Identification of Dual-Target Inhibitors for Epidermal Growth Factor Receptor and AKT: Virtual Screening Based on...

Area of Science:

• Computational chemistry and drug discovery
• Oncology and molecular targeted therapy

Background:

• Epidermal Growth Factor Receptor (EGFR) is a key target in non-small cell lung cancer (NSCLC).
• AKT protein inhibitors are utilized in various cancer therapies, including NSCLC treatment.
• Developing dual-target inhibitors for both EGFR and AKT presents a promising strategy for enhanced cancer treatment.

Purpose of the Study:

• To identify novel small molecular inhibitors targeting both EGFR and AKT.
• To explore potential dual-target inhibitors from the Chinese medicine (TCMIO) and human endogenous (HMDB) databases.

Main Methods:

• Utilized a ligand-based pharmacophore model for initial screening of EGFR inhibitors.
• Employed molecular docking and Molecular Dynamics (MD) simulations to assess binding affinities.
• Screened the immune-oncology Chinese medicine (TCMIO) and human endogenous (HMDB) databases.

Main Results:

• Identified TCMIO89212, TCMIO90156, and TCMIO98874 as compounds with significant binding free energies for both EGFR and AKT.
• HMDB0012243 demonstrated potential binding capabilities for both EGFR and AKT.
• These identified compounds show promise as dual-target inhibitors.

Conclusions:

• The study successfully identified potential dual-target inhibitors for EGFR and AKT from selected databases.
• The findings provide a valuable foundation for subsequent experimental validation and drug development.
• These novel inhibitors could offer new therapeutic strategies for non-small cell lung cancer.