| Project/Area Number |
23659439
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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, 大学院・医歯学総合研究科, 准教授 (50262184)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 水 / 電解質代謝学 / リン酸化酵素 / ケミカルライブラリー / 高血圧 / キナーゼ |
|---|
| Research Abstract |
We focused on the With-no-lysine kinases (WNK) signaling cascade which has a pivotal role in regulating blood pressure. Agents that inhibit this signal cascade could be a new class of antihypertensive drugs. We sought to discover inhibitors of WNK-SPAK binding by screening chemical compounds that disrupt the binding. For this purpose, we developed a high-throughput screening method using fluorescent correlation spectroscopy. As a result of screening 17,000 compounds, we discovered two novel compounds that reproducibly disrupted the binding of WNK to SPAK. We then performed the modification of the seed compounds, and obtained novel compounds that exhibit the higher inhibitory activity.
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