1159577-23-7Relevant academic research and scientific papers
Discovery of CJ-2360 as a Potent and Orally Active Inhibitor of Anaplastic Lymphoma Kinase Capable of Achieving Complete Tumor Regression
Chen, Jianyong,Zhou, Yunlong,Dong, Xuyuan,Liu, Liu,Bai, Longchuan,McEachern, Donna,Przybranowski, Sally,Yang, Chao-Yie,Stuckey, Jeanne,Li, Xiaoqin,Wen, Bo,Zhao, Ting,Sun, Siwei,Sun, Duxin,Jiao, Lingling,Jing, Yu,Guo, Ming,Yang, Dajun,Wang, Shaomeng
, p. 13994 - 14016 (2020)
We report herein the discovery of a class of potent small-molecule inhibitors of anaplastic lymphoma kinase (ALK) containing a fused indoloquinoline scaffold. The most promising compound CJ-2360 has an IC50 value of 2.2 nM against wild-type ALK and low-nanomolar potency against several clinically reported ALK mutants. This compound is capable of achieving complete tumor regression in the ALK-positive KARPAS-299 xenograft model with oral administration in mice. CJ-2360 represents a promising ALK inhibitor for advanced preclinical development.
Structural optimization and biological evaluation of 2-substituted 5-hydroxyindole-3-carboxylates as potent inhibitors of human 5-lipoxygenase
Karg, Eva-Maria,Luderer, Susann,Pergola, Carlo,Bühring, Ulrike,Rossi, Antonietta,Northoff, Hinnak,Sautebin, Lidia,Troschütz, Reinhard,Werz, Oliver
supporting information; experimental part, p. 3474 - 3483 (2010/03/25)
Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5- hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 μM, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 μM) and significantly prevented leukotriene B4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics.
