Journal article

Preclinical analysis of the analinoquinazoline AG14781 a specific small molecule inhibitor of EGF receptor tyrosine kinase

AG Ellis, MM Doherty, F Walker, J Weinstock, M Nerrie, A Vitali, R Murphy, TG Johns, AM Scott, A Levitzki, G McLachlan, LK Webster, AW Burgessc, EC Nicec

Biochemical Pharmacology | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2006


The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is a potent and specific inhibitor of EGFR tyrosine kinase whose favourable preclinical profile supports progression towards clinical trials. Microphysiometric evaluation revealed a short (infinity) (r2=0.979) enabled the prediction of infusion rates and doses for sustained delivery using continuous 6 h infusions, where steady state was reached in 120 min. Plasma levels of AG1478>10 microM were achieved over the duration of the infusion. At the lowest dose, plasma drug levels after the cessation of infusion declined with a half-life of approximately 43 min. EGFR activity, measured both by autophosphorylation and downstream ..

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