Computational modeling study identifies novel lead molecules targeting active and inactive EGFR conformations, highlighting potential candidates for inhibiting oncogenic kinase activity.
Epidermal growth factor receptor (EGFR) is a transmembrane protein belonging to the receptor tyrosine kinase (RTK) superfamily, reported as a promising anticancer target in treating diverse malignancies. Previous studies on microarray gene expression and methylation status in cell and animal models revealed the differential expression of EGFR at the early stages of cellular transformation. Additionally, an unpublished study of methylation analysis of EGFR gene promoters conducted in human cancer-related samples showed a several-fold increase in EGFR gene expression, suggesting epigenetic upregulation in tumors. Considering these findings, in the present study, we selected inactive (DFGout) (D: aspartic acid, F: phenylalanine, G: glycine) and active (DFGin) confirmations of EGFR to identify novel lead molecules against aberrant EGFR activity in cancer. Extra precision (XP) docking, molecular mechanics/generalized born surface area (MM/GBSA), molecular dynamics (MD) simulations, and ADME/T were performed, and the results showed that the lead 1 molecule of each target exhibited a better binding affinity and favorable stability than the existing ligands.
No takes yet. Share an insight, caveat, or question.
Jannu et al. (2025) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: