2022 Fiscal Year Final Research Report
Development of novel boron carrier utilizing amino acid transporters specific for glutamine addiction of cancer cells
| Project/Area Number |
19H03352
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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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| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平山 祐 岐阜薬科大学, 薬学部, 准教授 (10600207)
辻 美恵子 岐阜薬科大学, 薬学部, 助教 (40709721)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | グルタミン中毒 / ホウ素中性子捕捉療法 / L型アミノ酸トランスポーター / がん治療 |
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| Outline of Final Research Achievements |
We aimed to develop a boron carrier for BNCT that selectively and efficiently accumulates 10B atoms in tumor cells. Therefore, focusing on "glutamine addiction" caused by metabolic reprogramming of tumors, we designed and synthesized a novel carborane-containing amino acid derivatives targeting L-type amino acid transporter 1 (LAT1), which is strongly expressed in malignant tumor cells. Among the new compounds, BC2 gave the highest intracellular boron uptake. This was dose-dependent, with 10-fold higher uptake than the known LAT1-dependent boron carrier, L- BPA, at the same dose (10 μgB/mL). BC-2 showed the highest enhancement of the cell killing effect of thermal neutrons on T98G cells.
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| Free Research Field |
創薬化学、ケミカルバイオロジー
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| Academic Significance and Societal Importance of the Research Achievements |
近年、小型加速器が実用化され、ホウ素中性子捕捉療法に注目が集まっている。本研究では、現在臨床適用されるL-BPAを大きく上回る腫瘍取り込みとホウ素中性子捕捉効果を示す有望な新規ホウ素キャリアを開発した。本化合物は、簡便に合成でき、難治性腫瘍に強発現しているLAT-1を介して取り込まれることを明らかにした。本化合物の臨床適用が実現すれば、がん選択的治療法として有望なホウ素中性子捕捉療法の実用化を加速し、転移性がん、難治性がん治療に貢献するものと期待される。
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