Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception

  • Future Med Chem. 2025 Mar;17(5):607-627. doi: 10.1080/17568919.2025.2463868.
Jeanine Giarolla  1  2 ,  Kelsey A Holdaway  1 ,  Maryam Nazari  1 ,  Laila Aiad  3 ,  Bidisha Sarkar  3 ,  Gunda I Georg  4
Affiliations
  • 1. Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
  • 2. Departamento de Farmacia, School of Pharmaceutical Sciences, University of São Paulo-USP, São Paulo, SP, Brazil.
  • 3. Department of Chemistry, University of Minnesota, Minneapolis, MN, USA.
  • 4. Medicinal Chemistry, University of Minnesota Twin Cities, Minneapolis, MN, USA.
PMID: 40034037 DOI: 10.1080/17568919.2025.2463868
Abstract

The review discusses progress in discovering cyclin-dependent kinase 2 (CDK2) inhibitors for Cancer treatment and their potential for male contraception. It summarizes first-, second-, and third-generation CDK inhibitors and selective CDK2 inhibitors currently in clinical trials for Cancer. Novel strategies to discover allosteric inhibitors, covalent inhibitors, and degraders are also discussed.

Keywords
CDK2 inhibitors; Oncological therapeutics; Spy1; clinical trials; covalent binders; degraders; male contraception; orthosteric and allosteric.
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