structure-based identification of some potential epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) with in-silico assessment of their pharmacokinetic features and quantum chemical calculations

Epidermal growth factor receptor (egfr) belongs to the tyrosine kinase receptor family and plays a significant role in critical cellular procedures in many cancers. egfr was also identified as the main target for combating of tumor related-illness such as non-small cell lung cancer (nsclc). nsclc was the most common and lethal type of lung cancer, with nearly 1.8 million cases and less than 20% survival rate in every 5-years after diagnosis. this research aimed to identify potential egfr-tyrosine kinase inhibitors (tkis) using computer-aided techniques. the virtual screening executed identified compounds c4, c6, c14, and c26 as the hit compounds, with compound c6 as the best hit with moldock score: -138.245 kcal/mol, re-rank score: -116.868 and pose energy: -79.4185, respectively. all the identified hit egfr-tkis were seen to have a higher moldock score than the reference drug afatinib with a moldock score of -112.894 kcal/mol. based on the quantum chemical calculations, compound c4 was the most reactive among the hit, with a minor energy gap of 3.20 ev. the best hit egfr-tkis were ascertained to be drug-like and orally bioavailable due to their compliance with the filtering criteria used in evaluating their drug-likeness. furthermore, their average pharmacokinetic profiles were displayed based on their absorption, distribution, metabolism, excretion, and toxicity (admet) features. these hit egfr-tkis can serve as potential egfr-tkis because of their affinity towards egfr-tk receptor, reactivity, and safety.