2002 Fiscal Year Final Research Report Summary
Development of novel anti-atheroscleroic agents
| Project/Area Number |
12557220
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | Kumamoto University |
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Principal Investigator |
NAKAYAMA Hitoshi Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (70088863)
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| Co-Investigator(Kenkyū-buntansha) |
KUNIYASU Akihiko Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (90241348)
MIYAZAKI Akira Showa University, School of Medicine, Professor, 医学部, 教授 (70253721)
ISHIZUKA Tadao Kumamoto University, Graduate School of Medical and Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (60176203)
SANNO-HE Kunio Mitsui Chemical Co., Institute for Material Sciences, Team Leader, マテリアルサイエンス研究所, 計算科学室長
NISHI Takao Ohtsuka Pharmaceutical Co., Section of Medical Creation, Team Leader, 徳島第2工場・医薬生産部研究室, 室長
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| Project Period (FY) |
2000 – 2002
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| Keywords | sulfonylurea / glibenclamide / macrophage / CD36 / ACAT inhibitors / cholesterol metabolism / scavenger receptors |
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| Research Abstract |
We have found that glibendamide, a typical antidiabetic sulfonylurea, inhibits acyl CoA:cholesterol acyllransferase (ACAT) that plays a crucial role to esterify the intracellular free cholesterol and a trigger to form foamed cells in macrophage. In this project we aim to develop novel ACAT inhibitors that are distinct from conventional ones in chemical structures and properties, because the conventional drug candidates of chemically neutral in charge are worried about their adverse effects on adrenal grand. During the passed three years, we organized a team of bioorganic chemist, synthetic organic chemist, molecular pharmacologist, and professionals in in vivo evaluation of drugs, and incomputer-aided drug design. We are succeeded in creating several drug candidates that are eliminated inslin secrition activity and have unique characteristics for ACAT inhibition in term of selective deliverly to taget cells and organs. The compounds are preparing for the patents and we will open the detailed information after the patent issue is completed.
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