NSC23766

Selective inhibitor of Rac1-GEF interaction. Prevents Rac1 activation by Rac-specific guanine nucleotide exchange factors (GEFs) Trio and Tiam1 (IC50 ca. 50 μM) with no effect on the closely related Cdc42 or RhoA. In cells, it blocks serum or PDGF-induced Rac-1 activation and lamellipodia formation. NSC-23766 suppressed the growth of wild-type NIH 3T3 cells but was inactive in cells expressing the constitutively active Rac1 mutant, L61Rac1 [1]. It is a useful tool to probe the involvement of Rac1 in cell signalling [2]. Off target effect: antagonist at muscarinic acetylcholine receptors [3]. Cell permeable.

References:

1) Gao et al. (2004), Rational design and characterization of a RAc GTPase-specific small molecule inhibitor;  Proc. Natl. Acad. Sci. USA, 101 7618

2) Shankar et al. (2013), Raft endocytisus of AMF regulates  mitochondrial dynamics through Rac1 signaling and the Gp78 ubiquitin ligase;  J. Cell Sci., 126 3295

3) Levay et al. (2013), NSC23766, a widely used inhibitor of Rac1 activation, additionally acts as a competitive antagonist at muscarinic acetylcholine receptors;  J. Pharmacol. Exp. Ther., 347 69