1. Academic Validation
  2. A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway

A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway

  • Chem Biol. 2009 Jun 26;16(6):657-66. doi: 10.1016/j.chembiol.2009.04.012.
Nathalie Bouquier 1 Emmanuel Vignal Sophie Charrasse Mylene Weill Susanne Schmidt Jean-Paul Léonetti Anne Blangy Philippe Fort
Affiliations

Affiliation

  • 1 Centre de Recherche de Biochimie Macromoléculaire, Universités Montpellier I et II, CNRS, 34293 Montpellier, France.
Abstract

RhoGEFs (guanine nucleotide exchange factors of the Rho GTPase family) are upstream regulators of cell adhesion and migration pathways, thus representing attractive yet relatively unexplored targets for the development of anti-invasive drugs. We screened for chemical inhibitors of TrioN, the N-terminal GEF domain of the multidomain Trio protein, and identified ITX3 as a nontoxic inhibitor. In transfected mammalian cells, ITX3 blocked TrioN-mediated dorsal membrane ruffling and Rac1 activation while having no effect on GEF337-, Tiam1-, or Vav2-mediated RhoA or Rac1 activation. ITX3 specifically inhibited endogenous TrioN activity, as evidenced by its ability to inhibit neurite outgrowth in nerve growth factor (NGF)-stimulated PC12 cells or C2C12 differentiation into myotubes. This study introduces a selective cell active inhibitor of the Trio/RhoG/Rac1 pathway and validates RhoGEFs as druggable targets.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16663
    98.88%, TrioN Inhibitor