Zhou, Wenjun; Ercan, Dalia; Chen, Liang; Yun, Cai-Hong; Li, Danan; Capelletti, Marzia; Cortot, Alexis B.; Chirieac, Lucian; Iacob, Roxana E.; Padera, Robert; Engen, John R.; Wong, Kwok-Kin; Eck, Michael J.; Gray, Nathanael S.; Janne, Pasi A. published their research in Nature (London, United Kingdom) on December 31 ,2009. The article was titled 《Novel mutant-selective EGFR kinase inhibitors against EGFR T790M》.HPLC of Formula: 1213269-26-1 The article contains the following contents:
The clin. efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clin. more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacol. screens against clin. important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors. In addition to this study using 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine, there are many other studies that have used 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1HPLC of Formula: 1213269-26-1) was used in this study.
4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.HPLC of Formula: 1213269-26-1
Referemce:
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