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吲哚胺 2,3-双加氧酶抑制剂:新型专利先导化合物综述。

Inhibitors of indoleamine 2,3-dioxygenase: a review of novel patented lead compounds.

机构信息

Istituto Superiore di Sanità, Department of Cell Biology and Neurosciences, Rome, Italy.

出版信息

Expert Opin Ther Pat. 2010 Feb;20(2):229-50. doi: 10.1517/13543770903512974.

Abstract

IMPORTANCE OF THE FIELD

The enzyme indoleamine 2,3-dioxygenase (IDO) regulates immune responses through the capacity to degrade the essential amino-acid tryptophan into kynurenine and other downstream metabolites that suppress effector T-cell function and favour the differentiation of regulatory T cells. The current experimental evidence indicates that IDO can be expressed by a variety of cell types, including dendritic cells, tumour cells and stromal cells. Recently, IDO has been implicated in B-cell stimulation and autoantibody production in experimental models of autoimmune diseases.

AREAS COVERED IN THIS REVIEW

Advances in the biochemistry of IDO and our understanding of the biological relevance of IDO-mediated tryptophan consumption to the establishment of immune tolerance are summarised and discussed. A selection of recent patents in the field are also reviewed and analysed.

WHAT THE READER WILL GAIN

Readers will gain an overview of the patented compounds with IDO inhibitory activity from an immunologist's perspective. They will also learn about the companies that are main players in the field.

TAKE HOME MESSAGE

Current evidence points to IDO as a molecular target for therapeutic intervention in order to restrain unwanted inflammatory/autoimmune responses and/or to boost antitumour immunity.

摘要

重要性领域

酶吲哚胺 2,3-双加氧酶(IDO)通过降解必需氨基酸色氨酸为犬尿氨酸和其他下游代谢物的能力来调节免疫反应,这些代谢物抑制效应 T 细胞功能并有利于调节性 T 细胞的分化。目前的实验证据表明,IDO 可以由多种细胞类型表达,包括树突状细胞、肿瘤细胞和基质细胞。最近,IDO 已被牵涉到自身免疫性疾病的实验模型中的 B 细胞刺激和自身抗体产生。

本综述涵盖的领域

总结和讨论了 IDO 生化方面的进展以及 IDO 介导的色氨酸消耗对免疫耐受建立的生物学相关性的理解。还对该领域的一些最新专利进行了选择和分析。

读者将获得什么

读者将从免疫学家的角度获得具有 IDO 抑制活性的专利化合物的概述。他们还将了解该领域的主要参与者的公司。

带回家的信息

目前的证据表明 IDO 是治疗干预的分子靶点,以抑制不必要的炎症/自身免疫反应和/或增强抗肿瘤免疫。

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