吲哚胺2,3-双加氧化酶1及其抑制剂的研究

 吲哚胺2,3-双加氧化酶1( indoleamine 2,3-dioxygenase 1,IDO1)是肝脏以外催化色氨酸沿着犬尿氨酸途径(kynurenine pathway,KP)分解代谢的限速酶。IDO1过度活化而引起KP的神经毒性产物喹啉酸(quinolinic acid,QUIN)的蓄积,是导致神经紊乱和神经退行性疾病的重要原因。IDO1同时又是免疫耐受酶,在诱导母胎免疫耐受和肿瘤免疫逃逸中均发挥重要作用,被视为新的免疫检查点。IDO1与阿尔茨海默病、老年性白内障、癌症等多种疾病发病机制的相关性已被证实,因此IDO1抑制剂作为极具潜能的药物受到日益广泛的关注。本文就IDO1的生物活性及其抑制剂的研究作一综述。

The study of indoleamine 2,3-dioxygenase 1 and its inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) is an extrahepatic enzyme that catalyzes the first and rate-limiting step in the catabolism of the essential amino acid tryptophan (Trp) along the kynurenine pathway (KP).The overexpression or overactivation of IDO1 leads to the accumulation of downstream neurotoxic metabolite,quinolinic acid (QUIN),which is the main reason of nervous disorder and neurodegenerative disease.As an immunotolerant enzyme,IDO1 is regarded as a new immune checkpoint due to vital role in both the induction of maternal-fetal immune tolerance and tumor immune escape.Furthermore,the correlation between IDO1 and the pathogenesis of Alzheimer′s disease (AD),age-related cataracts and cancer has been confirmed,which brings IDO1 inhibitors increasingly widespread attention as promising drugs.This paper reviews the biological activity and development of IDO1 inhibitors.