Despite recent advances in the treatment of autoimmune and inflammatory diseases, unmet medical needs in some areas still exist. One of the main therapeutic approaches to alleviate dysregulated inflammation has been to target the activity of kinases that regulate production of inflammatory mediators. Small-molecule kinase inhibitors have the potential for broad efficacy, convenience and tissue penetrance, and thus often offer important advantages over biologics. However, designing kinase inhibitors with target selectivity and minimal off-target effects can be challenging. Nevertheless, immense progress has been made in advancing kinase inhibitors with desirable drug-like properties into the clinic, including inhibitors of JAKs, IRAK4, RIPKs, BTK, SYK and TPL2. This Review will address the latest discoveries around kinase inhibitors with an emphasis on clinically validated autoimmunity and inflammatory pathways.

尽管最近在自身免疫性疾病和炎症性疾病的治疗方面取得了进展，但在某些领域仍然存在未满足的医疗需求。缓解失调炎症的主要治疗方法之一是针对调节炎症介质产生的激酶的活性。小分子激酶抑制剂具有广泛的疗效、便利性和组织渗透性的潜力，因此通常比生物制剂具有重要优势。然而，设计具有靶向选择性和最小脱靶效应的激酶抑制剂可能具有挑战性。尽管如此，在将具有理想药物样特性的激酶抑制剂推进临床方面取得了巨大进展，包括 JAK、IRAK4、RIPK、BTK、SYK 和 TPL2 的抑制剂。