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Target intelligence / Profile preview
WEE1 G2 checkpoint kinase (WEE1)
- Target
- WEE1
- Molecular classification
- Enzyme, Protein kinase, Tyrosine kinase, Serine/threonine kinase (evolutionary origin)
01
Overview
WEE1 is a nuclear protein kinase that plays a critical role in cell cycle regulation, particularly at the G2/M and S-phase checkpoints. It inhibits Cdk1 by phosphorylating Tyr15 and Thr14, preventing premature entry into mitosis. WEE1 is also involved in DNA damage repair and replication fork stabilization. Overexpression of WEE1 is observed in various cancers, making it a therapeutic target. Inhibition of WEE1 can lead to mitotic catastrophe, particularly in cells with DNA damage. WEE1 inhibitors are being developed as chemosensitizers to enhance the efficacy of DNA-damaging agents.
- Other names
- WEE1 homolog (S. pombe)WEE1 G2 checkpoint kinase (human)WEE1 kinase
02
Mechanism of action
Inhibition of WEE1 leads to premature mitotic entry, especially in cells with DNA damage, resulting in mitotic catastrophe and cell death. Chemosensitization by abrogating the G2 checkpoint.
03
Biological functions
Cell cycle regulationG2/M checkpoint controlDNA damage responseDNA repairRegulation of Cdk1 activityCell size checkpointReplication fork stabilizationHistone modification
04
Disease associations
Cancer
05
Safety considerations
Mitotic catastrophePotential for off-target effectsChemosensitization may increase toxicity of DNA-damaging agents
06
Interacting drugs
MK-1775
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