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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (3): 323-330.doi: 10.12092/j.issn.1009-2501.2023.03.011

• 综述与讲座 • 上一篇    下一篇

酪氨酸激酶2抑制剂治疗斑块型银屑病机制与临床研究进展

沈嘉庆,刘毅   

  1. 中国医学科学院皮肤病医院,南京 210042,江苏 
  • 收稿日期:2022-11-17 修回日期:2023-01-30 出版日期:2023-03-26 发布日期:2023-04-19
  • 通讯作者: 刘毅,男,副主任医师,硕士研究生导师,主要从事免疫皮肤病相关研究。 E-mail:liuyi@pumcderm.cams.cn
  • 作者简介:沈嘉庆,男,硕士研究生,主要从事免疫皮肤病相关研究。 E-mail:sjq1997may@163.com
  • 基金资助:
    江苏省自然科学基金(BK201256);江苏省研究型医院学会专项科研基金(2022-PF-01-001)

Mechanism of tyrosine kinase 2 inhibitors in treatment of plaque psoriasis and their progress in clinical trials 

SHEN Jiaqing, LIU Yi   

  1. Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, Jiangsu, China 
  • Received:2022-11-17 Revised:2023-01-30 Online:2023-03-26 Published:2023-04-19

摘要: 斑块型银屑病是一种免疫相关的慢性炎症性皮肤病,较为常见,疾病负担重,严重影响患者身心健康。近十余年,生物制剂治疗银屑病取得了突破性进展,但安全高效的靶向口服药物仍有待开发。JAK-STAT信号转导途径通过转导细胞因子信号,在多种免疫相关疾病发生发展中具有重要作用。在 JAK家族成员中,酪氨酸激酶 2已被证实可以通过转导白介素-12/23、干扰素及其下游信号通路,参与斑块型银屑病的发生发展,是较为理想的药物靶点。高度选择性酪氨酸激酶 2抑制剂氘可来昔替尼 III期临床试验显示出良好的疗效和安全性,已获美国食品药品管理局批准用于口服治疗斑块型银屑病,另有多种酪氨酸激酶 2抑制剂目前正在研发中。本文介绍了JAK-STAT通路及酪氨酸激酶 2参与斑块型银屑病发病的机制,及酪氨酸激酶2抑制剂在斑块型银屑病治疗领域的临床试验现状。

关键词: 斑块型银屑病, JAK-STAT通路, 酪氨酸激酶2抑制剂

Abstract: As a chronic, immune-mediated in-flammatory disease, plaque psoriasis has a great burden of disease and influences on patient's physi-cal and mental health. In the past decade, plaque psoriasis treatment with biological agents achieved breakthrough development, while oral drugs with promising efficacy and safety are yet to be met. By cell signal transduction, the Janus kinase-signal transducer and activator of transcription pathway plays an important role in numerous immune-relat-ed diseases. Tyrosine kinase 2 (TYK2), a member of the JAK family, can impact on plaque psoriasis by regulating signaling and functional responses down-stream of IL-12, IL-23, IFN. Deucravacitinib, a highly selective TYK2 inhibitor, has finished its phase 3 clinical trials and shown its efficacy and safety in treatment of plaque psoriasis. Several kinds of TYK2 inhibitors are under research and develop-ment at the moment. In this review, we demon-strate roles of JAK-STAT pathway and TYK2 in plaque psoriasis as well as updates on ongoing and recently completed trials of TYK2 inhibitors. 

Key words: plaque psoriasis, JAK-STAT pathway, tyrosine kinase 2 inhibitor

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