[治疗皮肤病的 Janus 激酶抑制剂]。

Dermatologie (Heidelberg, Germany) Pub Date : 2024-10-01 Epub Date: 2024-08-30 DOI:10.1007/s00105-024-05406-8
Farzan Solimani, Kamran Ghoreschi
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引用次数: 0

摘要

干扰素ɣ和白细胞介素 4 等免疫因子属于细胞因子,它们的信号传输依赖于 I/II 型受体。激活后,这些受体将信号传递到细胞核,从而通过由 Janus 激酶(JAK)组成的信号级联调节基因转录。这个由四种激酶(JAK 1、JAK 2、JAK 3 和酪氨酸激酶 2 (TYK2))组成的家族随后会激活信号转导和转录激活因子(STAT)的成员。这一发现将 JAK/STAT 信号通路变成了治疗利用 I/II 型受体的细胞因子起致病作用的炎症性疾病的药理靶点。2018 年,欧洲药品管理局(EMA)批准托法替尼用于治疗银屑病关节炎。这是 JAK/STAT 通路抑制剂首次获批用于皮肤科和风湿科医生治疗的患者。此后,又有几种新的 JAK 抑制剂获批用于特应性皮炎、斑秃、白癜风和斑块型银屑病等皮肤病的治疗。此外,目前正在研究 JAK 抑制剂用于治疗许多其他皮肤病。因此,与单克隆抗体相比,全身性 JAK 抑制剂以更广泛的免疫学方法完善了免疫疗法的范围。JAK 抑制剂的分子量较低,可以制备成全身用药和局部用药。使用这些药物可以替代局部类固醇。必须考虑到 JAK 抑制剂的安全性。在未来几年中,可能出现的长期影响将逐渐显现。本文介绍了已获批准的 JAK 抑制剂和相关的新型 JAK 抑制剂,它们都是有望获准作为皮肤科治疗药物的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Janus kinase inhibitors for skin disorders].

Immune factors such as interferon‑ɣ and interleukin 4 belong to the group of cytokines that are dependent on type I/II receptors for their signal transmission. Upon activation, these receptors transmit their signal to the cell nucleus and, thus, modulate gene transcription via a signaling cascade consisting of Janus kinases (JAK). This family of four kinases (JAK 1, JAK 2, JAK 3, and tyrosine kinase 2 (TYK2)) subsequently activate members of the signal transducer and activator of transcription (STAT). This finding turned the JAK/STAT signaling pathway into a pharmacological target for the treatment of inflammatory diseases in which cytokines using type I/II receptors play a pathogenic role. In 2018, the European Medicines Agency (EMA) approved tofacitinib for the treatment of psoriatic arthritis. This was the first approval of a JAK/STAT pathway inhibitor for patients treated by dermatologists and rheumatologists. Since then, several new JAK inhibitors have been approved for dermatologic diseases such as atopic dermatitis, alopecia areata, vitiligo, and plaque-type psoriasis. In addition, JAK inhibitors are being investigated for the treatment of many other skin diseases. Thus, systemic JAK inhibitors complete the spectrum of immunotherapeutics with a broader immunological approach compared to monoclonal antibodies. The low molecular weight of JAK inhibitors enables the preparation of these drugs for both systemic and topical administration. Their utilization could represent a valuable alternative to topical steroids. The safety profile of JAK inhibitors must be taken into account. Possible long-term effects may become apparent in the next few years. This article describes both approved JAK inhibitors and relevant new JAK inhibitors that are promising candidates for approval as therapeutics in dermatology.

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