2013 Fiscal Year Final Research Report
Development and biological evaluation of small molecule inhibitors for Met using a new strategy
| Project/Area Number |
23300365
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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 |
Clinical oncology
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| Research Institution | National Defense Medical College |
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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, 医学教育部医学科専門課程, 教授 (40505260)
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| Co-Investigator(Kenkyū-buntansha) |
TANUMA Sei-ichi 東京理科大学, 薬学部・生化学, 教授 (10142449)
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| Co-Investigator(Renkei-kenkyūsha) |
MORIMOTO Yuji 防衛医科大学校, 医学教育部専門課程, 准教授 (10449069)
MATSUO Hirotaka 防衛医科大学校, 医学教育部専門課程, 講師 (00528292)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | Met / 分子標的薬 / Imatinib / COSMOS法 / リード化合物 / ホモロジーモデリング / Hot spot / Kinase活性 |
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| Research Abstract |
Met tyrosine kinase transduces multifunctional signals that enhance tumor progression, invasion, and angiogenesis. Also Met correlates well with poor prognosis in clinical cancers. Therefore, Met is considered to be a suitable molecule for targeting therapy. Introducing our new strategy named COSMOS (Conversion to Small Molecules through Optimized-Peptides Strategy), we have designed candidate molecules for Met inhibitors. Main strategic concept of the drug design for Met was based on its similarity to the tertiary structure of T315I-mutated type Bcr-Abl. Among various molecules tested, two compounds inhibited Met kinase activity most effectively, thereby showing the possibility of becoming candidate lead compounds. We also developed oligopeptides that can bind Met kinase and effectively inhibits its activity. These results provide information about a new strategy for developing small molecule inhibitors for Met.
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Research Products
(13 results)
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[Journal Article] Overexpression of HGF Promotes HBV-Induced Hepatocellular Carcinoma Progression and Is an Effective Indicator for Met-Targeting Therapy2013
Author(s)
Xie Q., Su Y., Dykema K., Johnson J., Koeman J., De Giorgi V., Huang A., Schlegel R., Essenburg C., Kang L., Iwaya K., Seki S., Khoo S.K., Zhang B., Buonaguro F., Marincola F. M., Furge K., Vande Woude G.F., and Shinomiya N
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Journal Title
Genes Cancer
Volume: 4
Pages: 247-260
DOI
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[Journal Article] A new protocol to discover novel anti-aging compounds2012
Author(s)
Uchiumi F., Oyama T., Ozaki K., Fukui M., Ogawa H., Sasaki Y., Tachibana H., Fukushima C., Fujikawa M., Abe H., Larsen S., and Tanuma S
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Journal Title
Pharmaceutica Analytica Acta
Volume: 3(7)
Pages: 166
DOI
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[Journal Article] Cancer susceptibility polymorphism of p53 at codon 72 affects phosphorylation and degradation of p53 protein2011
Author(s)
Ozeki C., Sawai Y., Shibata T., Kohno T., Okamoto K., Yokota J., Tashiro F., Tanuma S., Sakai R., Kawase T., Kitabayashi I., Taya Y., and Ohki R
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Journal Title
J Biol Chem
Volume: 286(20)
Pages: 18251-60
DOI
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[Remarks] 研究代表者の所属研究機関である防衛医科大学校と調整を続けてきたが, 防衛省の情報保証に関する規則上, 現状では直ちに防衛医科大学校の公的な web 上で公開することは困難である. したがって, 規則に抵触しない形で研究成果に関する独自の web ページの作成を検討中である.
