Abstract
Wee1, a protein kinase, regulates the G 2 checkpoint in response to DNA damage. Preclinical studies have elucidated the role of wee1 in DNA damage repair and the stabilization of replication forks, supporting the validity of wee1 inhibition as a viable therapeutic target in cancer. MK-1775, a selective and potent small-molecule inhibitor of wee1, is under clinical development as a potentiator of DNA damage caused by cytotoxic chemotherapies. We present a review of the role of wee1 in the cell cycle and DNA replication and summarize the clinical development to date of this novel class of anticancer agents.
Keywords:
DNA damage; G2 checkpoint; MK 1775; cell cycle; cyclin-dependent kinase.
MeSH terms
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Antineoplastic Agents / therapeutic use
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Antineoplastic Agents / toxicity
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Clinical Trials as Topic
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DNA Damage / drug effects
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DNA Damage / radiation effects
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DNA Repair
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G2 Phase Cell Cycle Checkpoints / drug effects
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Humans
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Neoplasms / drug therapy
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Neoplasms / radiotherapy
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Neoplasms / therapy*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Pyrazoles / therapeutic use
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Pyrazoles / toxicity
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Pyrimidines / therapeutic use
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Pyrimidines / toxicity
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Pyrimidinones
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RNA Interference
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Nuclear Proteins
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Pyrazoles
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Pyrimidines
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Pyrimidinones
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Protein-Tyrosine Kinases
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WEE1 protein, human
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adavosertib