吲哚胺2,3-双加氧酶抑制剂临床研究现状

Clinical research status of indoleamine 2,3-dioxygenase inhibitors

吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)不仅是启动色氨酸分解代谢的关键酶,也是一种与机体外周免疫耐受现象和机体免疫抑制作用相关的免疫调节酶。IDO作为一种免疫抑制分子,在多种恶性肿瘤组织中高表达,并与不良预后密切相关,因此有效抑制IDO活性可启动体内抗肿瘤免疫反应。将IDO抑制剂与手术、化疗、放疗等进行联合治疗,是近年来不断被探究且前景良好的肿瘤治疗方向。IDO抑制剂种类主要包括:1-甲基-DL-色氨酸(1-methyl-DL-tryptophan,1-MT)和epacadostat为代表的竞争性抑制剂,navoximod为代表的非竞争性抑制剂,以及BMS-986205、exiguamine A等其他种类的抑制剂。IDO抑制剂种类繁多,但进入临床试验阶段的较少,本文主要针对indoximod、epacadostat、navoximod、BMS-986205和HTI-1090等IDO抑制剂的临床研究现状进行阐述。

Indoleamine 2,3-dioxygenase(IDO)is not only a key enzyme that can initiate the catabolic process of tryptophan,but also an immunomodulatory enzyme associated with peripheral immune tolerance and immune suppression.As an important immunosuppressive molecule,IDO is highly expressed in multiple malignant tumors,and it is also closely associated with poor prognosis.Therefore,effective inhibition of the IDO activity can initiate an anti-tumor immune response.IDO inhibitors,in combination with surgical treatment,chemotherapy,radiotherapy and other basic treatment methods,are worthy of exploration and has a promising prospect in cancer treatment.IDO inhibitors mainly consist of the competitive inhibitors such as 1-methyl-DLtryptophan and epacadostat which belongs to the tryptophan analogs;the non-competitive IDO inhibitor such as the navoximod;and other types of inhibitors such as BMS-986205,exiguamine A and so on.Even though there are different kinds of IDO inhibitors,few of them have entered into clinical trials.Thus,in the present review,we focus on the IDO inhibitors such as indoximod,epacadostat,navoximod,BMS-986205 and HTI-1090.Furthermore,the status of their clinical development and status also have been described.