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ZCL278 is a potent and selective inhibitor of Cdc42 GTPase. It directly binds to the of the Cdc42 guanine nucleotide exchange factor intersectin (ITSN) and inhibits its functions (K_d ~6-11 µM). In Swiss 3T3 fibroblast cultures, ZCL278 abolished microspike formation and disrupted GM130-docked Golgi structures, two of the most prominent Cdc42-mediated subcellular events. ZCL278 reduces the perinuclear accumulation of active Cdc42 in contrast to NSC23766, a selective Rac inhibitor. ZCL278 suppresses Cdc42-mediated neuronal branching and growth cone dynamics as well as actin-based motility and migration in a metastatic prostate cancer cell line (i.e., PC-3) without disrupting cell viability. ZCL278 could be a powerful chemical tool for research of Cdc42 subclass of Rho GTPases in human pathogenesis, such as those of cancer and neurological disorders. 

How to Use:

• In vitro:  ZCL278 was used at 50 µM final concentration in various in vitro assays.
• In vivo: not reported

Reference: 

1. 1. Friesland A, et al. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility. (2013) Proc Natl Acad Sci USA. 110(4):1261-6.