• Unlocking NSCLC Therapeutics: EGFR, miRNA, and Molecular Docking in Drug Discovery
  • Omid Rahbar Farzam,1 Ata Ollah Moghimi,2 Behzad Baradaran,3,*
    1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
    2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
    3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.


  • Introduction: Non-small cell lung cancer (NSCLC) represents a significant challenge in the field of oncology, necessitating novel therapeutic approaches for improved patient outcomes. This study explores the integration of microRNAs (miRNAs) and molecular docking techniques in the context of EGFR-targeted drug discovery for NSCLC. Epidermal Growth Factor Receptor (EGFR) has emerged as a pivotal player in NSCLC pathogenesis and a promising therapeutic target. MiRNAs, small non-coding RNA molecules, play a crucial role in regulating gene expression and are intricately connected to cancer-related signaling pathways. This research investigates the potential of miRNAs to modulate EGFR-related pathways, providing insights into their utility as therapeutic agents or targets. Molecular docking, a computational approach, is employed to analyze the interactions between miRNAs, EGFR, and potential drug candidates, offering a precise and efficient means of drug discovery. The results of this study shed light on innovative strategies for advancing NSCLC therapeutics, emphasizing the pivotal role of miRNAs and molecular docking in unlocking new avenues for drug development in the context of EGFR-targeted NSCLC treatment.
  • Methods: In our research, we undertook a molecular docking study involving the EGFR molecule and a set of 57 compounds. Initially, we accessed the three-dimensional (3D) structure of EGFR from the PDB database (PDB ID: 7jxq). Following this, we utilized Chimera 1.15 to remove any extraneous structural elements associated with our target molecule, thereby preparing it for the subsequent docking procedure. To create our unique ligands, we obtained compounds from the ZINC15 database, applying two specific filters: 'standard-ok' and 'world.' The 'standard-ok' filter encompassed substances with "standard" reactivity, including those adhering to PAINS and ZINC12 "clean" filters. Meanwhile, the 'world' filter comprised compounds that are approved drugs in major jurisdictions, including by the FDA (i.e., DrugBank approved). This comprehensive selection process yielded a total of 57 distinct molecules. Subsequently, we converted these molecules into formats conducive to analytical procedures using the Open Babel software. Leveraging the PyRx program, we conducted our docking experiments through the Vina Wizard console. Following the docking phase, we diligently scrutinized our results, employing rigorous criteria such as Binding Affinity and root mean square deviation (rmsd), both in the upper-bound (rmsd/ub) and lower-bound (rmsd/lb) contexts, to meticulously refine our selection of compounds. We employed the miRDB website to identify ten miRNAs with the most elevated target scores for targeting EGFR.
  • Results: Considering the Binding Affinity and root mean square deviation (rmsd) metrics, we found that the three medications, namely, Imatinib, Ebastine, and Ibrutinib, demonstrated the most favorable outcomes. Remarkably, these results even surpassed the performance of the three officially approved drugs Vandetanib, Erlotinib, and Gefitinib in our evaluation.The miRNAs with the most elevated target scores are comprised of the following 10 : hsa-miR-141-5p, hsa-miR-6878-5p, hsa-miR-514a-3p, hsa-miR-4533, hsa-miR-514b-3p, hsa-miR-6867-5p, hsa-miR-7157-3p, hsa-miR-6737-3p, hsa-miR-7110-3p, hsa-miR-9985
  • Conclusion: In the pursuit of enhanced therapeutics for non-small cell lung cancer (NSCLC), this study has unveiled a multifaceted approach that integrates microRNAs (miRNAs), molecular docking, and the targeting of the EGFR. NSCLC, a formidable oncological challenge, demands innovative strategies to improve patient outcomes, and our research has contributed to this endeavor. The findings of this study emphasize the pivotal role of miRNAs in modulating EGFR-related pathways, providing valuable insights into their potential as therapeutic agents or targets in NSCLC treatment. The integration of molecular docking techniques has enabled a deeper understanding of the intricate interactions between miRNAs, EGFR, and potential drug candidates, facilitating the rational design and optimization of novel therapeutics.
  • Keywords: NSCLC, EGFR, miRNA, Molecular Docking, Drug Discovery