Rac Inhibitor III

A cell-permeable carbazolylpyrimidine compound that inhibits Rac GEF interaction (by 45% of Vav2 interaction at 4 µM and by 35% of Tiam1 DH/PH domain interaction at 50 µM) by directly targeting Rac GEF binding domain and effectively reduces cellular Rac1-GTP (IC50 = 1.1 and 3 µM, respectively, in MDA-MB-435 and MDA-MB-231 cells) and Rac3-GTP (IC50 <1 µM in MDA-MB-435 cells) as well as PAK Thr423 phosphorylation (by 55% and 84%, respectively, at 2 and 4 µM in MDA-MB-435 cells), suppressing MDA-MB-435 Cdc42-GTP level only at higher concentrations (by 5%, 18% and 75%, respectively, at 4, 5, and 10 µM) and enhancing, instead of downregulating, RhoA-GTP level, presumably due to a cellular compensatory mechanism in response to Rac inhibition. NSC23766 (Cat. No. 553502), in comparison, is much less potent in reducing Rac1-GTP level in MDA-MB-435 (IC50 = 95 µM), but 10-times more effective in disrupting Rac1 and Tiam-1 DH/PH domain interaction.

EHop-016 is a potent and specific inhibitor of Rac1 and Rac3 GTPase activity that inhibits Vav2 interaction with Rac, Rac-activated PAK1, lamellipodia formation, and cell migration. EHop-016 inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation.

EHop-016 is a potent and specific inhibitor of Rac1 and Rac3 GTPase activity.