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Janus激酶:自身免疫性疾病治疗的理想靶点。

Janus kinases: an ideal target for the treatment of autoimmune diseases.

作者信息

Gadina Massimo

机构信息

Translational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, USA.

出版信息

J Investig Dermatol Symp Proc. 2013 Dec;16(1):S70-2. doi: 10.1038/jidsymp.2013.29.

Abstract

Cytokines have pivotal roles in the maintenance of an appropriate immune response. Targeting cytokine receptors has been an effective means of treating immune-related disorders. In the past few years, research efforts have been directed toward cytokines' intracellular signaling pathways and, in particular, the JAK-STAT (Janus kinase-signal transducers and activation of transcription) signaling cascade. Recently, spearheaded by the development of effective drugs in cancer treatment, it has become clear that the targeting of intracellular protein kinases is a very attractive and feasible possibility for the treatment of autoimmune disorders. The targeting of the Janus kinases (JAKs) has been quite successful and two JAK inhibitors are now approved to be used in humans. Interestingly, although some of the inhibitors developed and tested to date have been shown to target more than one kinase, this promiscuity does not appear to be problematic. Novel second-generation, more specific inhibitors are under development, and in the next few years, we expect this class of drugs to become a powerful tool in the hands of clinician treating autoimmune diseases.

摘要

细胞因子在维持适当的免疫反应中起着关键作用。靶向细胞因子受体一直是治疗免疫相关疾病的有效手段。在过去几年中,研究工作一直致力于细胞因子的细胞内信号通路,特别是JAK-STAT(Janus激酶-信号转导子和转录激活子)信号级联反应。最近,在癌症治疗中有效药物开发的引领下,很明显靶向细胞内蛋白激酶对于治疗自身免疫性疾病是一种非常有吸引力且可行的可能性。靶向Janus激酶(JAKs)已经相当成功,现在有两种JAK抑制剂被批准用于人类。有趣的是,尽管迄今为止开发和测试的一些抑制剂已被证明可靶向多种激酶,但这种多靶点特性似乎并无问题。新型第二代、更具特异性的抑制剂正在研发中,在未来几年,我们预计这类药物将成为临床医生治疗自身免疫性疾病的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14c8/4181323/ebf3ff3fce06/nihms631974f1.jpg

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