The innovative drug development that targeted molecules associated with coronary artery diseases and its functional analysis
Project/Area Number |
16H04726
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Medical genome science
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Research Institution | National Center for Geriatrics and Gerontology |
Principal Investigator |
OZAKI Kouichi 国立研究開発法人国立長寿医療研究センター, メディカルゲノムセンター, 部長 (50373288)
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Co-Investigator(Kenkyū-buntansha) |
伊藤 薫 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50375664)
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Research Collaborator |
YOSHII Mayumi
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
|
Keywords | 虚血性心疾患 / 動脈硬化 / 創薬 / 虚血性心疾患感受性分子 / 低分子化合物 / 虚血性心疾患感受性分子群 / 分子機能 / 結合阻害低分子化合物 / BRAP / NFKBIB / 結合抑制低分子 / FURIN / LDLR / ELISA系 / 感受性分子 |
Outline of Final Research Achievements |
We have performed the discovery of low-molecular weight compound (LMWC) which interfere the interaction and function of BRAP, associated most strongly with coronary artery diseases (CAD) susceptibility in Japanese, and IkB-beta a mediator of inflammation. We developed ELISA system for BRAP-IkB-beta interaction and performed interfere experiments for the binding by 9,600 low molecular weight compounds as well as selected its structural analogs. Finally, we have obtained 9 LMWCs that strongly interfered the BRAP-IkB-beta binding inwhich 3 molecules inhibited more than 40% of the proliferation of human artery smooth muscle cells. We also selected FURIN associated with CAD as another target for drug development. FURIN is a molecule with structural similarity of PCSK9, and interacts with LDL receptor. We have also developed ELISA system for FURIN-LDLR binding and have implemented LMWC screening that interfered the interaction using libraries consist of 9,600 and 22,400 molecules so far.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果は遺伝学、分子生物学的手法により発見したCADの真の感受性分子をターゲットとした創薬に関連しており、これまでに無い革新的かつ先端的な点が学術的意義として挙げられる。また、CADは日本を含む世界における死因が上位である疾患の一つであることからその新たな予防法、革新的な治療法に繋がる成果の開発は社会的意義がある。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Risk prediction models for dementia constructed by supervised principal component analysis using miRNA expression data2019
Author(s)
Shigemizu D, Akiyama S, Asanomi Y, Boroevich KA, Sharma A, Tsunoda T, Matsukuma K, Ichikawa M, Sudo H, Takizawa S, Sakurai T, Ozaki K, Ochiya T, Niida S.
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Journal Title
Communication Biology
Volume: 2
Issue: 1
Pages: 77-77
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure.2018
Author(s)
Nomura S, Satoh M, Fujita T, Higo T, Sumida T, Ko T, Yamaguchi T, Tobita T, Naito AT, Ito M, Fujita K, Harada M, Toko H, Kobayashi Y, Ito K, Takimoto E, Akazawa H, Morita H, Aburatani H, Komuro I.
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Journal Title
Nat Commun.
Volume: 9
Issue: 1
Pages: 4435-4435
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort.2018
Author(s)
1)Nagata Y, Hirayama A, Ikeda S, Shirahata A, Shoji F, Maruyama M, Kayano M, Bundo M, Hattori K, Yoshida S, Goto Y, Urakami K, Soga T, Ozaki K and Niida S.
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Journal Title
Biomarker Research
Volume: 6
Issue: 1
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of six novel genetic loci associated with atrial fibrillation in Japanese population.2017
Author(s)
Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT, AFGen Consortium, Ogishima S, Yamamoto M, Satoh M, Sasaki M, Yamaji T, Iwasaki M, Tsugane S, Tanaka K, Naito M, Wakai K, Tanaka H, Furukawa T, Kubo M, Ito K, Kamatani Y, Tanaka T.
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Journal Title
Nature Genetics
Volume: -
Issue: 6
Pages: 953-958
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A functional SNP in FLT1 increases risk of coronary artery disease in a Japanese population.2016
Author(s)
Konta A, Ozaki K, Sakata Y, Takahashi A, Morizono T, Suna S, Onouchi Y, Tsunoda T, Kubo M, Komuro I, Eishi Y, Tanaka T.
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Journal Title
Journal of Human Genetics
Volume: 61
Issue: 5
Pages: 435-441
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Trans-ethnic meta-analysis of genome-wide association studies for coronary artery disease reveals genetic differences between Japanese and Europeans2018
Author(s)
Matsunaga H, Koyama K, Onouchi Y, Ozaki K, Morita H, Akazawa H, Komuro I, Akiyama M, Kubo M, Kamatani Y, Ito K.
Organizer
ASHG 2018 Annual Meeting (USA)
Related Report
Int'l Joint Research
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[Presentation] Trans-Ethnic Meta-Analysis of Genome-Wide Association Studies for Coronary Artery Disease Highlights the Importance of Immune System2018
Author(s)
Matsunaga H, Ito K, Akiyama M, Koyama S, Onouchi Y, Ozaki K, Morita H, Akazawa H, Kamatani Y, Ko,uro I.
Organizer
American Heart Association SCIENTIFIC SESSION 2018 (USA)
Related Report
Int'l Joint Research
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[Presentation] 14.The construction of risk prediction models for dementia with supervised principal component analysis using miRNA expression data2018
Author(s)
Shigemizu D, Akiyama S, Asanomi Y, Boroevich KA, Sharma A, Tsunoda T, Matsukuma K, Ichikawa M, Sudo H, Takizawa S, Sakurai T, Ozaki K, Niida S.
Organizer
The American Society of Human Genetics 2018
Related Report
Int'l Joint Research
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