Research Progress of Wee1 Kinase and Its Inhibitors

Mitosis is completed under the precise control of cell cycle, which relies on the checkpoints of G₁/S phase, S phase and G₂/M phase to block the division process in time to ensure the integrity of genetic information. Since most human tumor cells have p53 mutations and p53 functional defects, the G₁/S phase checkpoints are inactivated, leading to higher dependence on the regulation of G₂/M checkpoints. The cell cycle regulatory protein Wee1 kinase is a key regulator of the G₂/M checkpoint. It achieves G₂/M phase blocked by phosphorylation of CDK1 Tyr15, which provides time for DNA repair. Inhibition of Wee1 can eliminate cell cycle block, make tumor cells enter mitosis prematurely, and produce replication stress and mitotic disaster. Wee1 is highly expressed in many tumors, so it is an ideal target for the treatment of tumors, with its inhibitors becoming a hot research topic. This article mainly introduces the mechanism of Wee1 kinase, its relevance to diseases, and the clinical application of small molecule inhibitors under investigation, in order to provide ideas for its further research and application.