Allosteric inhibitors of the STAT3 signaling pathway
Allosteric inhibitors of the STAT3 signaling pathway
复制标题
STAT3信号通路的变构抑制剂
DOI：
10.1016/j.ejmech.2020.112122
复制
发表时间：
2020
影响因子：
6.7
通讯作者：
Da Jia
中科院分区：
文献类型：
--
作者：
Junhong Qin;Xiaofei Shen;Jian Zhang;Da Jia
信号转导子和转录激活子 3 (STAT3) 信号传导的过度表达和/或过度激活存在于多种人类疾病中，包括癌症、自身免疫性疾病和炎症性疾病。因此，STAT3代表了治疗这些疾病的一个非常有前景的治疗靶点。然而，传统的 STAT3 正构抑制剂的临床疗效有限，选择性低，副作用较多，并且出现了获得性耐药。针对 STAT3 或其上游分子的变构抑制剂已成为克服这些障碍的有前途的方法。在这篇综述中，我们总结了这些抑制剂的开发及其应用的最新进展。
Over-expression and/or hyperactivation of signal transducer and activator of transcription 3 (STAT3) signaling are found in various human diseases, including cancer, autoimmune disorders, and inflammatory diseases. Therefore, STAT3 represents a highly promising therapeutic target for the treatment of these diseases. However, the traditional orthosteric inhibitors of STAT3 exhibit limited clinical efficacy, with low selectivity, numerous side effects, and emerging acquired resistance. Allosteric inhibitors targeting STAT3 or its upstream molecules have emerged as a promising approach to overcome these barriers. In this review, we summarize the recent advances in the development of these inhibitors as well as their applications.