In silico design of EGFR^{L858R/T790M/C797S} inhibitors via 3D-QSAR, molecular docking, ADMET properties and molecular dynamics simulations.

ABSTRACT: The development of L858R/T790M/C797S mutations in EGFR is one of the main reasons for the emergence of resistance after third-generation treatment of non-small cell lung cancer (NSCLC). Therefore, the development of 4th generation drugs needs urgent attention. To overcome resistance, in silico drug discovery and Design approaches were employed on a library of 29 novel 9-heterocyclyl substituted 9H-purines derivatives with EGFR^{L858R/T790M/C797S} inhibition for anticancer activity against NSCLC. The COMSIA/EHA model (Q² = 0.584, R² = 0.816, and Rpred2 = 0.73) showed a stable and reliable predictive ability of NSCLC activity, which was tested by several validation methods. Molecular docking studies reveal crucial interactions with EGFR^{L858R/T790M/C797S}

SUBMITTER: Hadni H 

PROVIDER: S-EPMC9674911 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature