2023 Fiscal Year Final Research Report
Development of a novel TKI derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy
| Project/Area Number |
21K07215
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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 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Endo Yoshio 金沢大学, がん進展制御研究所, 准教授 (30211783)
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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)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 光線力学的治療 / 5-アミノレブリン酸 / チロシンキナーゼ阻害薬 |
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| Outline of Final Research Achievements |
Photodynamic diagnosis and therapy using 5-aminolevulinic acid (ALA) is a widely accepted non-invasive strategy against various cancers. Our prior research demonstrated that the Schiff base derivative, TX-816, markedly enhances the effect of ALA-based photodynamic therapy (PDT) by facilitating intracellular protoporphyrin IX (PpIX) accumulation. However, the instability of TX-816 in aqueous solutions leads to rapid hydrolysis into 3,5-dichlorosalicylaldehyde and 2-chloro-4-nitroaniline (CNA). In this study, we found that a TX-816 derivative (YS3-35), substituting CNA was substituted with dasatinib, notably enhances the effect on ALA-PDT. Furthermore, we synthesized a novel derivative, YS6-107, replacing CNA of TX-816 with gefitinib. YS6-107 also exhibited superior ALA-PDT-enhancing activity compared to gefitinib. These results suggest that Schiff base derivatives combined with tyrosine kinase inhibitors are effective lead compounds for developing novel ALA-PDT photosensitizers.
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| Free Research Field |
基礎腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、PpIXの排出ポンプとして働くトランスポーターであるABCG2を阻害するチロシンキナーゼ阻害剤にDCSAを導入したシッフ塩基は多機能型の光線力学的治療の効果増強剤の開発の有用なリード化合物となることが確認され、これまで有効性が確認されていなかった癌腫に対しても5-アミノレブリン酸による光線力学的治療の応用が期待される。国内外でもALA-PDT効果増強に関する報告は限られており、新規シッフ塩基化合物を用いたALA-PDT効果増強剤の開発研究は意義ある研究成果と考える。
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