Inhibitors of cell cycle checkpoint target Wee1 kinase - a patent review (2003-2022)

DNA damage repair in most malignancies with mutation of p53 is more dependent on the G2/M checkpoint. Wee1 kinase is a key regulator of the G2/M checkpoint. If Wee1 is inhibited, it results in cells with unrepaired DNA damage entering mitosis prematurely, leading to mitotic catastrophe and subsequen...

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Bibliographic Details
Published in:Expert opinion on therapeutic patents Vol. 32; no. 12; pp. 1217 - 1244
Main Authors: Yan, Jingxue, Zhuang, Lili, Wang, Yong, Jiang, Yiqing, Tu, Zhenlin, Dong, Chao, Chen, Yadong, Zhu, Yong
Format: Journal Article
Language:English
Published: England Taylor & Francis 02.12.2022
Subjects:
anticancer
cell cycle checkpoint
Cell Cycle Checkpoints
Cell Cycle Proteins
Cell Line, Tumor
clinical development
Humans
inhibitors
Neoplasms - drug therapy
Neoplasms - genetics
Patents as Topic
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Wee1 kinase
clinical development
inhibitors
patent
Wee1 kinase
anticancer
cell cycle checkpoint
ISSN:1354-3776, 1744-7674, 1744-7674
Online Access:Get full text
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Summary:DNA damage repair in most malignancies with mutation of p53 is more dependent on the G2/M checkpoint. Wee1 kinase is a key regulator of the G2/M checkpoint. If Wee1 is inhibited, it results in cells with unrepaired DNA damage entering mitosis prematurely, leading to mitotic catastrophe and subsequent cell death via the apoptotic program. Therefore, inhibition of Wee1 kinase which overexpressed in several cancer cell lines has emerged as a promising therapy for cancer treatment. This review summarizes for the first time the structures of small-molecule inhibitors of Wee1 reported in patents published from 2003 to 2022 and the recent clinical developments. It also provides perspectives on the challenges and the future directions. We used different methods to search different databases (PubMed, Reaxys, clinicaltrials.gov)for the literature we needed. Although the small-molecule inhibitors of Wee1, Adavosertib, and ZN-C3 have entered the clinical phase II, the clinical toxicity exhibited by Adavosertib remains the subject of greater concern. The use of Wee1 inhibitors as monotherapy or in combination therapy remains the main trend in Wee1 inhibitors at present.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
ISSN:1354-3776
1744-7674
1744-7674
DOI:10.1080/13543776.2022.2166827