Interaction between EGFR Mutant with Gefitinib

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Epidermal growth factor receptors (EGFR) are transmembrane receptor tyrosine kinases signaling crucial for cell proliferation. Mutations in the EGFR kinase domain are one of the most prevalent causes of clustered lung cancer, with 40% of mutations triggered by a mutation known as L858R. The L858R mutation occurs when a point substitution at exon 19 replaces leucine with arginine directly within the activation loop A of the kinase; Arg858 disrupts cell autoinhibitory interactions. Mutations at the active site can lead to severe problems, such as accelerating catalysis up to 50-fold, overexpression, or mutational malignancies in fibroblasts and lung epithelial cells. However, a number of tyrosine kinase inhibitors (TKI) have been developed and studied, with gefitinib being one of the first selective EGFR inhibitors targeting the ATP-binding cleft, interrupting signal transmission with high affinity towards the L858R mutation that holds promising outcomes for drug development.