Norman Consulting , 18 Pink Lane, Burnham, Bucks, SL1 8JW , UK
Expert Opin Ther Pat. 2014 Sep;24(9):979-91. doi: 10.1517/13543776.2014.936381. Epub 2014 Jul 3.
The non-receptor tyrosine kinase, inducible tyrosine kinase (Itk), plays an important role in thymus(T)-cell signalling and the production of pro-inflammatory cytokines. Itk, and the other Tec family members, Rlk and Tec, are viewed as attractive drug targets for new agents for the treatment of autoimmune and inflammatory diseases. Interest in Itk inhibitors is still modest compared to other kinases such as the Janus kinase (JAK) family or Syk.
This article reviews the patent filings published from January 2010 to April 2014 that claim Itk inhibitors. It first considers those applications that claim selective, or apparently selective, Itk inhibitors. It then considers those applications that claim less-selective Itk inhibitors. The recent interest in irreversible Itk inhibitors is also discussed.
There is a difference of opinion as to the preferred utility for Itk inhibitors. Progress has been made in designing selective Itk inhibitors but little clinical progress. Until clinical data are available, it remains difficult to assess how well Itk inhibitors compare with JAK inhibitors as potential treatments for rheumatoid arthritis. However, animal data suggest that irreversible Itk inhibitors could be useful in treating asthma, whereas dual Itk inhibitors may have more utility in treating rheumatoid arthritis.
非受体酪氨酸激酶,诱导型酪氨酸激酶(Itk),在 T 细胞信号转导和促炎细胞因子的产生中发挥重要作用。Itk 与其他 Tec 家族成员 Rlk 和 Tec 被视为治疗自身免疫和炎症性疾病的新型药物靶点。与 Janus 激酶(JAK)家族或 Syk 等其他激酶相比,人们对 Itk 抑制剂的兴趣仍然不大。
本文回顾了 2010 年 1 月至 2014 年 4 月期间公布的声称具有 Itk 抑制剂活性的专利申请。首先考虑了那些声称具有选择性或明显选择性 Itk 抑制剂的申请。然后考虑了那些声称具有较低选择性的 Itk 抑制剂的申请。还讨论了最近对不可逆 Itk 抑制剂的兴趣。
对于 Itk 抑制剂的首选用途存在不同意见。虽然在设计选择性 Itk 抑制剂方面取得了进展,但在临床方面进展甚微。在获得临床数据之前,仍然难以评估 Itk 抑制剂作为类风湿关节炎潜在治疗药物与 JAK 抑制剂相比的效果如何。然而,动物数据表明,不可逆的 Itk 抑制剂可能在治疗哮喘方面有用,而双重 Itk 抑制剂可能在治疗类风湿关节炎方面更有用。