2018 Fiscal Year Final Research Report
Identification of novel candidate compounds for the treatment of lung squamous cell carcinoma by academic drug discovery
| Project/Area Number |
16K15638
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
猶本 良夫 川崎医科大学, 医学部, 教授 (00237190)
山辻 知樹 川崎医科大学, 医学部, 教授 (40379730)
高岡 宗徳 川崎医科大学, 医学部, 講師 (50548568)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Midkine / 分子標的治療法 / 肺扁平上皮癌 |
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| Outline of Final Research Achievements |
We have developed a specific inhibitor for cancer-specific growth factor Midkine: iMDK, and reported that the small compound can inhibit PI3Kinase / AKT pathway and induce an antitumor effect in lung cancer. In the present study, by optimizing the structure, we have synthesized derivatives of iMDK as the lead compound and investigated the antitumor properties of these small molecule compounds.
In HCC95 lung squamous cell carcinoma cells, two of the newly synthesized compounds showed antitumor activity at lower concentrations than iMDK. Furthermore, immunoblot revealed that these two compounds suppressed the phosphorylation of AKT at low concentration and induced apoptosis.
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| Free Research Field |
非小細胞肺癌、胸膜中皮腫に対する新規補助療法の開発
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| Academic Significance and Societal Importance of the Research Achievements |
肺扁平上皮癌における有効な分子標的療法は未だ樹立されていない。その中で近年、肺扁平上皮癌の増殖・進展におけるPI3Kinaseの関与が報告され、また米国癌ゲノムアトラス研究ネットワーク（The Cancer Genome Atlas Research Network）から肺扁平上皮癌の多くにPIK3CA変異が認められることが報告されている。検討に用いたHCC95株など、これらの腫瘍においてはしばしば、下流のAKTの活性化が見られる。派生化合物X,Yは当該肺癌細胞株に対し低濃度で抗腫瘍性を示し、臨床化合物として有望と考えられた。
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