| Project/Area Number |
23300365
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Clinical oncology
|
|---|
| 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, 医学教育部医学科専門課程, 教授 (40505260)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANUMA Sei-ichi 東京理科大学, 薬学部・生化学, 教授 (10142449)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2011-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2011: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
|---|
| 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 |
|---|
| 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.
|
