Cyclin proteins are key components of the regulation of cell cycle progression. They bind to and activate cyclin-dependent kinase (CDK) enzymes to influence downstream gene expression. CDKs are well established as drug targets in cancer, with many CDK2/4 inhibitors already in clinical use (e.g., abemaciclib, ribociclib and palbociclib). Directly disrupting cyclin-CDK interactions has more recently been identified for therapeutic potential, particularly to overcome CDK inhibitor resistance [1-2].

1. Shapiro JA, Dupper NJ, Fraga-Walton B, Bockus AT, Leung SSF, Yang K, Bhatt C, DeMart MK, Baldomero MP, Hernandez L et al.. (2026) Orally Bioavailable Cyclin A/B RxL Inhibitors: Optimization of a Novel Class of Macrocyclic Peptides That Target E2F-High and G1-S-Checkpoint-Compromised Cancers. J Med Chem, 69 (5): 5441-5460. [PMID:41721763]

2. Singh S, Gleason CE, Fang M, Laimon YN, Khivansara V, Xie S, Durmaz YT, Sarkar A, Ngo K, Savla V et al.. (2025) Targeting G1-S-checkpoint-compromised cancers with cyclin A/B RxL inhibitors. Nature, 646 (8085): 734-745. [PMID:40836083]