1346818-07-2Relevant academic research and scientific papers
Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib
Huang, Qinhua,Johnson, Ted W.,Bailey, Simon,Brooun, Alexei,Bunker, Kevin D.,Burke, Benjamin J.,Collins, Michael R.,Cook, Andrew S.,Cui, J. Jean,Dack, Kevin N.,Deal, Judith G.,Deng, Ya-Li,Dinh, Dac,Engstrom, Lars D.,He, Mingying,Hoffman, Jacqui,Hoffman, Robert L.,Johnson, Patrick S.,Kania, Robert S.,Lam, Hieu,Lam, Justine L.,Le, Phuong T.,Li, Qiuhua,Lingardo, Laura,Liu, Wei,Lu, Melissa West,McTigue, Michele,Palmer, Cynthia L.,Richardson, Paul F.,Sach, Neal W.,Shen, Hong,Smeal, Tod,Smith, Graham L.,Stewart, Albert E.,Timofeevski, Sergei,Tsaparikos, Konstantinos,Wang, Hui,Zhu, Huichun,Zhu, Jinjiang,Zou, Helen Y.,Edwards, Martin P.
, p. 1170 - 1187 (2014/03/21)
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).
HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES
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Page/Page column 80-81, (2011/11/30)
The invention relates to compounds of Formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases in which ALK protein is involved or in which inhibition of ALK activity may induce benefit, especially for the treatment of cancer mediated by a mutated EML4-ALK fusion protein.
