STRATEGIES FOR DESIGNING DRUGS THAT TARGET THE SIR2 FAMILY OF ENZYMES

摘要

The instant invention describes methods of identifying compounds that modulate the activity of Sir2 enzymes. Sir2 enzymes form a unique class Of NAD+ dependent deacetylases required for diverse biological processes including transcriptional silencing, regulation of apoptosis, fat mobilization, and lifespan regulation. Sir2 activity is regulated by nicotinamide, a non-competitive inhibitor that promotes a base exchange reaction at the expense of deacetylation.