Jakinibs of All Trades: Inhibiting Cytokine Signaling in Immune-Mediated Pathologies.
Jakinibs of All Trades: Inhibiting Cytokine Signaling in Immune-Mediated Pathologies.
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DOI：
10.3390/ph15010048
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发表时间：
2021-12-30
期刊：
影响因子：
--
通讯作者：
Gadina M
中科院分区：
文献类型：
--
作者：
Alexander M;Luo Y;Raimondi G;O'Shea JJ;Gadina M
在过去的25年中，Janus激酶（JAK）的抑制一直被用作治疗各种免疫和炎性疾病的方式。虽然JAK抑制剂（jakinibs）的临床开发始于对其在同种异体移植中的应用的研究，但其最广泛的成功应用来自自身免疫性和过敏性疾病。多个分子现已在全球80个国家被批准用于从类风湿性关节炎和幼年关节炎到溃疡性结肠炎、特应性皮炎、移植物抗宿主病（GVHD）和其他炎性病理的疾病。此外，两种jakinib在治疗住院的冠状病毒病-19（COVID-19）患者中也显示出令人惊讶的疗效，表明jakinib在感染性疾病、细胞因子风暴和其他炎症过度综合征中的额外作用。Jakinibs作为一类药物，随着JAK靶向选择性和器官选择性的发展，其临床应用不断扩大。重要的是，Jakinib的安全性和药代动力学已经与临床开发一起进行了研究，进一步巩固了Jakinib使用的潜在益处和局限性。本次审查涵盖了已批准或正在进行后期研究的jakinibs，重点关注临床应用，药代动力学和安全性特征以及未来的机遇和挑战。
Over the last 25 years, inhibition of Janus kinases (JAKs) has been pursued as a modality for treating various immune and inflammatory disorders. While the clinical development of JAK inhibitors (jakinibs) began with the investigation of their use in allogeneic transplantation, their widest successful application came in autoimmune and allergic diseases. Multiple molecules have now been approved for diseases ranging from rheumatoid and juvenile arthritis to ulcerative colitis, atopic dermatitis, graft-versus-host-disease (GVHD) and other inflammatory pathologies in 80 countries around the world. Moreover, two jakinibs have also shown surprising efficacy in the treatment of hospitalized coronavirus disease-19 (COVID-19) patients, indicating additional roles for jakinibs in infectious diseases, cytokine storms and other hyperinflammatory syndromes. Jakinibs, as a class of pharmaceutics, continue to expand in clinical applications and with the development of more selective JAK-targeting and organ-selective delivery. Importantly, jakinib safety and pharmacokinetics have been investigated alongside clinical development, further cementing the potential benefits and limits of jakinib use. This review covers jakinibs that are approved or are under late phase investigation, focusing on clinical applications, pharmacokinetic and safety profiles, and future opportunities and challenges.
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影响因子：
3.4
作者：
Chimalakonda A;Burke J;Cheng L;Catlett I;Tagen M;Zhao Q;Patel A;Shen J;Girgis IG;Banerjee S;Throup J
通讯作者：
Throup J
DOI：
10.1038/nrneph.2016.41
发表时间：
2016-05
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Braza F;Brouard S;Chadban S;Goldstein DR
通讯作者：
Goldstein DR
影响因子：
27.4
作者：
Alunno, Alessia;Najm, Aurelie;Mariette, Xavier
通讯作者：
Mariette, Xavier
DOI：
10.1124/jpet.114.218164
发表时间：
2014-12-01
影响因子：
3.5
作者：
Coffey, Greg;Betz, Andreas;Sinha, Uma
通讯作者：
Sinha, Uma
影响因子：
2
作者：
Chen, Xuejun;Shi, Jack G.;Yeleswaram, Swamy
通讯作者：
Yeleswaram, Swamy