ZCL278 is a modulator of Cdc42 through directly binding to Cdc42 with Kd of 11.4 μM.
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ZCL278 is a potent, cell-permeable inhibitor specific to Cdc42, suppressing actin-based cellular functions such as Golgi organization and cell motility. In Swiss 3T3 fibroblast cultures, ZCL278 disrupts microspike formation and GM130-docked Golgi structures, prominent Cdc42-mediated subcellular events. It reduces perinuclear accumulation of active Cdc42 compared to NSC23766, a selective Rac inhibitor. ZCL278 also inhibits Cdc42-mediated neuronal branching, growth cone dynamics, actin-based motility, and migration in PC-3 metastatic prostate cancer cells without impacting cell viability [1]. ZCL278 acts as an entry inhibitor for Junin virus (JUNV), vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus, but not for nonenveloped poliovirus. It efficiently inhibits chemically induced filopodium formation, a process dependent on Cdc42 activity. Dose-response experiments in Vero cells show that ZCL278, up to 200 μM, is not toxic but inhibits JUNV with an IC50 of ~14 μM, measured by flow cytometry [2].
体内研究
ZCL278 decreases JUNV RNA load in the spleen over 33-fold, with JUNV RNA undetectable in 5 out of 8 mice, similar to Gabapentin-treated mice, indicating ZCL278's ability to halt JUNV replication [2].
体外研究
ZCL278 is a potent, cell-permeable inhibitor specific to Cdc42, suppressing actin-based cellular functions such as Golgi organization and cell motility. In Swiss 3T3 fibroblast cultures, ZCL278 disrupts microspike formation and GM130-docked Golgi structures, prominent Cdc42-mediated subcellular events. It reduces perinuclear accumulation of active Cdc42 compared to NSC23766, a selective Rac inhibitor. ZCL278 also inhibits Cdc42-mediated neuronal branching, growth cone dynamics, actin-based motility, and migration in PC-3 metastatic prostate cancer cells without impacting cell viability [1].
ZCL278 acts as an entry inhibitor for Junin virus (JUNV), vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus, but not for nonenveloped poliovirus. It efficiently inhibits chemically induced filopodium formation, a process dependent on Cdc42 activity. Dose-response experiments in Vero cells show that ZCL278, up to 200 μM, is not toxic but inhibits JUNV with an IC50 of ~14 μM, measured by flow cytometry [2].
作用机制
ZCL278 is a small molecule that binds to Cdc42 residues to target the interaction between Cdc42 and intersectin and inhibits Cdc42-mediated cellular processes.
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