Abstract
Epidermal growth factor receptors (EGFR) are the main focus of research for the novel cancer chemotherapy (e.g. Breast, lung, colon, and prostate) because of their fundamental role in cell proliferation, differentiation, metastasis and survival. The crystal structures of EGFR in complex with small molecule inhibitors have been used to explore key binding modes of the quinazoline moiety of the drugs inside the kinase hinge region. In this work, we performed structure-based virtual screening against a diverse set of ZINC database. Using pharmacophore modelling, with subsequent post-docking analyses, we found seven candidate compounds to pharmacophore-fit and docking score values higher than those of DJK_3021, EGFR-inhibitor. Binding mode analyses revealed that the way these compounds bind to EGFR is as same as that of the x-ray inhibitor, DJK_3021. The hydrophobic interaction is major in this binding mode beside a weak electrostatic interaction, including the hydrogen bond to Met793. Our results suggest that these molecules could be developed as novel lead compounds in anti-cancer drug design.