Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.

Abstract: The teachings relate to methods of identifying inhibitors of dimerization of tyrosine receptor kinases such as EGFR. The methods comprise providing, on a digital computer, a molecular model comprising a complex of extracellular dimerization domains of an RTK, docking a chemical databases to the molecular model, scoring the compounds comprised by the database, and identifying one or more high-scoring compounds. The methods further comprise testing a compound for RTK inhibitory activity in vitro, and testing a compound for specificity as an RTK inhibitor. Also disclosed are compounds selected by the described methods, and methods of treatment using the compounds. Two compounds (NSC11241 and NSC56452) are disclosed that inhibit EGF receptor kinase activation in a dose-dependent manner.