Applying click chemistry to discover the direct targets of the active components of traditional Chinese medicines.

Determining the target of a traditional Chinese medicine (TCM) is key to the research and development of the TCM and the determination of how the natural product works in the body. However, conventional methods for target identification in TCMs present certain limitations, particularly in terms of their limited efficiency and tendency to produce false-positive results. In recent years, click chemistry has become a revolutionary tool for TCM target research, leveraging its advantages of high specificity, bioorthogonal compatibility, and modular design. This study presents a systematic review of click chemistry applications in TCM target identification over the past decade; previous reviews have not fully explored the application of click chemistry in TCM target identification. This work focuses specifically on TCM-derived active components and establishes a "component-reaction-target" matching framework tailored to the unique structural and pharmacological features of TCMs. Through critical analysis of current methodological limitations, this work establishes a new paradigm for investigating multitarget synergistic mechanisms in TCM.