a Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University , Hangzhou , Zhejiang Province , China.
b Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University , Hangzhou , Zhejiang Province , China.
Expert Opin Ther Pat. 2019 Feb;29(2):137-149. doi: 10.1080/13543776.2019.1567713. Epub 2019 Jan 22.
Tyrosine kinase 2 (Tyk2) is a non-receptor tyrosine-protein kinase, an enzyme that in humans is encoded by the TYK2 gene. Tyk2, together with three other family subtypes, namely, Jak1, Jak2, and Jak3, belong to the JAK family. Before 2014, far more publications and patents appeared in public domain attributing to the development of selective Jak2 and Jak3 inhibitors than those for selective Tyk2 and Jak1 inhibitors.
This review sought to give an overview of patents related to small molecule selective Tyk2 inhibitors published from 2015 to 2018. The article also covers clinical activities of small molecule selective Tyk2 inhibitors in recent years.
As a key component of the JAK-STAT signaling pathway, Tyk2 regulates INFα, IL12, and IL23. Selective inhibition of Tyk2 can provide pharmacological benefits in the treatment of many diseases such as psoriasis, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), cancer, and diabetes. The selectivity against other Jak family subtypes (such as Jak2) is crucial in order to minimize the potential side effects and to maximize the desired pharmacological effects. In this context, this review of recent selective Tyk2 inhibitor patents may prove valid, interesting, and promising within the therapeutic paradigm.
酪氨酸激酶 2(Tyk2)是一种非受体酪氨酸蛋白激酶,在人类中由 TYK2 基因编码。Tyk2 与另外三种家族亚型 Jak1、Jak2 和 Jak3 一起属于 JAK 家族。在 2014 年之前,与选择性 Jak2 和 Jak3 抑制剂的开发相比,公开领域中出现了更多的出版物和专利,归因于选择性 Tyk2 和 Jak1 抑制剂的发展。
本综述旨在概述 2015 年至 2018 年期间发表的与小分子选择性 Tyk2 抑制剂相关的专利。本文还涵盖了近年来小分子选择性 Tyk2 抑制剂的临床活性。
作为 JAK-STAT 信号通路的关键组成部分,Tyk2 调节 INFα、IL12 和 IL23。选择性抑制 Tyk2 可以在治疗许多疾病方面提供药理学益处,如银屑病、系统性红斑狼疮(SLE)、炎症性肠病(IBD)、类风湿关节炎(RA)、癌症和糖尿病。针对其他 Jak 家族亚型(如 Jak2)的选择性至关重要,以最小化潜在的副作用并最大限度地发挥所需的药理学作用。在这种情况下,对最近的选择性 Tyk2 抑制剂专利的审查可能在治疗范例中被证明是有效、有趣和有前途的。