ITX3 is a specific and nontoxic inhibitor of the TrioN (N-terminal GEF domain of the multidomain Trio protein) with IC50 of 76 uM; inhibits TrioN-stimulated RhoG exchange in vitro.IC50 value: 76 uM [1]Target: TrioN inhibitorIn 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 [1]. ITX3 repressed the Rac1 activity and dose dependently up-regulated the E-cadherin protein level in the Tara-KD cells [2].
[1]. Bouquier N, et al. A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway. Chem Biol. 2009 Jun 26;16(6):657-66. [2]. Yano T, et al. Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling. J Cell Biol. 2011 Apr 18;193(2):319-32.