2020 Fiscal Year Final Research Report
Identification of novel compounds from original chemical libraries affecting autoimmune diseases.
| Project/Area Number |
18K06895
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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 48030:Pharmacology-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
Yonezawa Tomo 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (60515964)
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| Co-Investigator(Kenkyū-buntansha) |
倉田 里穂 大阪薬科大学, 薬学部, 助教 (70711729)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 自己免疫疾患 / NFkB / IRF / SEAP / HTS / IL-18 |
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| Outline of Final Research Achievements |
We recently have established the cells stably expressing IRF- or NFkB-driven human secreted embryonic alkaline phosphatase (SEAP) by episomal vector, which can maintain constructs synchronized to host cell replication. We also introduced an another construct stably expressing two IL-18 receptor sub units and then, can monitor IL-18 specifically activated NFkB. Then, we demonstrated high-throughput screening by the novel reporter cells from natural extracts, which are derived from Chinese herb medicine plants, fungi or marine bacteria, or synthetic compounds, which are gifted from Japanese organic synthetic chemists. Finally, we identified several extracts and compounds affecting IRF- or NFkB-activation.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
培養細胞へエピソーマル型ベクターを用いて、恒常的に、NFkBまたはIRF制御下でSEAPを発現および分泌するリポーターを導入し、新規リポーター細胞を樹立し、ドラッグスクリーニングが可能な高感度および確度を持つ測定系を実現した。さらに、樹立したNFkB-SEAPリポーター細胞へ、IL-18受容体遺伝子を同様に導入し、IL-18特異的なNFkBを検出できるリポーター細胞およびアッセイ系も樹立した。最終的に、樹立したリポーター細胞を用いたドラッグスクリーニングにより、独自ライブラリーから薬効を保持する抽出物および化合物を同定した。抗がん剤および自己免疫疾患の治療薬創出に繋がる有意義な結果である。
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