2021 Fiscal Year Final Research Report
Inhibition of chronic arthritis and joint destruction by targeting Stat3
| Project/Area Number |
19K09655
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kumamoto University (2020-2021)
Keio University (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 関節リウマチ |
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| Outline of Final Research Achievements |
We screened approximately 4.9 million small compounds as potential inhibitors of Stat3 using in silico screening, and identified 39 candidates as potential Stat3 inhibitors. We then tested available 15 compounds out of 39 their Stat3 inhibiting activity in in vitro secondary screen. We found that 3 out 15 had potential Stat3 inhibiting activities in vitro, thus we analyzed the effects of these 3 compounds in collagen induced arthritis (CIA) model, a rheumatoid arthritis model, in vivo. One out of 3 compounds significantly inhibited arthritis development without apparent adverse effects in CIA models in vivo. Finally, we confirmed that the one compound significantly blocked Stat3 phosphorylation induced by IL-6 in vitro.
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| Free Research Field |
整形外科、血液、膠原病
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| Academic Significance and Societal Importance of the Research Achievements |
関節リウマチ（RA）は慢性的に経過する関節炎や関節破壊のため、ADLやQOLが著しく障害される慢性炎症性疾患である。今日、炎症性サイトカインやシグナル分子であるJakを標的とした分子標的治療が発展しているが、転写因子を標的とした治療法は開発されていない。今回、転写因子であるStat3の阻害によりRAに対する治療効果の可能性を示した点並びにStat3阻害効果をin vivoおよびin vitroで発揮する低分子化合物を同定した点で学術的意義がある。また、既存の治療法では寛解を得られない患者も少なくなく、価格的に安価な低分子化合物で新たな治療法の選択肢を提案した点で社会的意義もあると考えている。
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