Natural products, characterized by structural diversity and broad biological activities, have become a major source for drug discovery and lead compound identification. However, unclear targets have seriously hindered the research and development of many natural products, making target identification a critical bottleneck and a major focus in this field. In recent years, extensive efforts have been devoted to the discovery of natural product targets, and a relatively systematic methodological framework has gradually been established. According to whether chemical modification is required, current target identification strategies for natural products can be broadly classified into two categories:labeled and label-free approaches. This review systematically summarizes the major target identification techniques within these two strategic frameworks, with particular emphasis on their underlying principles, technical advantages, limitations, applicable scenarios, and representative applications, in order to provide references and insights for mechanistic studies and target discovery of natural products.

natural products  /  target discovery  /  activity probes  /  click chemistry  /  labeling-based strategies  /  label-free approaches