贾纳斯激酶
JAK-STAT信号通路
鲁索利替尼
癌症研究
锡克
托法替尼
斯达
酪氨酸激酶2
酪氨酸激酶
STAT蛋白
激酶
车站3
信号转导
免疫系统
免疫学
医学
生物
受体
细胞生物学
血小板源性生长因子受体
生长因子
内科学
骨髓
骨髓纤维化
类风湿性关节炎
作者
Pei Shen,Yezhi Wang,Xiangxiang Jia,Pengfei Xu,Lian Qin,Xi Feng,Zhiyu Li,Zhixia Qiu
标识
DOI:10.1016/j.ejmech.2022.114551
摘要
Janus kinases (JAKs) are the non-receptor tyrosine kinases covering JAK1, JAK2, JAK3, and TYK2 which regulate signal transductions of hematopoietic cytokines and growth factors to play essential roles in cell growth, survival, and development. Dysregulated JAK activity leading to a constitutively activated signal transducers and activators of transcription (STAT) is strongly associated with immune-related diseases and cancers. Targeting JAK to interfere the signaling of JAK/STAT pathway has achieved quite success in the treatment of these diseases. However, inadequate clinical response and serious adverse events come along by the treatment of monotherapy of JAK inhibitors. With better and deeper understanding of JAK/STAT pathway in the pathogenesis of diseases, researchers start to show huge interest in combining inhibition of JAK and other oncogenic targets to realize a broader regulation on pathological processes to block disease development and progression, which has hastened extensive research of dual JAK inhibitors over the past decades. Until now, studies of dual JAK inhibitors have added BTK, SYK, FLT3, HDAC, Src, and Aurora kinases to the overall inhibitory profile and demonstrated significant advantage and superiority over single-target inhibitors. In this review, we elucidated the possible mechanism of synergic effects caused by dual JAK inhibitors and briefly describe the development of these agents.
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