The discovery of cytokines as key drivers of immune-mediated diseases has spurred efforts to target their associated signalling pathways. Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines, and small-molecule inhibitors of JAKs (jakinibs) have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. Building on the clinical success of first-generation jakinibs, second-generation compounds that claim to be more selective are currently undergoing development and proceeding to clinical trials. However, important questions remain about the advantages and limitations of improved JAK selectivity, optimal routes and dosing regimens and how best to identify patients who will benefit from jakinibs. This Review discusses the biology of jakinibs from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents and the use of jakinibs in a spectrum of immune and inflammatory diseases.

中文翻译：

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抑制JAK作为免疫和炎性疾病的治疗策略

细胞因子作为免疫介导疾病的关键驱动因素的发现刺激了针对其相关信号通路的努力。Janus激酶（JAKs）是许多促炎性细胞因子下游的重要信号传导介质，JAK（jakinibs）的小分子抑制剂已作为治疗炎症驱动的病理学（如类风湿性关节炎，牛皮癣和风湿病）的安全有效选择而受到关注。炎症性肠病。以第一代雅各布尼的临床成功为基础，声称具有更高选择性的第二代化合物目前正在开发中，并正在进行临床试验。但是，关于提高JAK选择性的优势和局限性，仍然存在一些重要的问题，最佳途径和给药方案，以及如何最好地确定将受益于jakinibs的患者。这篇综述从翻译的角度讨论了雅各布尼的生物学，重点是来自临床试验的最新见解，新型药物的开发以及雅各布尼在多种免疫和炎性疾病中的用途。