ORGN 472 |
Reactivation of mutant p53 with serine derived molecules
| Jaclyn A. Iera, Michael C. Myers, and Daniel H. Appella. Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 |
| The protein p53 is an important tumor suppressor that, in damaged cells causes cell cycle arrest or apoptosis. A mutated form of p53, which is inactive, is found in approximately 50% of human tumor cells. Reactivation of mutant p53 with small organic molecules is being investigated as a new method to combat cancer. We have undertaken a research program, which aims to identify, synthesize, and test drug-like small molecules that can reactivate mutant p53, restoring its tumor suppression functions. Our drug-like molecules are based on PRIMA-1, a mutant p53 reactivator. We have identified two serine derived small molecules, which are able to reactivate mutant p53 proteins with a higher potency than PRIMA-1. These molecules contain chemically similar reactivity profiles when compared to PRIMA-1, but within a simple and easily modifiable framework. Certain functionality within key sites that have been identified is critical for reactivation of mutant p53. 
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Total Synthesis, Process R&D, Combinatorial, Bioorganic, Physical Organic Chemistry
8:00 PM-10:00 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- Hall D, Poster
Sci-Mix
8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix
Division of Organic Chemistry
The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004
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