Rational Design of Rho Protein Inhibitors
Abstract
Rho GTPases are molecular switches that fluctuate between on and off states. When active, these proteins function to remodel the actin cytoskeleton by interacting with a number of downstream effector molecules. Recent studies have linked the activation of Rho GTPases with the acquisition of a metastatic phenotype in many types of cancers, including inflammatory breast cancer (IBC). This proposal incorporates a rational approach to target these signaling proteins using small molecule inhibitors that would interfere with their ability to become activated by Rhofamily guanine nucleotide exchange factors (RhoGEFs). The author's strategy incorporates both virtual, structure-based screening and a complementary high throughput drug screen to identify small molecule inhibitors that interfere with Rho GTPase activation and signal transduction. Any inhibitors identified through this research can serve as useful tools for studying Rho-mediated signal transduction cascades and may lead to the development of novel cancer therapeutics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA434614
Entities
People
- Rafael J. Rojas
Organizations
- University of North Carolina at Chapel Hill