| Project/Area Number |
15K07900
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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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| Research Field |
Physical pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Toyooka Naoki 富山大学, 大学院理工学研究部, 教授 (10217565)
SASAOKA Toshiyasu 富山大学, 大学院医学薬学研究部, 教授 (00272906)
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| Research Collaborator |
UMEDA Tomonobu
TANAKA Nobutada
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | SHIP2 / 阻害剤 / イン・シリコスクリーニング / 分子ドッキング計算 / 相互作用エネルギー計算 / 糖尿病 / インスリン / アルツハイマー型認知症 / インシリコスクリーニング / ファーマコフォア / 結合自由エネルギー計算 / ドラッグデザイン |
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| Outline of Final Research Achievements |
Inhibitors of SHIP2 (SH2 domain-containing inositol 5’-phosphatase 2) are considered to have great potential of treating type 2 diabetes accompanying dementia of Alzheimer's type. In this study, we first identified two novel inhibitors of SHIP2 using in silico screening, in vitro assay for detecting SHIP2 inhibition, and cell based assay for evaluating effect on insulin signaling. These two inhibitors were found to possess more potent SHIP2 inhibitory activities than those of known inhibitors such as AS1949490 and CPDA. We next constructed docking models of two new inhibitors with SHIP2 and evaluated interaction energies using quantum mechanics-based method. It was suggested that these inhibitors could form more stable hydrogen bonds with SHIP2 than CPDA, which would contribute their more potent inhibitory activities.
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