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

ABSTRACT: Human epidermal growth factor receptor 2 (ErbB2/HER2) is a tyrosine kinase receptor that is overexpressed in 25% of primary human breast cancers, as well as in multiple other cancers. HER2-targeted therapies improved progression-free and overall survival in patients with HER2⁺ breast cancers. However, associated resistance mechanisms and toxicity highlight the need for new therapeutic approaches for these cancers. We recently established that, in normal cells, HER2 is stabilized in a catalytically repressed state by direct interaction with members of the ezrin/radixin/moesin (ERM) family. In HER2-overexpressing tumors, the low expression of moesin contributes to the aberrant activation of HER2. Through a screen designed to find moesin-mimicking compounds, we identified ebselen o

SUBMITTER: Blasquez L 

PROVIDER: S-EPMC10552892 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature