Identification of a rhodium(iii) complex as a Wee1 inhibitor against TP53-mutated triple-negative breast cancer cells

Chem Commun (Camb). 2018 Mar 6;54(20):2463-2466. doi: 10.1039/c7cc09384e.

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

  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Mutation
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Rhodium / chemistry
  • Rhodium / pharmacology*
  • Structure-Activity Relationship
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Cell Cycle Proteins
  • Coordination Complexes
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Rhodium
  • Protein-Tyrosine Kinases
  • WEE1 protein, human