Specific Drug Target Identification with Quantitative Chemical Proteomics

摘要

As most drugs exert pharmacological effects by interacting with their target proteins, identification of which is a critical step in unravelling the mechanisms of drug action. It is also imperative for our understanding of the pharmacodynamics of a known drug, suggesting the potentially unrevealed actions and thus refining its future clinical applications. However, current in vitro affinity chromatography-based and in vivo activity-based protein profiling (ABPP) approaches generally face difficulties discriminating specific drug targets from non-specific ones. Therefore, there is an urgent need to develop comprehensive unbiased methods for specific target identification. Herein, we report a novel approach combining isobaric tag for relative and absolute quantitation (iTRAQ) with Clickable ABPP, named ICABPP, to specifically and comprehensively identify drug targets in situ (Fig. 1).