A Rac-specific competitive inhibitor of guanine nucleotide binding reduces metastasis in triple-negative breast cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40633540.
- Also identified by DOI 10.1016/j.xcrm.2025.102233 and PMC identifier 12281424.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The dysregulation of RAC1 activity is associated with neoplastic transformation, metastasis, and poor prognosis in several cancers. Here, we discover in silico a series of RAC1 inhibitors. The most potent of them, A41, specifically inhibits RAC1 with an original mechanism of action. We characterize A41 as a reversible inhibitor that competes with guanine nucleotide binding specifically on RAC proteins. A41 efficiently blocks RAC1 activity and RAC1-dependent cell functions including cell adhesion and migration. Chronic administration of A41 exhibits anti-metastatic effects in mouse models of triple-negative breast cancer, leading to an increase in the survival rate. Our findings suggest that this molecule, A41, could be a promising and powerful therapeutic agent for limiting invasive cancers in patients.
Medical subject headings
- Triple Negative Breast Neoplasms
- rac1 GTP-Binding Protein
- Guanine Nucleotides