Article
Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR).
Journal of medicinal chemistry - 12 Sept 2013
Ward Richard A, Anderton Mark J, Ashton Susan, Bethel Paul A, Box Matthew, Butterworth Sam, Colclough Nicola, Chorley Christopher G, Chuaqui Claudio, Cross Darren A E, Dakin Les A, Debreczeni Judit É, Eberlein Cath, Finlay M Raymond V, Hill George B, Grist Matthew, Klinowska Teresa C M, Lane Clare, Martin Scott, Orme Jonathon P, Smith Peter, Wang Fengjiang, Waring Michael J
Abstract excerpt
A novel series of small-molecule inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by molecular modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond...
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