| Project/Area Number |
15H04337
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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 | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
FURUSE Mikio 自然科学研究機構, 生理学研究所・細胞構造研究部門, 教授 (90281089)
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| Research Collaborator |
TENNO Natsuko (GODA Natsuko)
TENNO Takeshi
NODA Shota
HORI Kiminori
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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 |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | PDZドメイン / タンパク質間相互作用阻害薬 / ケミカルバイオロジー / アントラニル酸 / フラボノイド / グリチルリチン / 医薬品吸収促進剤 / バリア強化剤 / タイトジャンクション / Wntシグナル伝達系 / Dishevelled阻害剤 / トリプルネガティブ乳がん / 細胞形態変化 / DVL阻害剤 / タンパク質間相互作用 / NMRスクリーニング / インシリコスクリーニング / LIMキナーゼ / 細胞骨格制御 / 細胞間接着装置 / アクチン / 細胞骨格 / タンパク質間相互作用阻害剤 / 中分子創薬 |
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| Outline of Final Research Achievements |
Cell shapes and inter-cellular junctions are dynamically regulated by many scytosolic scafold proteins. Among them, we focused on the several PDZ-domain domains. We succeeded in obtaining new small chemical compounds that specifically inhibit the PDZ domains, including ZO-1-PDZ1, LNX1-PDZ2, and DVL-PDZ. These compounds are useful for chemical biology and phrmacological studies of epithelial cell homeostasis. In particular, our ZO-1-PDZ1 inhibitors are potent absorption enhancers that may improve effiacy of many existing drugs. LNX1-PDZ-inhibitors are thought to be useful for skin or intestinal barrier enhancers. DVL-PDZ inhibitors are candidates for developping anti-cancer drugs against triple negatice breast cancer.
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