A Multitude of Kinases-Which are the Best Targets in Treating Rheumatoid Arthritis?
A Multitude of Kinases-Which are the Best Targets in Treating Rheumatoid Arthritis?
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DOI：
10.1016/j.rdc.2010.02.005
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发表时间：
2010-05-01
影响因子：
2.3
通讯作者：
Robinson, William H.
中科院分区：
文献类型：
--
作者：
Lindstrom, Tamsin M.;Robinson, William H.
小分子激酶抑制剂越来越成为类风湿性关节炎（RA）治疗新药的中心。通过靶向激酶，小分子抑制剂可以发挥有效的抗炎和免疫调节作用;小分子激酶抑制剂在癌症治疗中的成功促使人们努力鉴定可以靶向治疗慢性炎症性疾病（如RA）的激酶。虽然许多激酶抑制剂已被证明在治疗动物炎性关节炎中有效，但很少在RA临床试验中进行测试。本文讨论了寻求小分子激酶抑制剂治疗RA的挑战和进展，包括从以前的领跑者抑制剂失败中吸取的教训，以及抑制剂在RA阶段首次亮相的希望。
Small-molecule kinase inhibitors are increasingly taking center stage in the quest for new drugs for the treatment of rheumatoid arthritis (RA). By targeting kinases, small-molecule inhibitors can exert potent anti-inflammatory and immunomodulatory effects; the success of small-molecule kinase inhibitors in the treatment of cancer has spurred efforts to identify kinases that could be targeted for the treatment of chronic inflammatory disorders, such as RA. Although many kinase inhibitors have proved efficacious in the treatment of inflammatory arthritis in animals few have been tested in RA clinical trials. This article discusses the challenges and progress in the pursuit of small-molecule kinase inhibitors for RA, including lessons learned from the failure of erstwhile frontrunner inhibitors and the promise of inhibitors making their debut on the RA stage.