Allosteric inhibitors of the STAT3 signaling pathway

Junhong Qin; Xiaofei Shen; Jian Zhang; Da Jia

doi:10.1016/j.ejmech.2020.112122

Allosteric inhibitors of the STAT3 signaling pathway

Eur J Med Chem. 2020 Mar 15:190:112122. doi: 10.1016/j.ejmech.2020.112122. Epub 2020 Feb 7.

Authors

Junhong Qin¹, Xiaofei Shen², Jian Zhang³, Da Jia⁴

Affiliations

¹ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China.
² Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China. Electronic address: szx379@126.com.
³ Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China.
⁴ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China. Electronic address: Jiada@scu.edu.cn.

PMID: 32066011
DOI: 10.1016/j.ejmech.2020.112122

Abstract

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.

Keywords: Allosteric inhibitors; Autoimmune/inflammatory diseases; Cancer; STAT3.

Publication types

Review

MeSH terms

Allosteric Site
Humans
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
STAT3 Transcription Factor / antagonists & inhibitors*
STAT3 Transcription Factor / chemistry
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects*

Substances

Protein Kinase Inhibitors
STAT3 Transcription Factor
STAT3 protein, human