Abstract
The rhodium(iii) complex 1 was identified as a potent Wee1 inhibitor in vitro and in cellulo. It decreased Wee1 activity and unscheduled mitotic entry, and induced cell damage and death in TP53-mutated triple-negative breast cancer cells. 1 represents a promising scaffold for further development of more potent metal-based Wee1 antagonists.
MeSH terms
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / metabolism
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Cell Line
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology*
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Molecular Structure
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Mutation
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / metabolism
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / metabolism
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Rhodium / chemistry
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Rhodium / pharmacology*
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Structure-Activity Relationship
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Triple Negative Breast Neoplasms / drug therapy*
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Triple Negative Breast Neoplasms / genetics*
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Triple Negative Breast Neoplasms / metabolism
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Triple Negative Breast Neoplasms / pathology
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Tumor Suppressor Protein p53 / genetics*
Substances
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Cell Cycle Proteins
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Coordination Complexes
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Nuclear Proteins
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Protein Kinase Inhibitors
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TP53 protein, human
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Tumor Suppressor Protein p53
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Rhodium
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Protein-Tyrosine Kinases
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WEE1 protein, human