Structure-based design of anticancer drugs based on β-elemene: Research foundations and development potential

β-elemene, a bioactive compound derived from traditional Chinese medicine (TCM), has been clinically used in cancer therapy. However, its molecular physicochemical properties require further optimization, and its precise anticancer mechanisms remain unknown. In modern drug development, structure-based drug design (SBDD) has significantly conserved resources, with computer-aided techniques such as molecular docking and molecule generation playing essential roles. A comprehensive review of existing molecular biology studies and virtual docking experiments led to the hypothesis that methyltransferase-like 3 (METTL3) may serve as a potential target of β-elemene. This discovery establishes a scientific foundation for integrating advanced, rational drug design strategies with β-elemene to enhance the therapeutic efficacy of TCM. Moreover, current (AI)-based molecular generation models were examined, focusing on de novo molecular generation and lead optimization models. Their applications in the rational drug design of β-elemene were preliminarily explored to identify potential strategies for developing more potent anticancer derivatives by analyzing ligand-receptor interactions.