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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Benzomalvin E, an indoleamine 2,3-dioxygenase inhibitor isolated from Penicillium sp. FN070315
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Benzomalvin E, an indoleamine 2,3-dioxygenase inhibitor isolated from Penicillium sp. FN070315

机译：Benzomalvin E，一种从青霉属sp。分离出来的吲哚胺2,3-二加氧酶抑制剂。 FN070315

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摘要

Indoleamine 2,3-dioxygenase (IDO) is an extrahepatic heme-contain-ing dioxygenase that catalyzes the addition of oxygen across the C-2/ C-3 bond of indole ring of tryptophan (Trp). This is the initial and rate-limiting step in the catabolism of the essential amino acid Trp to N-formylkynurenine along the kynurenine pathway, the de novo biosynthetic route leading to NAD. T-cell lymphocytes are extremely sensitive to Trp shortage, which cause them to undergo cell cycle arrest in G1, and leads to apoptosis and immunosuppression. Degradation of Trp by the placenta inhibits T-cell proliferation and, as a result, prevents immunological rejection of tumor or fetus. IDO is expressed ubiquitously but predominately in cells within the immune system, where it is specifically induced in dendritic cells and macrophages at the site of inflammation by cytokines. It is known that IDO is overexpressed in a variety of diseases, including cancer, alzheimer's disease, age-related cataract and HIV encephalitis. Recent studies have shown that IDO inhibition might enhance the efficacy of cancer treatment. Indeed result from in vitro and in vivo experiment have suggested an improvement of the efficacy of therapeutic vaccination or chemotherapy by concomitant administration of an IDO inhibitor thus highlighting IDO as an attractive target. Although there have been a number of reports on the development of IDO inhibitors, new types of IDO inhibitors having improved pharmacological properties remain to be discovered.
机译：吲哚胺2，3-二加氧酶（IDO）是一种肝外含血红素的双加氧酶，可催化色氨酸（Trp）吲哚环的C-2 / C-3键上的氧加成。这是必不可少的氨基酸Trp沿犬尿氨酸途径分解为N-甲酰基犬尿氨酸的代谢的初始步骤和限速步骤，这是从头合成生物的途径，导致了NAD。 T细胞淋巴细胞对Trp短缺极为敏感，导致Trp淋巴细胞在G1中经历细胞周期停滞，并导致凋亡和免疫抑制。胎盘对Trp的降解会抑制T细胞增殖，从而防止肿瘤或胎儿的免疫排斥。 IDO在免疫系统内的细胞中普遍表达，但主要在炎症因子中的树突状细胞和巨噬细胞中被细胞因子特异性诱导。众所周知，IDO在多种疾病中过表达，包括癌症，阿尔茨海默氏病，与年龄有关的白内障和HIV脑炎。最近的研究表明，IDO抑制可能会增强癌症治疗的功效。确实来自体外和体内实验的结果表明，通过同时施用IDO抑制剂可以提高治疗性疫苗接种或化学疗法的功效，从而突显IDO作为有吸引力的靶标。尽管已经有许多关于IDO抑制剂开发的报道，但是仍有待发现具有改善的药理特性的新型IDO抑制剂。

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