Chemical biology of traditional Chinese medicine: A new paradigm driving target discovery and mechanism elucidation

<x>Abstract</x> The modernization and internationalization of Traditional Chinese medicine (TCM) have long been constrained by the “black box” problem of its complex compositional system and unclear mechanisms of action. Target discovery, as a core step in revealing drug action principles, is key to promoting TCM’s transition from “empirical medicine” to “precision medicine”. In recent years, the rapid development of chemical biology technologies has provided powerful tools to address this challenge. This article focuses on the latest progress in applying chemical biology strategies, such as molecular probes, click chemistry, fluorescent labeling, and photo-crosslinking microarrays, in TCM target identification research. Combined with typical case studies like Sapanone A and Eupalinolide B, it elaborates on how these cutting-edge technologies can precisely identify the direct targets of active TCM components, thereby achieving comprehensive mechanism analysis from cells and animals to clinical samples. Furthermore, this article prospectively discusses novel “supramolecular drugs” formed by the self-assembly of TCM components at the nanoscale and their unique biological effects. It also preliminarily constructs a modern scientific interpretation framework for TCM theories like “property-flavor-channel tropism” and “processing theory”, centered around target distribution and regulation. Finally, this article proposes that “chemical biology of TCM,” as a key driver to discover original drug targets derived from TCM theory, is posited to offer a novel paradigm for innovative drug discovery and to contribute significantly to the modernization and scientific elucidation of TCM theory.