| Literature DB >> 21823617 |
Kazutomo Kinoshita1, Takamitsu Kobayashi, Kohsuke Asoh, Noriyuki Furuichi, Toshiya Ito, Hatsuo Kawada, Sousuke Hara, Jun Ohwada, Kazuo Hattori, Takuho Miyagi, Woo-Sang Hong, Min-Jeong Park, Kenji Takanashi, Toshiyuki Tsukaguchi, Hiroshi Sakamoto, Takuo Tsukuda, Nobuhiro Oikawa.
Abstract
9-Substituted 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles were discovered as highly selective and potent anaplastic lymphoma kinase (ALK) inhibitors by structure-based drug design. The high target selectivity was achieved by introducing a substituent close to the E(0) region of the ATP binding site, which has a unique amino acid sequence. Among the identified inhibitors, compound 13d showed highly selective and potent inhibitory activity against ALK with an IC(50) value of 2.9 nM and strong antiproliferative activity against KARPAS-299 with an IC(50) value of 12.8 nM. The compound also displayed significant antitumor efficacy in an established ALK fusion gene-positive anaplastic large-cell lymphoma (ALCL) xenograft model in mice without body weight loss.Entities:
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Year: 2011 PMID： 21823617 DOI： 10.1021/jm200652u
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446