Abstract
The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Drug Evaluation, Preclinical
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / chemistry
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ErbB Receptors / genetics
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Inhibitory Concentration 50
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Models, Molecular
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Molecular Conformation
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Mutation
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Quinolines / metabolism
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Quinolines / pharmacology*
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Quinolines
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ErbB Receptors