Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting enzyme that catalyzes the kynurenine (Kyn) pathway of tryptophan metabolism in the first step, and the kynurenine pathway plays a fundamental role in immunosuppression in the tumor microenvironment. Therefore, researchers are vigorously developing IDO1 inhibitors, hoping to apply them to cancer immunotherapy. Nowadays, there have been 11 kinds of IDO1 inhibitors entering clinical trials, among which many inhibitors have shown good tumor inhibitory effect in phase I/II clinical trials. But the phase III study of the most promising IDO1 inhibitor compound 29 (Epacadostat) failed in 2018, which may be caused by the compensation effect offered by tryptophan 2,3-dioxygenase (TDO), the mismatched drug combination strategies, or other reasons. Luckily, dual-target inhibitors show great potential and advantages in solving these problems. In recent years, many studies have linked IDO1 to popular targets and selected many IDO1 dual-target inhibitors through pharmacophore fusion strategy and library construction, which enhance the tumor inhibitory effect and reduce side effects. Currently, three kinds of IDO1/TDO dual-target inhibitors have entered clinical trials, and extensive studies have been developing on IDO1 dual-target inhibitors. In this review, we summarize the IDO1 dual-target inhibitors developed in recent years and focus on the structure optimization process, structure-activity relationship, and the efficacy of in vitro and in vivo experiments, shedding a light on the pivotal significance of IDO1 dual-target inhibitors in the treatment of cancer, providing inspiration for the development of new IDO1 dual-target inhibitors.

吲哚胺2, 3-双加氧酶1（IDO1）是一种限速酶，第一步催化色氨酸代谢的犬尿氨酸（Kyn）通路，犬尿氨酸通路在肿瘤微环境中的免疫抑制中起基础性作用。因此，研究人员正在大力研发IDO1抑制剂，希望将其应用于癌症免疫治疗。目前，已有11种IDO1抑制剂进入临床试验，其中不少抑制剂在I/II期临床试验中显示出良好的肿瘤抑制效果。但最有希望的IDO1抑制剂化合物的III期研究29（Epacadostat）2018年失败，可能是由于色氨酸2,3-双加氧酶（TDO）提供的补偿效应、药物组合策略不匹配或其他原因。幸运的是，双靶点抑制剂在解决这些问题方面显示出巨大的潜力和优势。近年来，许多研究将IDO1与热门靶点联系起来，通过药效团融合策略和文库构建，筛选出众多IDO1双靶点抑制剂，增强了肿瘤抑制作用，减少了副作用。目前，3种IDO1/TDO双靶点抑制剂已进入临床试验阶段，IDO1双靶点抑制剂的研究也在展开。在这篇综述中，我们总结了近年来开发的IDO1双靶点抑制剂，重点关注结构优化过程、构效关系、