Repurposing drugs for EGFR-targeted cancer therapy: An in silico and in vitro study with pharmacophore-based insights
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, cilt.144, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 144
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jmgm.2026.109288
- Dergi Adı: JOURNAL OF MOLECULAR GRAPHICS & MODELLING
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, EMBASE, INSPEC, MEDLINE
- İstanbul Üniversitesi Adresli: Hayır
Özet
Cancer is the second leading cause of death globally and remains a priority due to its impact on life quality, treatment complexity, and high costs. To expedite drug development, researchers are increasingly repurposing FDA-approved drugs and clinical candidates, reducing time and costs through in silico methods. In this study, 3235 FDA-approved and clinical molecules were screened for EGFR inhibition, a significant target due to its role in cancer progression and treatment resistance. A pharmacophore model was generated based on erlotinib's cocrystallized structure and quantitative structure-activity relationships. Molecules meeting the pharmacophoric criteria underwent SP and XP docking, with thresholds of -6.00 kcal/mol and -7.00 kcal/mol, respectively, followed by anti-cancer potential analysis via MetaCore/MetaDrug and MD simulations at 1, 10, and 100 ns to assess EGFR-binding stability. For the molecule Ticagrelor, which demonstrated particularly promising results, and Erlotinib cell culture viability assays were conducted across three cell lines-cancerous A549, U87, and healthy BEAS-2B- (IC50) of, 8.2576 mu M, 9.4058 mu M, and 15.893 mu M, respectively for Ticagrelor and 11.708 mu M, 12.747 mu M and 14.6709 mu M, respectively for Erlotinib. In silico results highlight Ticagrelor's significant EGFRinhibiting potential with enhanced binding stability compared to the reference.