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Discovery of CJ-2360 as a Potent and Orally Active Inhibitor of Anaplastic Lymphoma Kinase Capable of Achieving Complete Tumor Regression

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journal contribution
posted on 13.11.2020, 13:06 by Jianyong Chen, Yunlong Zhou, Xuyuan Dong, Liu Liu, Longchuan Bai, Donna McEachern, Sally Przybranowski, Chao-Yie Yang, Jeanne Stuckey, Xiaoqin Li, Bo Wen, Ting Zhao, Siwei Sun, Duxin Sun, Lingling Jiao, Yu Jing, Ming Guo, Dajun Yang, Shaomeng Wang
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.

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