Molecular basis for the development of novel STAT3 inhibitors

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: University of Shizuoka
• Principal Investigator: Asai Akira 静岡県立大学, 薬学研究院, 教授 (60381737)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: STAT3 / SH2 / シグナル伝達 / 免疫チェックポイント / IDO1 / PD-L1 / 抗がん

Outline of Final Research Achievements

We previously discovered a novel STAT3 inhibitor, STX-COMP, which is expected to be a new anticancer drug candidate. The investigation on the mode of action of STX-COMP and identification of its susceptibility factors are important issues for the purpose of clinical use of this unique compound in future. In this study, we demonstrated STX-COMP inhibits STAT3 dimerization and thereby suppress the transcriptional activity in cancer cells. The profile of this compound in the various bioassays was proved to be quite different from other known STAT3 inhibitors. Furthermore, we revealed that STX-COMP not only inhibited the growth of cancer cells but also suppressed the expression of immune checkpoint factors such as PD-L1 and IDO1 in cancer cells. To identify the biomarker for STX-COMP, we refined the susceptibility factor candidates to the STAT3 inhibition by using the siRNA library. The kinase inhibitors that might be useful for the combination therapies with STX-COMP were also discovered.

Free Research Field

抗がん剤探索