Compounds found in Cannabis sativa showed promising predicted binding to epidermal growth factor receptor (EGFR), a protein that promotes tumour-cell proliferation when overexpressed. Using computer-based screening, researchers identified luteolin-7-O-glucoside, grossamide, and quercetin as leading candidates for blocking the receptor’s kinase domain—a target in lung cancer treatment.
During 100-nanosecond molecular dynamics simulations, quercetin formed the most structurally stable EGFR complex. Grossamide produced the most favourable calculated binding free energy, exceeding the reference drug gefitinib in this computational measure. The leading compounds also showed favourable predicted pharmacokinetic profiles.
These findings highlight cannabis plant compounds as candidates for developing therapies that target EGFR.
“Lung cancer remains a major global health burden, and epidermal growth factor receptor (EGFR) overexpression promotes tumour-cell proliferation, making EGFR an important therapeutic target.
This study used an in-silico approach to evaluate Cannabis sativa compounds as inhibitors of the EGFR kinase domain.
Among the compounds investigated, Luteolin-7 -O- glucoside, grossamide, and quercetin were the leading ATP-competitive inhibitors, with binding affinities of -10.878, -10.091, and – 10.000 kcal/mol, respectively. A four-feature pharmacophore model was generated from the lead compounds, which also showed favourable predicted pharmacokinetic profiles.
During 100-ns molecular dynamics simulations (MDS), the EGFR-quercetin complex exhibited the lowest root mean square deviation of 0.9-1.5 Å, while fluctuation profiles revealed a relatively stable ligand-bound complex compared with the apo-EGFR. The MDS trajectory Molecular Mechanics/Generalized Born Surface Area analysis yielded binding free energies of -75.59 kcal/mol for grossamide, -56.90 kcal/mol for isovitexin, -49.11 kcal/mol for luteolin-7 -O- glucoside, and – 43.27 kcal/mol for quercetin, compared with – 47.41 kcal/mol for gefitinib. Electronic profiling revealed favourable orbital overlap and softness for quercetin and flavone glycosides within EGFR, while isovitexin showed superior kinetic stability and balanced solvation, supporting strong binding and active-site entry.
These findings identify luteolin-7 -O- glucoside, grossamide, and quercetin as promising EGFR inhibitors and provide a baseline hypothesis for experimental validation.”