How Different Substitution Positions of F, Cl Atoms in Benzene Ring of 5-Methylpyrimidine Pyridine Derivatives Affect the Inhibition Ability of EGFR^{L858R/T790M/C797S} Inhibitors: A Molecular Dynamics Simulation Study.

ABSTRACT: Lung cancer is the most frequent cause of cancer-related deaths worldwide, and mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are a common cause of non-small-cell lung cancers, which is a major subtype of lung cancers. Recently, a series of 5-methylpyrimidine-pyridinone derivatives have been designed and synthesized as novel selective inhibitors of EGFR and EGFR mutants. However, the binding-based inhibition mechanism has not yet been determined. In this study, we carried out molecular dynamic simulations and free-energy calculations for EGFR derivatives to fill this gap. Based on the investigation, the three factors that influence the inhibitory effect of inhibitors are as follows: (1) The substitution site of the Cl atom is the main factor influencing the a

SUBMITTER: E J 

PROVIDER: S-EPMC7071101 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature