Development of drugs targeting secretory inhibition of transthyretin for familial amyloidotic polyneuropathy
| Project/Area Number |
24790079
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
SATO Takashi 熊本大学, 発生医学研究所, 特定事業研究員 (70555755)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | トランスサイレチン / アミロイド / 小胞体 / 小胞体関連分解 / 化合物スクリーニング / 薬理学 |
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| Research Abstract |
The final goal of this study is to develop drug for treatment of Transthyretin (TTR)-Familial Amyloidotic Polyneuropathy (FAP). We previously identified that inhibition of TTR tetramerization in the endoplasmic reticulum that blocks secretion of mutant TTR could be a target of candidate drug for treatment of FAP. In this study, we performed in silico virtual screening of inhibitor for TTR tetramerization. Among 2.5 million compound, we selected about 20 compounds and examined the effect of selected compounds on secretion and tetramerization of mutant TTR. Finally, we identified 2 compounds that reduce secretion of mutant TTR, one of which inhibits tetramerization of mutant TTR. Moreover, to perform high-throughput screening of chemical libraries, we developed a fluorescence-based assay system that monitor TTR tetramerization in vitro and plan to use this system in future study.
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Report
(3 results)
Research Products
(18 results)
