Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Rheumatology (Oxford). 2024 Feb 1;63(2):298-308. doi: 10.1093/rheumatology/kead448.
Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib.
Janus 激酶（JAKs）是一类胞质酪氨酸激酶，可调节细胞因子信号转导，包括涉及多种炎症性疾病的细胞因子，如类风湿关节炎、银屑病、特应性皮炎和炎症性肠病。目前已有几种小分子 JAK 抑制剂（JAKi）获批用于治疗各种免疫介导的炎症性疾病。然而，这些药物之间存在关键差异，这可能会转化为独特的临床特征。每种 JAKi 都具有独特的化学结构，导致其在靶 JAK 的催化裂隙内以独特的结合模式结合，并产生不同的药理学特征。此外，现有的药物对 JAK 同工型的选择性不同，以及针对非 JAK 的脱靶效应也不同。其他差异包括对血液学参数、DNA 损伤修复、生殖毒性和代谢/消除的影响。在这里，我们回顾了 JAKi 阿布昔替尼、巴瑞替尼、菲戈替尼、培非替尼、托法替尼和乌帕替尼的药理学特征。
