当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small molecules.

Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small molecules.

Abstract：

:STAT3 is an attractive therapeutic target for cancer therapy. However, due to low potency or poor druggability, none of its inhibitors are clinically available. Herein, a series of aminobenzo[b]thiophene 1, 1-dioxides with good drug-likeness properties were designed, synthesized and evaluated as STAT3 inhibitors. Most of them exhibited higher antitumor activity than the small-molecule STAT3 inhibitor, Stattic. Compound 15 was the most potent and had an IC50 range in 0.33-0.75 μM in various cancer cell lines. The overexpressed and IL-6 induced phosphorylation levels of STAT3 were both inhibited by 15 without influencing the phosphorylation levels of the upstream kinases Src and Jak2. 15 also suppressed the expressions of STAT3 downstream gene, Bcl-2. 15 effectively increased the ROS levels of cancer cells, induced cancer cell apoptosis and abolished the colony formation ability of cancer cells without affecting bypass kinase p-Erk. Furthermore, 15in vivo induced significant antitumor responses, and exhibited less toxicity than Doxorubicin. Together, this study described a class of new STAT3 inhibitors as antitumor agents.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang W,Ma T,Li S,Yang Y,Guo J,Yu W,Kong L

doi

10.1016/j.ejmech.2016.09.068

subject

Has Abstract

pub_date

2017-01-05 00:00:00

pages

538-550

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30804-2

journal_volume

125

pub_type

杂志文章

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