Development of new small molecules for Met stimulator and building up foundations of medical application
Project/Area Number |
18H02685
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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 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | National Defense Medical College |
Principal Investigator |
Shinomiya Nariyoshi 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 分子生体制御学, 教授 (40505260)
|
Co-Investigator(Kenkyū-buntansha) |
田沼 靖一 東京理科大学, 研究推進機構総合研究院, 教授 (10142449)
中村 浩之 東京工業大学, 科学技術創成研究院, 教授 (30274434)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
Keywords | c-Met / 受容体型チロシンキナーゼ / 分子創薬 / 阻害剤 / 刺激剤 / COSMOS法 / c-Met / In silico創薬 / Kinase阻害剤 / Met stimulator / 低分子阻害薬 / Met stimulator / 低分子医薬 / 抑制剤 / c-Met / in silico創薬 / キナーゼ阻害剤 / Stimulator |
Outline of Final Research Achievements |
Met is a membrane receptor tyrosine kinase involved in liver regeneration and tissue repair. Based on the structures of the candidate low molecular weight compounds of Met stimulator obtained so far, we designed and synthesized new compounds with lower toxicity, and confirmed their Met stimulating activity on cells. In addition, through the investigation of the relationship between the molecular structure and Met stimulating activity, it was confirmed that the dimethyl-amino group in the side chain is important for the expression of activity. Currently, we are trying to further improve the structure from the viewpoint of in silico drug designing for practical use.
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Academic Significance and Societal Importance of the Research Achievements |
本研究において、in silico創薬(コンピュータを用いた薬剤デザイン)に構造-活性解析の観点を加えることにより、薬剤活性と結合部位の関係が徐々に明らかになってきている。合成された低分子Met Stimulatorが、標的分子であるMetを活性化し生物学的機能を十分に発揮することが証明できれば、本研究が今後の新薬開発に向けての重要なステップを示したことになる。
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Report
(4 results)
Research Products
(113 results)
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[Journal Article] A common variant of LDL receptor related protein 2 (LRP2) gene is associated with gout susceptibility: a meta-analysis in a Japanese population.2020
Author(s)
Akashi A, Nakayama A, Kamatani Y, Higashino T, Shimizu S, Kawamura Y, Imoto M, Naito M, Hishida A, Kawaguchi M, Takao M, Matsuo M, Takada T, Ichida K, Ooyama H, Shinomiya N, Matsuo H.
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Journal Title
Hum Cell.
Volume: 33
Issue: 2
Pages: 303307-303307
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[Journal Article] Dysfunctional missense variant of OAT10/SLC22A13 decreases gout risk and serum uric acid levels.2020
Author(s)
Higashino T, Morimoto K, Nakaoka H, Toyoda Y, Kawamura Y, Shimizu S, Nakamura T, Hosomichi K, Nakayama A, Ooyama K, Ooyama H, Shimizu T, Ueno M, Ito T, Tamura T, Naito M, Nakashima H, Kawaguchi M, Takao M, Kawai Y, Osada N, Ichida K, Yamamoto K, Suzuki H, Shinomiya N, Inoue I, Takada T, Matsuo H.
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Ann Rheum Dis.
Volume: 79(1)
Issue: 1
Pages: 164-166
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[Journal Article] Identification of GLUT12/SLC2A12 as a urate transporter that regulates the blood urate level in hyperuricemia model mice.2020
Author(s)
Toyoda Y, Takada T, Miyata H, Matsuo H, Kassai H, Nakao K, Nakatochi M, Kawamura Y, Shimizu S, Shinomiya N, Ichida K, Hosoyamada M, Aiba A, Suzuki H
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Proc. Natl.Acad. Sci. USA
Volume: 117
Issue: 31
Pages: 18175-18177
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[Journal Article] A potential mechanism of tumor progression during systemic infections via the hepatocyte growth factor (HGF)/c-Met signaling pathway.2020
Author(s)
Tsujimoto H, Horiguchi H, Matsumoto Y, Takahata R, Shinomiya N, Yamori T, Miyazaki H, Ono S, Saitoh D, Kishi Y, Ueno H.
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Journal Title
J Clin. Med
Volume: 9
Issue: 7
Pages: 2074-2074
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[Journal Article] Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity2020
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S. Fuse, K. Suzuki, T. Kuchimaru, T. Kadonosono, H. Ueda, S. Sato, S. Kizaka-Kondoh, H. Nakamura
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Bioorg Med. Chem
Volume: 28(1)
Issue: 1
Pages: 115207-115207
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[Journal Article] High Expression of c-Met, PKCλ and ALDH1A3 Predicts a Poor Prognosis in Late-stage Breast Cancer.2020
Author(s)
Motomura H, Nozaki Y, Onaga C, Ozaki A, Tamori S, Shiina TA, Kanai S, Ohira C, Hara Y, Harada Y, Takasawa R, Hanawa T, Tanuma SI, Mano Y, Sato T, Sato K, Akimoto K
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Journal Title
Anticancer Res.
Volume: 40
Issue: 1
Pages: 35-52
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[Journal Article] Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals.2019
Author(s)
Nakatochi M, Kanai M, Nakayama A, Hishida A, Kawamura Y, Ichihara S, Akiyama M, Ikezaki H, Furusyo N, Shimizu S, Yamamoto K, et al.
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Journal Title
Commun Biol.
Volume: 2
Issue: 1
Pages: 115-115
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NAID
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[Journal Article] Effect of piceatannol-rich passion fruit seed extract on human glyoxalase I-mediated cancer cell growth.2019
Author(s)
Yamamoto T, Sato A, Takai Y, Yoshimori A, Umehara M, Ogino Y, Inada M, Shimada N, Nishida A, Ichida R, Takasawa R, Maruki-Uchida H, Mori S, Sai M, Morita M, Tanuma SI
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Journal Title
Biochem Biophys Rep.
Volume: 20
Pages: 100684-100684
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[Journal Article] Characterization of the Human E2F4 Promoter Region and Its Response to 12-O-tetradecanoylphorbol-13-acetate.2019
Author(s)
Hamada H, Goto Y, Arakawa J, Murayama E, Ogawa Y, Konno M, Oyama T, Asai M, Sato A, Tanuma SI, Uchiumi F
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Journal Title
J Biochem
Volume: 166
Issue: 4
Pages: 363-373
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NAID
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[Journal Article] Anticancer effects of a non-narcotic opium alkaloid medicine, papaverine, in human glioblastoma cells,2019
Author(s)
Inada M, Shindo M, Kobayashi K, Sato A, Yamamoto Y, Akasaki Y, Ichimura K, Tanuma SI,
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Journal Title
PLoS One,
Volume: 14(5)
Issue: 5
Pages: e0216358-e0216358
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[Journal Article] Characterization of a novel microRNA, miR-188, elevated in serum of muscular dystrophy dog model.2019
Author(s)
Shibasaki H, Imamura M, Arima S, Tanihata J, Kuraoka M, Matsuzaka Y, Uchiumi F, Tanuma SI, Takeda S.
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Journal Title
PLoS One
Volume: 14(1)
Issue: 1
Pages: e0211597-e0211597
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[Journal Article] Papaverine identified as an inhibitor of high mobility group box 1/receptor for advanced glycation end-products interaction suppresses high mobility group box 1-mediated inflammatory responses.2019
Author(s)
Tamada K, Nakajima S, Ogawa N, Inada M, Shibasaki H, Sato A, Takasawa R, Yoshimori A, Suzuki Y, Watanabe N, Oyama T, Abe H, Inoue S, Abe T, Yokomizo T, Tanuma S.
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Journal Title
Biochem Biophys Res Commun
Volume: 511
Issue: 3
Pages: 665-670
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[Journal Article] A common variant of MAF/c-MAF, transcriptional factor gene in the kidney, is associated with gout susceptibility.2018
Author(s)
Higashino T, Matsuo H, Okada Y, Nakashima H, Shimizu S, Sakiyama M, Tadokoro S, Nakayama A, Kawaguchi M, Komatsu M, Hishida A, Nakatochi M, Ooyama H, Imaki J, Shinomiya N.
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Journal Title
Human Cell
Volume: 31
Issue: 1
Pages: 10-13
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[Journal Article] Common variant of BCAS3 is associated with gout risk in Japanese population: the first replication study after gout GWAS in Han Chinese.2018
Author(s)
Sakiyama M, Matsuo H, Nakaoka H, Kawamura Y, Kawaguchi M, Higashino T, Nakayama A, Akashi A, Ueyama J, Kondo T, Wakai K, Sakurai Y, Yamamoto K, Ooyama H, Shinomiya N.
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Journal Title
BMC Med Genet.
Volume: 19
Issue: 1
Pages: 96-96
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[Journal Article] Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.2018
Author(s)
Takada T, Yamamoto T, Matsuo H, Tan JK, Ooyama K, Sakiyama M, Miyata H, Yamanashi Y, Toyoda Y, Higashino T, Nakayama A, Nakashima A, Shinomiya N, Ichida K, Ooyama H, Fujimori S, Suzuki H
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
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[Journal Article] Glyoxalase 1 gene is highly expressed in basal-like human breast cancers and contributes to survival of ALDH1-positive breast cancer stem cells2018
Author(s)
Shoma Tamori, Yuka Nozaki, Hitomi Motomura, Hiromi Nakane, Reika Katayama, Chotaro Onaga, Eriko Kikuchi, Nami Shimada, Yuhei Suzuki, Mei Noike, Yasushi Hara, Keiko Sato, Tsugumichi Sato, Kouji Yamamoto, Takehisa Hanawa, Misa Imai, Ryo Abe, Atsushi Yoshimori, Ryoko Takasawa, Sei-Ichi Tanuma and Kazunori Akimoto
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Journal Title
Oncotarget
Volume: 9
Issue: 92
Pages: 36515-36529
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[Presentation] Development of a gene expression database of pancreatic ductal adenocarcinoma cases by NGS-combined HiCEP to identify tumor markers2020
Author(s)
Takao M, Araki R, Shimizu S, Kawaguchi M, Akiyoshi Nakayama, Kitamura Y, Kawamura Y, Maehara K, Abe M, Ito K, Hoshikawa M, Yamamoto J, Kishi Y, Shinomiya N,
Organizer
American Association for Cancer Research (AACR) 2020.
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[Presentation] Identification of candidate tumor marker genes for pancreatic ductal adenocarcinoma tissue by NGS-HiCEP method2020
Author(s)
Takao M, Matsuo H, Shimizu S, Kitamura Y, Kawaguchi M, Nakayama A, Kawamura Y, Ito K, Kishi Y, Shinomiya N
Organizer
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[Presentation] 次世代シークエンシングの併用によるHiCEP法(NGS-HiCEP法)の開発―腎癌組織の網羅的遺伝子発現データベースの構築と腎癌マーカーの同定2020
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[Presentation] HiCEP法と次世代シークエンシングを併用した膵癌マーカーの同定2020
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第65回防衛衛生学会. (東京)
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第30回日本疫学会学術総会. (京都)
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[Presentation] Development of the gene expression database of pancreatic ductal adenocarcinoma cases by NGS combined HiCEP method to identify the tumor markers.2019
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Author(s)
高尾幹也, 松尾洋孝, 荒木良子, 清水聖子, 川口真, 中山昌喜, 河村優輔, 青柳有香, 前原一輝, 湯野川春信, 安倍真澄, 伊藤敬一, 岸庸二, 四ノ宮成祥.
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第37回日本ヒト細胞学会学術集会. (三鷹)
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Author(s)
高尾幹也, 松尾洋孝, 清水聖子, 川口真, 中山昌喜, 河村優輔, 伊藤敬一, 星川真有美, 山本順司, 岸庸二, 四ノ宮成祥.
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第78回日本癌学会学術総会. (京都)
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Author(s)
川口真, 松尾洋孝, 荒木良子, 清水聖子, 高尾幹也, 中山昌喜, 北村陽典, 湯野川春信, 安倍真澄, 四ノ宮成祥, 伊藤敬一.
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第107回日本泌尿器科学会総会. (名古屋)
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[Book] Mitochondrial Diseases2018
Author(s)
Fumiaki Uchiumi, Jun Arakawa, Yutaka Takihara, Motohiro Akui, Hiroshi Hamada, Sei-ichi Tanuma
Total Pages
496
Publisher
IntechOPEN Limited (London)
ISBN
9781789236750
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[Book] New Research on Cell Aging and Death2018
Author(s)
Yutaka Takihara, Daisuke Sudo, Jun Arakawa, Mayu Takahashi, Akira Sato, Sei-ichi Tanuma, Fumiaki Uchiumi
Total Pages
169
Publisher
Nova Science Publishers, Inc., Hauppauge, NY
ISBN
9781536136265
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