16Mar 2023
Ebselen oxide and derivatives are new allosteric HER2 inhibitors for HER2‐positive cancers

Ebselen oxide and derivatives are new allosteric HER2 inhibitors for HER2‐positive cancers

The article discusses the need for new therapeutic approaches for cancers that overexpress the Human epidermal growth factor receptor 2 (HER2) due to resistance mechanisms and toxicity associated with current therapies. The article highlights that HER2 is stabilized in a catalytically repressed state by a direct interaction with members of the ezrin/radixin/moesin (ERM) family. In HER2‐overexpressing tumors, the low expression of moesin contributes to aberrant activation of HER2. The article suggests that ebselen oxide, a compound identified through a screen designed to find moesin‐mimicking compounds, is an efficient allosteric inhibitor of HER2, which can selectively inhibit proliferation of HER2+ cancer cells and can show a significant benefit in combination with current anti-HER2 therapeutic agents. Finally, ebselen oxide significantly blocked HER2+ breast tumor progression in vivo. The article concludes that ebselen oxide is a newly identified allosteric inhibitor of HER2 that can be considered for therapeutic intervention on HER2+ cancers.

  • #oncology

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