Wiskostatin

Wiskostatin is a potent and selective inhibitor of neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin polymerization by stabilization of the closed, autoinhibited conformation, thereby preventing Arp2/3 complex activation. Wiskostatin is also a dynamin inhibitor with an IC50 value of 20.7 μM and a potent inhibitor of clathrin-mediated endocytosis with an IC50 value of 6.9 μM. Wiskostatin causes a rapid, profound, and irreversible decrease in cellular ATP levels. Wiskostatin also induces disassembly of podosomes in a murine monocyte cell line[1][2][3][4][5].

[1]Guerriero CJ, et al. N-WASP inhibitor wiskostatin nonselectively perturbs membrane transport by decreasing cellular ATP levels. Am J Physiol Cell Physiol. 2007;292(4):C1562-C1566. |[2]Cossar PJ, et al. Wiskostatin and other carbazole scaffolds as off target inhibitors of dynamin I GTPase activity and endocytosis. Eur J Med Chem. 2023 Feb 5;247:115001. |[3]Nürnberg A, et al. Pharmacological inhibition of actin assembly to target tumor cell motility. Rev Physiol Biochem Pharmacol. 2014;166:23-42. |[4]Dovas A, et al. Regulation of podosome dynamics by WASp phosphorylation: implication in matrix degradation and chemotaxis in macrophages. J Cell Sci. 2009 Nov 1;122(Pt 21):3873-82. |[5]Park H, et al. Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP. Mol Biol Cell. 2009 Nov;20(21):4500-8.