Kinase inhibitors in the treatment of immune-mediated disease.

F1000 medicine reports Pub Date : 2012-01-01 Epub Date: 2012-03-01 DOI:10.3410/M4-5
Apostolos Kontzias, Arian Laurence, Massimo Gadina, John J O'Shea
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引用次数: 58

Abstract

Protein kinases are fundamental components of diverse signaling pathways, including immune cells. Their essential functions have made them effective therapeutic targets. Initially, the expectation was that a high degree of selectivity would be critical; however, with time, the use of "multikinase" inhibitors has expanded. Moreover, the spectrum of diseases in which kinase inhibitors are used has also expanded to include not only malignancies but also immune-mediated diseases. At present, thirteen kinase inhibitors have been approved in the United States, all for oncologic indications. However, there are a growing number of molecules, including several Janus kinase inhibitors, that are being tested in clinical trials for autoimmune diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel diseases. It appears likely that this new class of immunomodulatory drugs will have a major impact on the treatment of immune-mediated diseases in the near future.

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激酶抑制剂治疗免疫介导的疾病。
蛋白激酶是包括免疫细胞在内的多种信号通路的基本组成部分。它们的基本功能使它们成为有效的治疗靶点。最初,人们的期望是高度的选择性至关重要;然而,随着时间的推移,“多激酶”抑制剂的使用范围已经扩大。此外,使用激酶抑制剂的疾病范围也已扩大,不仅包括恶性肿瘤,还包括免疫介导的疾病。目前,13种激酶抑制剂已在美国获得批准,全部用于肿瘤学适应症。然而,越来越多的分子,包括几种Janus激酶抑制剂,正在类风湿性关节炎、银屑病和炎症性肠病等自身免疫性疾病的临床试验中进行测试。在不久的将来,这类新的免疫调节药物可能会对免疫介导疾病的治疗产生重大影响。
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