Bioinformatics study comparing the effectsof drugs and drug candidates effective on EGFR

The initiation of intracellular signals leading to cellular growth,division, and differentiation is facilitated by the epidermal growth factor receptor (EGFR). EGFR is composed of distinctstructural components, including an extracellular receptor domain,a transmembrane hydrophobic domain, and an intracellularkinase domain. This transmembrane protein functions as areceptor. Upon binding of a ligand to the EGFR protein, dimerizationoccurs, followed by tyrosine phosphorylation and theinitiation of intracellular signaling cascades. Increased expressionof either wild-type or mutant EGFR leads to cell proliferationand the activation of downstream signaling pathways thatare closely associated with the onset and progression of variouscancers. Due to its role as a resistance biomarker in tumors,EGFR has emerged as a promising target for the developmentof anticancer drugs. Consequently, EGFR is actively beingconsidered for use in the design and creation of such therapies.Tyrosine kinase inhibitors (TKIs) are designed to target EGFRby competing with ATP for binding to the kinase pocket. Uponbinding of TKIs to EGFR, phosphorylation is suppressed, leadingto the cessation of the EGFR signaling cascade.To conduct this study, a set of ۲۴ drug molecules and drugcandidates were initially extracted and optimized for energyusing HyperChem software. The EGFR protein structure wasobtained from www.Rcsb.org in two parts – extracellular andintracellular – and subsequently subjected to docking with eachof the ۲۴ molecules separately using Vina software.In this study, all ۲۴ molecules were found to affect the intracellulardomain of EGFR, with each molecule binding to thekinase pocket of the protein.Out of the ۲۴ molecules that were examined, Zanubrutinib, Alvocidib,and Abivertinib exhibited the strongest binding affinityto the EGFR protein kinase domain. This finding suggests thatthese three molecules could potentially be more effective thanthe other molecules studied in this research

کلیدواژه ها:

EGFR ، inhibitors ، cancer ، docking ، bioinformatics ، drug