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 ۱.۸ million cases and less than ۲۰% survival rate in every ۵-years after diagnosis. This research aimed to identify potential EGFR-tyrosine kinase inhibitors (TKIs) using computer-aided techniques. The virtual screening executed identified compounds C۴, C۶, C۱۴, and C۲۶ as the hit compounds, with compound C۶ as the best hit with MolDock score: -۱۳۸.۲۴۵ kcal/mol, re-rank score: -۱۱۶.۸۶۸ and pose energy: -۷۹.۴۱۸۵, 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 -۱۱۲.۸۹۴ kcal/mol. Based on the quantum chemical calculations, compound C۴ was the most reactive among the hit, with a minor energy gap of ۳.۲۰ 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.

کلیدواژه ها:

Structure-based ، EGFR-TKIs ، pharmacokinetics ، Quantum chemical calculations