Development of anti-cancer agents targeting the endocytic pathway

开发针对内吞途径的抗癌药物

• 批准号: 22681034
• 负责人: KAWATANI Makoto
• 金额: $ 14.98万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22681034/
• 关键词: 癌; 小分子化合物; エンドサイトーシス

The purpose of this study is to construct a cell morphology-based high-content screening system and to develop anti-cancer agents targeting the endocytic pathway. We constructed a chemical-genetic phenotype profiling system based on the high-content cell morphology database, Morphobase. We showed that NPD1801, which perturbs the endocytic pathway, targeted calmodulin, caused the activation of Ras-Raf pathway, the inhibition of the fusion of late endosome and lysosome, and the dysfunction of lysosome, and resulted in the cancer cell death.

本研究的目的是构建一个基于细胞形态的高含量筛选系统，并开发针对内吞途径的抗癌药物。我们构建了一个基于高含量细胞形态数据库Morphobase的化学遗传表型分析系统。我们发现，干扰内吞途径的NPD1801靶向钙调蛋白，导致Ras-Raf通路激活，抑制晚期内切体与溶酶体的融合，导致溶酶体功能障碍，导致癌细胞死亡。

项目成果

Effect of Reveromycin A on Experimental Tooth Movement in OPG-/- Mice

• DOI: 10.1177/0022034512451026
• 发表时间: 2012-08-01
• 期刊: JOURNAL OF DENTAL RESEARCH
• 影响因子: 7.6
• 作者: Tanaka, M.;Miyazawa, K.;Goto, S.
• 通讯作者: Goto, S.

Identification of a molecular target for RKB3564F070, a new cytotoxic fungal metabolite

鉴定 RKB3564F070（一种新的细胞毒性真菌代谢物）的分子靶标

• 发表时间: 2012
• 作者: 川谷誠;青野晴美;室井誠;二村友史;長田裕之
• 通讯作者: 長田裕之

Discovery of a Small Molecule PDI Inhibitor That Inhibits Reduction of HIV-1 Envelope Glycoprotein gp120

• DOI: 10.1021/cb100387r
• 发表时间: 2011-03-01
• 期刊: ACS CHEMICAL BIOLOGY
• 影响因子: 4
• 作者: Khan, Maola M. G.;Simizu, Siro;Osada, Hiroyuki
• 通讯作者: Osada, Hiroyuki

Violaceols Function as Actin Inhibitors Inducing Cell Shape Elongation in Fibroblast Cells

• DOI: 10.1271/bbb.120074
• 发表时间: 2012-08-01
• 期刊: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
• 影响因子: 1.6
• 作者: Asami, Yukihiro;Jang, Jae-Hyuk;Ahn, Jong Seog
• 通讯作者: Ahn, Jong Seog

Glyoxalase-I is a novel target against Bcr-Abl^+ leukemic cells acquiring stem-like characteristics in hypoxic environment.

乙二醛酶-I是针对在缺氧环境中获得干细胞样特征的Bcr-Abl^白血病细胞的新靶点。

• 期刊: Cell Death Diff. (In press)
• 作者: M.Takeuchi;S.Kimura;J.Kuroda;E.Ashihara;M.Kawatani;H.Osada;K.Umezawa;E.Yasui;M.Imoto;T.Tsuruo;A.Yokota;R.Tanaka;R.Nagao;T.Nakahata;Y. Fujiyama;T.Maekawa
• 通讯作者: T.Maekawa