2022 Fiscal Year Final Research Report
Development of a selective inhibitor against Na+/H+ exchange transporter 5 (NHE5), which is a target candidate molecule for gastrointestinal cancer.
| Project/Area Number |
20K09030
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宇都 義浩 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 教授 (20304553)
遠藤 良夫 金沢大学, がん進展制御研究所, 准教授 (30211783)
滝野 隆久 金沢大学, GS教育系, 教授 (40322119)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Na+/H+交換輸送体5 / アミロライド / UTX-143 / 殺細胞活性 / 浸潤抑制効果 / 遊走抑制効果 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop a selective inhibitor against Na+/H+ exchange transporter 5 (NHE5), which is a target candidate molecule for gastrointestinal cancer. We attempted to develop a novel NHE5 selective inhibitor with 18 derivatives were designed and synthesized by introducing various functional groups to the phenyl group of amiloride derivative UTX-138 using the method of structure-activity relationship. Regarding NHE1 and NHE5 inhibitory activity, UTX-143 showed the highest NHE5 inhibitory activity and NHE5 selectivit. Next, UTX-143 showed cytotoxic activity, cell invasion inhibitory effect, and migration inhibitory effect against HT-1080 human fibrosarcoma cells. On the other hand, the antiproliferative effect of UTX-143 on normal human skin fibroblasts was very weak. Based on the above results, we succeeded in develop a novel NHE5-selective inhibitor UTX-143 that has tumor-specific antiproliferative, invasion-inhibiting, and migration-inhibiting effects.
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| Free Research Field |
消化器癌
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果の学術的意義としては、Na+/H+交換輸送体5が消化器癌の標的分子であることを見出した事、NHE非選択的阻害剤アミロライドをリード化合物としてNHE5選択的阻害剤UTX-143を創出できた事が挙げられる。また、社会的意義としては、新しい抗がん剤候補物質の創出による消化器癌治療の奏効率向上の可能性が考えられる。
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