Ye Zixiang, Yue Linxiu, Shi Jiachen, Shao Mingmei, Wu Tao
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
J Cancer. 2019 Jun 2;10(12):2771-2782. doi: 10.7150/jca.31727. eCollection 2019.
Kynurenine (Kyn) pathway is a significant metabolic pathway of tryptophan (Trp). The metabolites of the Kyn pathway are closely correlated with numerous diseases. Two main enzymes, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO or TDO2), regulate the first and rate-limiting step of the Kyn pathway. These enzymes are directly or indirectly involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. Presently, an increasing number of potential mechanisms have been revealed. In the present review, we depict the structure of IDO and TDO and explicate their functions in various diseases to facilitate a better understanding of them and to indicate new therapeutic plans to target them. Moreover, we summarize the inhibitors of IDO/TDO that are currently under development and their efficacy in the treatment of cancer and other diseases.
犬尿氨酸(Kyn)途径是色氨酸(Trp)的一条重要代谢途径。Kyn途径的代谢产物与多种疾病密切相关。两种主要的酶,吲哚胺-2,3-双加氧酶(IDO)和色氨酸-2,3-双加氧酶(TDO或TDO2),调节Kyn途径的第一步和限速步骤。这些酶直接或间接参与各种疾病,包括炎症性疾病、癌症、糖尿病和精神障碍。目前,越来越多的潜在机制已被揭示。在本综述中,我们描述了IDO和TDO的结构,并阐述了它们在各种疾病中的功能,以便更好地理解它们,并指出针对它们的新治疗方案。此外,我们总结了目前正在开发的IDO/TDO抑制剂及其在癌症和其他疾病治疗中的疗效。