Development of new BNCT sensitizer based on molecular chirality recognition of amino acid transporter LAT

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19348
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Chiba University
• Principal Investigator: ANZAI Naohiko 千葉大学, 大学院医学研究院, 教授 (70276054)
• Co-Investigator(Kenkyū-buntansha): 根本 哲宏 千葉大学, 大学院薬学研究院, 教授 (80361450) ; 松川 岳久 順天堂大学, 医学部, 准教授 (60453586)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: トランスポーター / 分子キラリティ / 分子標的創薬

Outline of Final Research Achievements

This study was based on the idea that chirality recognition of the two enantiomers of boronated phenylalanine could lead to selective toxicity effective against malignant tumors, and aimed to develop a new BNCT sensitizer that targets the transporter. Regarding the in vitro uptake evaluation of asymmetric compounds in human LAT1-expressing tumor-derived cells, we established an intracellular boron measurement system using LAICP-MS and succeeded in identifying trace amounts of boron taken up into the cells. Regarding the increase in selectivity between tumor-type LAT1 and normal-type LAT2, we confirmed the inhibitory effects of the existing LAT1 inhibitor JPH203 and the LAT2 inhibitor KYT0284 in a stable expression experimental system, and reaffirmed the need for continued investigation.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

陽子線、重粒子線などの一般放射線治療では出来ないがん細胞と正常細胞の区別が可能な「正常細胞に非常に優しいがん治療法」であるBNCTは我が国において病院設置型小型加速器が開発されたことにより世界で最初に国内医療機関での普及が大きく見込まれている。この適応拡大のためには腫瘍選択性が高いより有効な新規ホウ素化合物合成は不可欠であり、本研究が今後の創薬開発のための重要な基盤情報となるものと思われる。