| Project/Area Number |
25281017
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INOBE Manabu 金沢大学, 薬学系, 准教授 (10312414)
WAKASUGI Mitsuo 金沢大学, 薬学系, 助教 (80345595)
KUNISHIMA Munetaka 金沢大学, 薬学系, 教授 (10214975)
GOTO Kyoko 金沢大学, 薬学系, 准教授 (50180245)
ODA Akifumi 金沢大学, 薬学系, 准教授 (50433511)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | ケミカルバイオロジー / 化合物ライブラリー / スクリーニング / ヌクレオチド除去修復 / 阻害剤 / 低分子化合物 |
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| Outline of Final Research Achievements |
We recently identified a small-molecule inhibitor (NERi) of nucleotide excision repair in human cells, which induces proteasomal degradation of one of core NER factors, ERCC1-XPF. In this study, we have tried to uncover the detailed mechanism underlying the loss of ERCC1-XPF heterodimer after NERi treatment. We have finally identified two cellular proteins possibly involved in the proteosomal degradation of ERCC1-XPF. We have also determined a structure-activity relationship of NERi by comparing the activity of more than 100 derivatives. On the other hand, we could find no further compounds showing comparably high NER-inhibition activity with NERi after screening of another public chemical library.
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