| Project/Area Number |
18K05364
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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 37030:Chemical biology-related
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| Research Institution | Hyogo Medical University (2023)
Hyogo University of Health Sciences (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山下 政克 愛媛大学, 医学系研究科, 教授 (00311605)
田中 明人 兵庫医療大学, 薬学部, 教授 (30454789)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | アレルギー / 低分子化合物 / アフィニティ樹脂 / Rab |
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| Outline of Final Research Achievements |
SH-2251 is a small molecule compound that potently inhibits IL-5 production from Th2 cells and is effective in vivo, but the mechanism was unknown. Specific binding proteins Rab1A, 1B, 5C, 8, 11B, 35, 10 and 12 were identified using the proprietary affinity resin AquaFirmus, and specificity and affinity (0.28-1.3 nM) were confirmed by Western blotting or biacore. Using overexpressing or knouckdown techniques of Rabs in cells, changes of IL-5 production and the effects of the compounds on IL-5 production were investigated, but no clear conclusions could be drawn. During synthetic development of more effective compounds, it is considered that the linker addition part used in the target search was also important, thus, a new target is currently being found.
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| Academic Significance and Societal Importance of the Research Achievements |
我が国の約2人に1人が何らかのアレルギー疾患に罹患しており、アレルギー性鼻炎、花粉症や気管支喘息の患者は多い。抗ヒスタミン剤、Th2細胞性炎症に対してはステロイドが主に用いられ、近年、重症患者にはヒト化モノクローナル抗体(ヌーカラ、ゾレア、デュピクセント等）が続々と上市されているが、生物製剤のため、高価な注射剤であり、利用しづらい。この様にアレルギー疾患の根治に繋がる低分子化合物の開発研究は未だ立ち後れた状態にある中、SH2251はTh2細胞への分化を抑制してIL-5産生を抑制し、in vivoモデルにも有効性を示す、有望な低分子化合物で、メカニズム解明や化合物合成展開には意義がある。
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