Rational Design of Rho Protein Inhibitors
Annual summary, 18 Aug 2003-17 Aug 2004
NORTH CAROLINA UNIV AT CHAPEL HILL
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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 authors 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.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research