Conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO). As this pathway generates numerous metabolites that are involved in various pathological conditions, IDOs and TDO represent important targets for therapeutic intervention. This pathway has especially drawn attention due to its importance in tumor resistance. Over the last decade, a large number of IDO and TDO inhibitors have been developed, many of which have entered clinical trials. Here, detailed structural comparisons of these three enzymes (with emphasis on their active sites), their involvement in cellular signaling, and their role(s) in pathological conditions are discussed. Furthermore, the most important recent inhibitors described in papers and patents and involved in clinical trials are reviewed, with a focus on both selective and multiple inhibitors. A short overview of the biochemical and cellular assays used for inhibitory potency evaluation is also presented. This review summarizes recent advances on IDO and TDO as potential drug targets, and provides the key features and perspectives for further research and development of potent kynurenine pathway inhibitors.

色氨酸转化为N-甲酰基犬尿氨酸是色氨酸代谢途径（即犬尿氨酸途径）的第一步和限速步骤。这种转化由三种酶同工型催化：吲哚胺 2,3-双加氧酶 1 (IDO1)、吲哚胺 2,3-双加氧酶 2 (IDO2) 和色氨酸 2,3-双加氧酶 (TDO)。由于该途径产生许多涉及各种病理状况的代谢物，IDO 和 TDO 代表了治疗干预的重要目标。由于其在肿瘤抗性中的重要性，该途径特别受到关注。在过去的十年中，开发了大量的 IDO 和 TDO 抑制剂，其中许多已进入临床试验。在这里，这三种酶的详细结构比较（重点是它们的活性位点），它们参与细胞信号传导，并讨论了它们在病理状况中的作用。此外，还回顾了论文和专利中描述的以及涉及临床试验的最近最重要的抑制剂，重点关注选择性和多重抑制剂。还简要概述了用于抑制效力评估的生化和细胞测定。本综述总结了 IDO 和 TDO 作为潜在药物靶点的最新进展，并为进一步研究和开发有效的犬尿氨酸途径抑制剂提供了关键特征和前景。还简要概述了用于抑制效力评估的生化和细胞测定。本综述总结了 IDO 和 TDO 作为潜在药物靶点的最新进展，并为进一步研究和开发有效的犬尿氨酸途径抑制剂提供了关键特征和前景。还简要概述了用于抑制效力评估的生化和细胞测定。本综述总结了 IDO 和 TDO 作为潜在药物靶点的最新进展，并为进一步研究和开发有效的犬尿氨酸途径抑制剂提供了关键特征和前景。