Discovery of novel tetracyclic compounds as anaplastic lymphoma kinase inhibitors

被引：32
作者：
Kinoshita, Kazutomo [1 ]
Ono, Yoshiyuki [2 ]
Emura, Takashi [2 ]
Asoh, Kohsuke [1 ]
Furuichi, Noriyuki [1 ]
Ito, Toshiya [1 ]
Kawada, Hatsuo [1 ]
Tanaka, Shota [2 ]
Morikami, Kenji [2 ]
Tsukaguchi, Toshiyuki [1 ]
Sakamoto, Hiroshi [1 ]
Tsukuda, Takuo [1 ]
Oikawa, Nobuhiro [1 ]
机构：
[1] Chugai Pharmaceut Co Ltd, Kamakura Res Labs, Kanagawa 2478530, Japan
[2] Chugai Pharmaceut Co Ltd, Fuji Gotemba Res Labs, Shizuoka 4128513, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 12期
关键词：
Anaplastic lymphoma kinase; Kinase inhibitors; Antitumor efficacy; LUNG-CANCER; GENE; ALK; IDENTIFICATION; NEUROBLASTOMA; FUSION;
D O I：
10.1016/j.bmcl.2011.04.020
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is considered a promising therapeutic target for human cancers. We identified novel tetracyclic derivatives as potent ALK inhibitors. Among them, compound 27 showed strong cytotoxicity against KARPAS-299 with an IC(50) value of 21 nM and significant antitumor efficacy in ALK fusion-positive blood and solid cancer xenograft models in mice without body weight loss. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3788 / 3793
页数：6
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