Probe-based target fishing technologies for identifying molecular targets of triptolide and celastrol from Tripterygium wilfordii : recent advances and perspectives

Bioactive constituents of Tripterygium wilfordii Hook. f. possess potent pharmacological activities but are constrained by a narrow therapeutic window and prominent toxicities. Triptolide and celastrol are representative constituents for which direct target identification is essential to clarify efficacy–toxicity mechanisms. Probe-based target fishing and chemical proteomics enable direct profiling of protein engagement in complex biological systems. This review summarizes the principles and applications of these technologies in identifying therapeutic and toxicity-related targets of triptolide and celastrol, critically evaluates current methodological limitations, and highlights future directions for target validation, toxicity reduction, efficacy optimization, and mechanism-based drug development.