Discovery of CJ-2360 as a Potent and Orally Active Inhibitor of Anaplastic Lymphoma Kinase Capable of Achieving Complete Tumor Regression
Jianyong Chen, Yunlong Zhou, Xuyuan Dong, Liu Liu, Longchuan Bai, Donna McEachern, Sally Przybranowski, Chao‐Yie Yang, Jeanne A. Stuckey, Xiaoqin Li, Bo Wen, Ting C. Zhao, Siwei Sun, Duxin Sun, Lingling Jiao, Yu Jing, Ming‐Lei Guo, Dajun Yang, Shaomeng Wang
Abstract
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.