The many faces of Janus kinase
The many faces of Janus kinase
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DOI：
10.1016/j.bcp.2011.12.024
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Dobrzanski, Pawel
中科院分区：
文献类型：
--
作者：
Seavey, Matthew M.;Dobrzanski, Pawel
Janus激酶已被证明在许多免疫过程中是必不可少的，但越来越多的证据表明，它们也在许多疾病的发病机制中发挥关键作用，包括炎症性疾病和癌症，它们促进肿瘤发生的多个步骤。几家公司正在开发JAK激酶抑制剂的晚期临床计划，第一种小分子JAK抑制剂Jakafi(R)(Ruxolitinib)刚刚被批准用于治疗骨髓增殖性肿瘤。其他几种分子正在崛起，用于治疗关节炎、牛皮癣和多种癌症。这篇评论将提供JAK(激酶)领域的回顾，因为它与用于治疗癌症和自身免疫性疾病的小分子抑制有关，重点是JAK2。将讨论JAK的实验和临床抑制剂在实体肿瘤和血液系统恶性肿瘤、狼疮、关节炎、结肠炎、神经疾病、疼痛、糖尿病和心血管疾病中的使用。此外，它还将回顾目前该领域的范例和治疗方案，这些方案可以由Janus激酶的小分子抑制剂来补充。(C)2011 Elsevier Inc.保留所有权利。
Janus kinases have proved to be essential for many immunological processes but there is growing evidence that they also play a critical role in pathogenesis of many diseases including inflammatory diseases and cancer where they promote multiple steps of tumorigenesis. Several companies are in late stage clinical programs for the development of JAK kinase inhibitors and the first small molecule JAK inhibitor, Jakafi (R) (ruxolitinib) has been just approved for treatment of myeloproliferative neoplasms. Several other molecules are on the rise to treat arthritis, psoriasis and multiple types of cancer. This commentary will provide a review of the JAK(kinase field as it pertains to small molecule inhibition for the treatment of cancer and autoimmune diseases with an emphasis on JAK2. The use of experimental and clinical inhibitors of JAK will be discussed for solid tumor and hematological malignancies, lupus, arthritis, colitis, neurological disorders, pain, diabetes and cardiovascular disease. In addition, it will review current paradigms in the field and treatment programs which could be complemented by small molecule inhibitors of Janus kinase. (C) 2011 Elsevier Inc. All rights reserved.