Discovery of SIRT3 Inhibitors Using SAMDI Mass Spectrometry

This article describes the use of self-assembled monolayer desorption/ionization mass spectrometry, or SAMDI-MS—a label-free drug discovery tool—to characterize SIRT3 activity and discover inhibitors. SAMDI-MS was used to analyze a peptide array having 361 distinct acetylated peptides to identify an active SIRT3 substrate (GYKAcRGC). This peptide was used in a screen of 100,000 small molecules to identify inhibitors of SIRT3. A total of 306 SIRT3 inhibitors were identified, with one compound, SDX-437, having an IC50 of 700 nM with >100-fold selectivity for SIRT3 over SIRT1.
Source: Journal of Biomolecular Screening - Category: Molecular Biology Authors: Tags: Original Research Source Type: research