1256579-01-7Relevant articles and documents
9-substituted 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles as highly selective and potent anaplastic lymphoma kinase inhibitors
Kinoshita, Kazutomo,Kobayashi, Takamitsu,Asoh, Kohsuke,Furuichi, Noriyuki,Ito, Toshiya,Kawada, Hatsuo,Hara, Sousuke,Ohwada, Jun,Hattori, Kazuo,Miyagi, Takuho,Hong, Woo-Sang,Park, Min-Jeong,Takanashi, Kenji,Tsukaguchi, Toshiyuki,Sakamoto, Hiroshi,Tsukuda, Takuo,Oikawa, Nobuhiro
, p. 6286 - 6294 (2011)
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 E0 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 IC50 value of 2.9 nM and strong antiproliferative activity against KARPAS-299 with an IC50 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.
