Uses
ZCL 278, is a selective inhibitor of Cdc42, and effectively inhibits EGF-stimulated Cdc42 activity including microspike formation in 3T3 fibroblasts and neuronal branching in primary neonatal cortical neurons.
Biological Activity
zcl278 is a selective inhibitor of cdc42 with kd value of 11.4 μm [1].cell division control protein 42 homolog (cdc42) is a small gtpase that belongs to the rho family and plays an important role in regulating diverse cellular functions including cell morphology, endocytosis, migration, and cell cycle progression [2].zcl278 is a potent cdc42 inhibitor and has a different selectivity with the reported cdc42 inhibitor ml141. when tested with human metastatic prostate cancer pc-3 cells, zcl278 showed inhibitory function on rac/cdc42 phosphorylation and the function increasing as the more-treated time. in cortical neurons, zcl278 treatment suppressed neuronal branch number and inhibited growth cone motility at the dose of 50 μm for 5 or 10 min. treated serum-starved swiss 3t3 fibroblasts cdc42 activator following administration of zcl278 at the dose of 50 μm for 1 h exhibited a significant decrease (nearly 80%) in gtp-cdc42 and disrupted perinuclear distribution of active cdc42. [1]. when tested with rat cerebellar granule neurons (cgns), pre-treated with zcl278 before exposed to naaso2 increased cell viability in a dose-dependent manner (20, 50 and 100μm) [3].
References
[1]. friesland, a., et al., small molecule targeting cdc42-intersectin interaction disrupts golgi organization and suppresses cell motility. proc natl acad sci u s a, 2013. 110(4): p. 1261-6.
[2]. selamat, w., et al., the cdc42 effector kinase pak4 localizes to cell-cell junctions and contributes to establishing cell polarity. plos one, 2015. 10(6): p. e0129634.
[3]. liu, x., et al., neuroglobin plays a protective role in arsenite-induced cytotoxicity by inhibition of cdc42 and rac1gtpases in rat cerebellar granule neurons. cell physiol biochem, 2015. 36(4): p. 1613-1627.
