Labeled and Label-Free Target Identifications of Natural Products.

Target identification, employing chemical proteomics, constitutes a continuous challenging endeavor in the drug development of natural products (NPs). Understanding their targets is crucial for deciphering their mechanisms and developing potential probes or drugs. Identifications fall into two main categories: labeled and label-free techniques. Labeled methods use the molecules tagged with markers such as biotin or fluorescent labels to easily detect interactions with target proteins. Thorough structure-activity relationships are essential before labeling to avoid changes in the biological activity or binding specificity. In contrast, label-free technologies identify target proteins without modifying natural products, relying on changes in the stability, thermal properties, or precipitation in the presence or absence of these products. Each approach has its advantages and disadvantages, offering a comprehensive understanding of the mechanisms and therapeutic potential of the NPs. Here, we summarize target identification techniques for natural molecules, highlight case studies of notable NPs, and explore future applications and directions.