Structure-activity relationships of Wee1 inhibitors: A review

Eur J Med Chem. 2020 Oct 1:203:112524. doi: 10.1016/j.ejmech.2020.112524.

Xingkai Du ¹, Jian Li ², Xiaojiao Luo ¹, Rong Li ³, Feng Li ³, Yiwen Zhang ⁴, Jianyou Shi ⁵, Jun He ⁶

Affiliations

1 State Key Laboratory of Biotherapy & Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.
2 Department of Pharmacy, West China Hospital Sichuan University, Chengdu, 610041, China.
3 West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
4 State Key Laboratory of Biotherapy & Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China. Electronic address: [email protected].
5 Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, China. Electronic address: [email protected].
6 State Key Laboratory of Biotherapy & Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China. Electronic address: [email protected].

PMID: 32688199 DOI: 10.1016/j.ejmech.2020.112524

Abstract

Wee1 kinase plays an important role in regulating G2/M checkpoint and S phase, and the inhibition of it will lead to mitotic catastrophe in Cancer cells with p53 mutation or deletion. Therefore, the mechanism of Wee1 kinase in Cancer treatment and the development of its inhibitors have become a research hotspot. However, although a variety of Wee1 inhibitors with different scaffolds and considerable activity have been successfully identified, so far no one has systematically summarized the structure-activity relationships (SARs) of Wee1 inhibitors. Previous reviews mainly focused on its mechanism and clinical application. To facilitate the rational design and development of Wee1 inhibitors in the future, this paper systematically summarizes its structural types, SARs and binding modes according to the Wee1 inhibitors reported in scientific journals, and also summarizes the regulatory effect of Wee1 kinase on cell cycle and the progress of its inhibitors in clinical application.

Keywords

Cancer therapy; Cell cycle checkpoint; Structure-activity relationships; Wee1 inhibitors.

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