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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.

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.

SUBMITTER: Chen J

PROVIDER: S-EPMC8855370 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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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.

Chen Jianyong J Zhou Yunlong Y Dong Xuyuan X Liu Liu L Bai Longchuan L McEachern Donna D Przybranowski Sally S Yang Chao-Yie CY Stuckey Jeanne J Li Xiaoqin X Wen Bo B Zhao Ting T Sun Siwei S Sun Duxin D Jiao Lingling L Jing Yu Y Guo Ming M Yang Dajun D Wang Shaomeng S

Journal of medicinal chemistry 20201113 22

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 IC<sub>50</sub> 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 pro ...[more]

PMID: 33185101

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