Novel imidazopyridine suppresses STAT3 activation by targeting SHP-1

Journal of Enzyme Inhibition and Medicinal Chemistry

Chuan-Hsun Chang¹  Szu-Hsien Wu²  Chung-Wai Shiau³  Jung-Chen Su⁴ 

[1] Chairman of the Surgical Department, Cheng Hsin General Hospital, Taipei, Taiwan;Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan;Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan;Department of Chemistry, Chung-Yuan Christian University, Chungli, Taiwa;Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan;Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan;

关键词: STAT3;    SHP-1;    HCC;    imidazopyridine;   

DOI  :  10.1080/14756366.2018.1497019

来源: publisher

【 摘 要 】

The unregulated activation of STAT3 has been demonstrated to occur in many cancers and enhances tumour growth, migration, and invasion. Stimulation by cytokines, growth factors, and hormones triggers this activation by phosphorylating STAT3 at tyrosine 705. Novel imidazopyridine compounds were synthesized to evaluate the inhibition of STAT3 at Y705. Among the tested compounds, 16 reduced the level of phospho-STAT3, inhibited the downstream signalling cascade and subsequently attenuated the survival of hepatocellular carcinoma (HCC) cells. Further assays showed that the reduction effects of compound 16 on tyrosine 705 of STAT3 were attributed to up-regulation of protein tyrosine phosphatase SHP-1.

【 授权许可】

CC BY