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

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

  • J Med Chem. 2020 Nov 25;63(22):13994-14016. doi: 10.1021/acs.jmedchem.0c01550.
Jianyong Chen 1 2,  Yunlong Zhou 2,  Xuyuan Dong 1,  Liu Liu 1,  Longchuan Bai 1,  Donna McEachern 1,  Sally Przybranowski 1,  Chao-Yie Yang 1,  Jeanne Stuckey 3,  Xiaoqin Li 4,  Bo Wen 4,  Ting Zhao 4,  Siwei Sun 4,  Duxin Sun 4,  Lingling Jiao 2,  Yu Jing 2,  Ming Guo 2,  Dajun Yang 2,  Shaomeng Wang 1
Affiliations

Affiliations

  • 1 Rogel Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • 2 Ascentage Pharma (Jiangsu), Medical City Avenue, QB3 Building First Floor, Taizhou, Jiangsu Province 225300, China.
  • 3 Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • 4 Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
PMID: 33185101 DOI: 10.1021/acs.jmedchem.0c01550
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.

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