众多激酶——治疗类风湿关节炎的最佳靶点是哪些？
A multitude of kinases--which are the best targets in treating rheumatoid arthritis?
机构信息
Geriatric Research Education and Clinical Center (GRECC), MC154R, VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.
出版信息
Rheum Dis Clin North Am. 2010 May;36(2):367-83. doi: 10.1016/j.rdc.2010.02.005.
Abstract
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.
摘要
小分子激酶抑制剂在治疗类风湿关节炎（RA）的新药研发中日益占据核心地位。通过靶向激酶，小分子抑制剂可以发挥强大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寻找可用于治疗慢性炎症性疾病（如 RA）的激酶。尽管许多激酶抑制剂已被证明在治疗动物的炎症性关节炎方面有效，但在 RA 临床试验中进行测试的却很少。本文讨论了在 RA 中追求小分子激酶抑制剂的挑战和进展，包括从前驱抑制剂失败中吸取的教训以及首批进入 RA 舞台的抑制剂的前景。
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