TITLE:
TDO Target Inhibitor Research Progress Review
AUTHORS:
Yuxuan Han, Peng Wang, Zhaolin Guo, Anran Xiang, Shuang Cao, Yongshou Chen
KEYWORDS:
Tryptophan Metabolism, Tryptophan 2, 3-Dioxygenase (TDO), Tumor Immune Evasion, TDO Inhibitors, Tumor Immunotherapy
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.3,
March
25,
2025
ABSTRACT: Tryptophan metabolism plays a key role in tumor immunology. Tryptophan 2,3-dioxygenase (TDO), as a key rate-limiting enzyme in this metabolic pathway, catalyzes the conversion of tryptophan into metabolites such as kynurenine, which can modulate immune cell functions and promote tumor immune evasion. Therefore, it has become a potential target for tumor immunotherapy. This article comprehensively reviews the structure and biological functions of TDO, explores its mechanisms of action in the tumor microenvironment, and summarizes its expression patterns and prognostic correlations in different types of tumors. Additionally, this review covers the mechanisms of action and research progress of TDO inhibitors, including the structural optimization and activity studies of indole derivatives, naphthotriazole diones, aminoisoxazoles, tryptanthrins, platinum (IV) complexes, and small molecule conjugates. Although most TDO inhibitors are still in the laboratory research stage, they show broad application prospects in tumor immunotherapy. Future research directions should include optimizing existing inhibitor structures, exploring new design strategies, and strengthening clinical studies to develop highly effective and low-toxicity TDO inhibitors, providing new therapeutic options for cancer patients.