Development of novel molecular-targeted medicine against aminopeptidase

新型抗氨肽酶分子靶向药物的开发

• 批准号: 21390373
• 负责人: KARAKO Takashi
• 金额: $ 11.15万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390373/
• 关键词: 分子標的治療薬; 肝細胞癌; 浸潤; APN; 血管新生

This study was aimed to develop novel inhibitors of aminopeptidase N(APN) overexpressed on cancer cell membrane and to evaluate the suppressive effect on cancer cell growth and angiogenesis. A newly-synthesized compound 24F, one of hydroxamic acid derivatives, inhibited the activity of aminopeptidases expressed on HL60 cell membrane. This compound inhibited the growth and invasion of hepatoma cell lines. In addition, incubation of vascular endothelial cells with 24F was found to be effective for the suppression of the angiogenic phenomena such as migration and tube formation. Furthermore, a newly-synthesized bestatin derivative LYP also had the ability to inhibit cancer cell growth as well as migration and tube formation of vascular endothelial cells. These results suggest that newly-synthesized aminopeptidase inhibitors are effective as an anti-cancer agent for hepatoma via inhibition of cancer cell invasion and angiogenesis surrounding cancer tissue.

本研究的目的是开发新型的癌细胞膜上过表达的氨肽酶N（APN）抑制剂，并评估其对癌细胞生长和血管生成的抑制作用。新合成的异羟肟酸衍生物24 F对HL 60细胞膜上表达的氨基肽酶活性有抑制作用。该化合物可抑制肝癌细胞株的生长和侵袭。此外，发现血管内皮细胞与24F的孵育对于抑制血管生成现象如迁移和管形成是有效的。此外，新合成的bestatin衍生物LYP也具有抑制癌细胞生长以及血管内皮细胞迁移和管形成的能力。这些结果表明，新合成的氨肽酶抑制剂通过抑制癌细胞侵袭和癌组织周围的血管生成而作为肝癌的抗癌剂是有效的。

项目成果

LY52, a caffeoyl pyrrolidine derivative, suppress invasion of both HepG2 and HepG2.2.15 cells via blocking MMP-2 activity

LY52 是一种咖啡酰吡咯烷衍生物，通过阻断 MMP-2 活性来抑制 HepG2 和 HepG2.2.15 细胞的侵袭

• 发表时间: 2009
• 作者: Xu HL;Zhao X;Inagaki Y;Kokudo N;et al.
• 通讯作者: et al.

Biochemical effects of des-gamma-carboxy prothrombin on the progression of henatocellular carcinoma.

脱γ-羧基凝血酶原对肝细胞癌进展的生化作用。

• 发表时间: 2010
• 作者: Inagaki Y;Qu XJ;Xu HL;Tang W;et al.
• 通讯作者: et al.

肝胆膵領域の癌におけるKL-6ムチンの臨床病理学的有用性

KL-6 粘蛋白在肝胆癌和胰腺癌中的临床病理学用途

• 发表时间: 2011
• 作者: Nakano K;Kumagai M;Shimoda S;Wakabayashi R;Nishiyama N;Kataoka K;稲垣善則
• 通讯作者: 稲垣善則

Evaluation of KL-6 mucin, atype of MUC1 mucin, as a potentialtarget for diagnosis and therapy ofintrahepatic cholangiocarcinoma

MUC1粘蛋白的一种类型KL-6粘蛋白作为肝内胆管癌诊断和治疗潜在靶点的评价

• 发表时间: 2010
• 作者: Nagai Y;et al;Kimura N;Tang W
• 通讯作者: Tang W

Novel aminopeptidase N (APN/CD13) inhibitor 24F can suppress invasion of hepatocellular carcinoma cells as well as angiogenesis.

• 发表时间: 2010-04
• 期刊: Bioscience trends
• 影响因子: 5.5
• 作者: Y. Inagaki;Wei Tang;Li Zhang;Guanhua Du;Wenfang Xu;N. Kokudo