinson, Vargheese Chennathukuzhi, Daniel A. Harki, Ernst Schönbrunn & Gunda I. Georg (2023), Development of Allosteric and Selective CDK2 Inhibitors for Contraception with Negative Cooperativity to Cyclin Binding, Nature Communications, 14, 3213
- Erik B. Faber, Nan Wang, Kristen John, Luxin Sun, Henry L. Wong, David Burban, Rawle Francis, Defeng Tian, Kwon H. Hong, An Yang, Liming Wang, Mazen Elsaid, Hira Khalid, Nicholas M. Levinson, Ernst Schönbrunn, Jon E. Hawkinson, and Gunda I. Georg (2023), Screening Through Lead Optimization of High Affinity, Allosteric Cyclin-dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives that Reduce Sperm Counts in Mice, Journal of Medicinal Chemistry, 66, 1928-1940
- Erik B Faber, Nan Wang, Gunda I Georg (2020), Review of Rationale and Progress Towards Targeting Cyclin-Dependent Kinase 2 (CDK2) for Male Contraception, Biology of Reproduction, 103, 357-367
-
swap_vertical_circlecloud_downloadSupporting documents (0)