2014 Fiscal Year Final Research Report
Development of SPAK kinase inhibitors
| Project/Area Number |
25670406
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
UCHIDA SHINICHI 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (50262184)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 高血圧 / 創薬 |
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| Outline of Final Research Achievements |
WNK- STE20/SPS1-related proline-alanine-rich protein kinase (SPAK)-SLC12a transporters cascade regulates blood pressure through NaCl reabsorption in kidney and vasoconstriction. Therefore, drugs that inhibit this signal cascade could become new antihypertensive drugs that have dual effects as a diuretic and vasodilator. We sought to discover SPAK kinase inhibitors by screening chemical compounds and existing drugs. We developed a new screening system using enzyme-linked immunosorbent assay (ELISA) and screened over 20,000 small-molecule compounds. As a result of this screening effort, we discovered one small-molecule compound and Closantel, an antiparasitic agent, which inhibited SPAK-regulated NCC and NKCC1 phosphorylation and activation not only in vitro but also in cultured cell lines and in mice.
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| Free Research Field |
腎臓内科学
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