| Project/Area Number |
26460149
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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 |
Drug development chemistry
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
Endo Satoshi 岐阜薬科大学, 薬学部, 助教 (60433207)
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| Co-Investigator(Renkei-kenkyūsha) |
TOYOOKA Naoki 富山大学, 大学院理工学研究部(工学), 教授 (10217565)
GODA Hiroaki 昭和大学, 薬学部, 教授 (60276160)
TANAKA Nobutada 昭和大学, 薬学部, 准教授 (00286866)
KUWATA Kazuo 岐阜大学, 大学院連合創薬医療情報研究科, 教授 (00170142)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アルドケト還元酵素 / 抗癌剤 / SNP / AKR1B10 / 構造活性相関 / 分子モデリング / 抗癌剤耐性克服 / SNPs / 構造安定性低下 / 阻害選択性の向上 |
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| Outline of Final Research Achievements |
In this study, we searched for novel inhibitors of Nrf2-inducible aldo-keto reductase (AKR), which is the core of oxidative stress defense mechanisms, and succeeded in development of the potent and selective AKR1B10 inhibitors at the present time. Since the AKR1B10 inhibitors exhibit both inhibitory effects on proliferation in lung cancer cells and overcoming resistance to chemotherapy in anticancer drug-resistant cells, they are expected to become adjuvant anticancer drugs enabling to overcome tolerance. Furthermore, we found inactive mutants of AKR which protects nerve cells against oxidative stress and elucidated the mechanism of the inactivation.
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