A Potent and Selective Inhibitor of Cdc42 GTPase

Authors

Zurab Surviladze, University of New Mexico
Anna Waller, University of New Mexico
J. Jacob Strouse, University of New Mexico
Cristian G. Bologa, University of New Mexico
Oleg Ursu, University of New Mexico
Virginia M. Salas, University of New Mexico
Genevieve K. Phillips, University of New Mexico
John F. Parkinson, University of New Mexico
Elsa Romero, University of New Mexico
Angela Wandinger-Ness, University of New Mexico
Larry A. Sklar, University of New Mexico
Chad E. Schroeder, University of Kansas
Denise S. Simpson, Cedarville UniversityFollow
Julica Nöth, University of Kansas
Jenna Wang, University of Kansas
Jennifer E. Golden, University of Kansas
Jeffrey Aubé, University of Kansas

Document Type

Web Publication

Publication Date

2010

Abstract

Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). Given the highly complementary nature of the function of the Rho family GTPases, Cdc42 selective inhibitors such as those reported here should help untangle the roles of the proteins in this family.

Keywords

Cdc42, GTPase, Rho family

Comments

In Probe Reports from the NIH Molecular Libraries Program. Bethesda, MD: National Center for Biotechnology Information, 2010.

PubMed ID

21433396

Recommended Citation

2010: Surviladze, Z., Waller A., Strouse, J., Bologa, C., & Ursu, O., A Potent and Selective Inhibitor of Cdc42 GTPase, submitted to National Institutes of Health.