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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].

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