| Literature DB >> 24432909 |
Qinhua Huang1, Ted W Johnson, Simon Bailey, Alexei Brooun, Kevin D Bunker, Benjamin J Burke, Michael R Collins, Andrew S Cook, J Jean Cui, Kevin N Dack, Judith G Deal, Ya-Li Deng, Dac Dinh, Lars D Engstrom, Mingying He, Jacqui Hoffman, Robert L Hoffman, Patrick S Johnson, Robert S Kania, Hieu Lam, Justine L Lam, Phuong T Le, Qiuhua Li, Laura Lingardo, Wei Liu, Melissa West Lu, Michele McTigue, Cynthia L Palmer, Paul F Richardson, Neal W Sach, Hong Shen, Tod Smeal, Graham L Smith, Albert E Stewart, Sergei Timofeevski, Konstantinos Tsaparikos, Hui Wang, Huichun Zhu, Jinjiang Zhu, Helen Y Zou, Martin P Edwards.
Abstract
Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e, which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclinical pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).Entities:
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Year: 2014 PMID： 24432909 DOI： 10.1021/jm401805h
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446