Terpenoid-PROTAC Synergistic Strategy: A New Paradigm in Natural Product Drug Development

The integration of terpenoid natural products with proteolysis-targeting chimera(PROTAC) technology presents an innovative paradigm for addressing the challenge of “undruggable” proteins. In target discovery, PROTAC-mediated target protein degradation amplification combined with quantitative proteomics technology overcomes sensitivity limitations in multi-target analysis; in drug development, the rigid polycyclic scaffolds of terpenoids stabilize ternary complexes(target-ubiquitin ligase-PROTAC), while their chemical diversity facilitates tissue-selective optimization. A novel tripartite framework integrating degradomics, computational modeling, and synthetic biology is established to address critical challenges in linker design and off-target control. This strategy not only unlocks the therapeutic potential of natural products but also pioneers an interdisciplinary methodology for precision drug design, offering new possibilities for complex disease intervention.