| Project/Area Number |
18K06694
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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 47040:Pharmacology-related
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| Research Institution | Doshisha Women's College of Liberal Arts (2020)
Osaka University of Pharmaceutical Sciences (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
福永 理己郎 大阪薬科大学, 薬学部, 教授 (40189965)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ERK1/2 / MNK1/2 / がん / 糖尿病 / 脂肪細胞 / NLRP3 / ERK5 / 炎症 / ERK-MAPキナーゼ / p38-MAPキナーゼ / Mnkキナーゼ / BRAF / MEK阻害剤 / HDAC阻害剤 / ERK / MNK / キナーゼ阻害剤 / シグナル伝達 / ERK-MAP kinase |
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| Outline of Final Research Achievements |
We have clarified the possibility of effective drug treatment using MEK inhibitors, which are specific blockers of the ERK pathway, for cancer cells and hypertrophic adipocytes with constitutive activation of the ERK pathway.
In this study, we focused on the MNK kinase downstream of the ERK pathway and the NLRP3 molecule forming inflammasome, which was found to be the target gene of the ERK pathway, as new therapeutic targets. Finally, we found that the combination treatment of an MNK inhibitor called MNK-I1 and an HDAC inhibitor shows a remarkable cell death-inducing effect on some cancer cells having BRAF active mutations. In addition, we found a new drug comparable to a MEK inhibitor that suppresses NLRP3 induction in 3T3-L1 adipocytes stimulated by TNFα.
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| Academic Significance and Societal Importance of the Research Achievements |
1)BRAFやRASという分子の活性変異を有することでERK経路という細胞内シグナルが恒常的に活性化している、がんの薬物治療に対して新たな知見が得られた。すなわち、現在は固形がんへの使用が未承認であるHDAC阻害剤という抗がん剤を、今回明らかにしたMNKという酵素阻害剤と併用することで新たな固形がん治療法につながる可能性がある。
2)脂肪細胞において、炎症にかかわるNLRP3という分子の発現誘導を抑制することのできる新しい薬物ソースを発見したことから、糖尿病などの肥満関連疾患の新たな治療薬の候補に繋がる可能性がある。
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