The uncontrolled growth of cancer cells is caused by their innate tendency to multiply without limits. In addition to colonizing adjacent tissues, they are capable of forming aggregates in isolated anatomical sites, thereby significantly increasing their invasiveness. Over time, malignant tumors that progressively destroy essential tissues and organs are ultimately lethal. It is well known that growth factor-driven signaling influence malignancy. The transmembrane receptor tyrosine kinases of growth factors influence the survival, differentiation, and proliferation of cells. To expedite cell division, neurotransmitters and proteins resembling epidermal growth factor (EGF) stimulate EGF receptor (EGFR) family members including HER2-4 and EGFR. The development and growth of numerous varieties of human cancer cells, as well as the morphogenesis of numerous animal species (nematodes to humans), are influenced by this signaling module, which is remarkably conserved. The EGFR family, consisting of over thirty ligands and four receptors, forms a complex and advanced human signal transduction network. The T790M mutation in the EGFR kinase enhances treatment resistance by increasing the affinity for ATP. This work used a molecular design tool to evaluate quinazoline derivatives with the highest IC50 values against EGFR and analyze the molecular interactions in the binding site. The goal was to uncover novel compounds with promising potential.
Key words: Quinazoline, Computer aided drug design, EGFR, T790M, Molecular docking
|
