Development of novel lead compounds with enhancing effect on ALA-based photodynamic therapy

开发增强基于 ALA 的光动力疗法效果的新型先导化合物

• 批准号: 23501305
• 负责人: ENDO YOSHIO
• 金额: $ 3万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23501305/
• 关键词: 光線力学的療法; PDT; 5-アミノレブリン酸; 5-ALA; トランスポーター; 効果増強剤; 光線力学療法; ALA; PEPT1; ABCG2; 増強剤; 耐性細胞

Protoporphyrin IX (PpIX)-dependent photodynamic diagnosis (PDD) and therapy (PDT) using 5-aminolevulinic acid (ALA-PDD and ALA-PDT) are widely recognized novel therapeutic strategies for the treatment of various cancers.Previously, we demonstrated that the balance between the influx of ALA through the transporter PEPT1 and the efflux of intracellular PpIX through the ABC transporter ABCG2 determines the sensitivity of cancer cells to ALA-PDT. Recently, we found that the Schiff base derivative TX-816 could significantly increase the effect of ALA-PDT. The ability of TX-816 to enhance the efficacy of ALA-PDT was markedly stronger than that of dipyridamole, which inhibits ABCG2 and equilibrative nucleoside transporters. Furthermore, TX-816 could recover the sensitivity to ALA-PDT in cancer cells with acquired resistance. These results indicate TX-816 is a potent lead compound to develop an ALA-PDT sensitizer.

使用5-氨基乙酰丙酸的原卟啉IX（PpIX）依赖性光动力学诊断（PDD）和治疗（PDT）ALA-PDD和ALA-PDT是广泛认可的用于治疗各种癌症的新型治疗策略。我们证明了ALA通过转运蛋白PEPT 1的流入和胞内PpIX通过ABC转运蛋白ABCG 2的流出之间的平衡决定了癌细胞对ALA的敏感性。PDT。最近，我们发现席夫碱衍生物TX-816可以显著增强ALA-PDT的效应。TX-816增强ALA-PDT疗效的能力明显强于抑制ABCG 2和平衡核苷转运蛋白的双嘧达莫。此外，TX-816可以恢复具有获得性耐药的癌细胞对ALA-PDT的敏感性。这些结果表明TX-816是开发ALA-PDT敏化剂的有效先导化合物。

项目成果

Significance of membrane transporters in determining the ALA-PDT sensitivity in human cancer cells.

膜转运蛋白在确定人类癌细胞 ALA-PDT 敏感性中的意义。

• 发表时间: 2011
• 作者: Yoshio Endo;Shun-ichiro Ogura;Yuichiro Hagiya;Yutaka Yonemura;Masahiro Ishizuka;Tohru Tanaka;Katsushi inoue;Kiwamu Takahashi;Motowo Nakajima;Masashi Kimura
• 通讯作者: Masashi Kimura

腫瘍移植鶏卵モデルを用いた5-aminolevulinic acid およびTin chlorin e6 の超音波増感活性の評価

利用肿瘤植入鸡蛋模型评价5-氨基乙酰丙酸和二氢锡e6的超声增敏活性

• 发表时间: 2014
• 作者: 玉谷 大;宇都義浩;水木佑輔;國安翔太;野口智帆;遠藤良夫;中西郁夫;大久保敬;石塚昌宏;田中 徹;口池大輔;久保健太郎;乾 利夫;堀 均
• 通讯作者: 堀 均

Pivotal Role of PEPT1 and ABCG2 on 5-Aminolevulinic Acid (ALA)-based Photodynamic Sensitization of Gastric Cancer Cells in Vitro

PEPT1 和 ABCG2 对基于 5-氨基乙酰丙酸 (ALA) 的体外胃癌细胞光动力敏化的关键作用

• 发表时间: 2011
• 作者: Yuichiro Hagiya;Yoshio Endo;Yutaka Yonemura;Kiwamu Takahashi;Masahiro Ishizuka;Fuminori Abe;Motowo Nakajima;Toshihisa Ishikawa;Shun-ichiro Ogura
• 通讯作者: Shun-ichiro Ogura

Development of antimetastatic hypoxic cytotoxin TX-2137 targeting for Akt/protein kinase B

开发针对 Akt/蛋白激酶 B 的抗转移缺氧细胞毒素 TX-2137

• 发表时间: 2013
• 作者: Yoshihiro Uto;Yoshio Endo;Hiroshi Sato;Hitoshi Hori
• 通讯作者: Hitoshi Hori

Tumor Suppressor Protein p53-dependent Cell Death Induced by 5-Aminolevulinic Acid (ALA)-based Photodynamic Sensitization of Cancer cells in Vitro.

基于 5-氨基乙酰丙酸 (ALA) 的体外癌细胞光动力敏化诱导肿瘤抑制蛋白 p53 依赖性细胞死亡。

• 发表时间: 2012
• 期刊: ALA-Porphyrin Science (ISSN 2187-1639)
• 作者: Hagiya Y;Endo Y (equal contribution);Yonemura Y;Okura I;Ogura S
• 通讯作者: Ogura S