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Updated: Aug 24, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Pharmacophore screening, molecular docking, and MD simulations for identification of VEGFR-2 and c-Met potential dual
1Phase Ⅰ Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Introduction:
The vascular endothelial growth factor receptor 2 (VEGFR-2) and the mesenchymal-epithelial transition factor (c-Met) are critical in the pathogenesis and progression of various cancers by synergistically contributing to angiogenesis and tumor progression. The development of dual-target inhibitors for VEGFR-2 and c-Met holds promise for more effective cancer therapies that could overcome tumor cell resistance, a limitation often observed with inhibitors targeting a single receptor.
Methods:
In this study, a computational virtual screening approach involving drug likeness evaluation, pharmacophore modeling and molecular docking was employed to identify VEGFR-2/c-Met dual-target inhibitors from ChemDiv database. Subsequent molecular dynamics (MD) simulations and MM/PBSA calculations were conducted to assess the stability of the protein-ligand interactions.
Results:
From the virtual screening process, 18 hit compounds were identified to exhibit potential inhibitory activity against VEGFR-2 and c-Met. Among them, compound17924 and compound4312 possessed the best inhibitory potential according to our screening criteria.
Discussion:
The analysis of the MD simulation results indicated that compound17924 and compound4312 showed superior binding free energies to both VEGFR-2 and c-Met when compared to the positive ligands. These findings suggested that both compounds were promising candidates for further drug development and could potentially serve as improved alternatives of cancer therapeutics.
Insights
Researchers identified novel dual-target inhibitors for vascular endothelial growth factor receptor 2 (VEGFR-2) and c-Met. These compounds show promise for developing more effective cancer therapies by targeting key pathways in tumor growth and angiogenesis.
Area of Science:
- Oncology
- Pharmacology
- Computational Chemistry
Background:
- Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) and mesenchymal-epithelial transition factor (c-Met) are crucial in cancer pathogenesis, angiogenesis, and tumor progression.
- Targeting these receptors individually can lead to tumor cell resistance, highlighting the need for dual-target inhibitors.
- Dual-target inhibitors offer a promising strategy for more effective cancer therapies.
Purpose of the Study:
- To identify novel dual-target inhibitors of VEGFR-2 and c-Met using computational methods.
- To evaluate the potential of identified compounds for overcoming resistance in cancer therapeutics.
- To explore new therapeutic strategies for various cancers by targeting key signaling pathways.
Main Methods:
- Employed computational virtual screening, including drug likeness evaluation, pharmacophore modeling, and molecular docking.
- Utilized molecular dynamics (MD) simulations and MM/PBSA calculations to assess protein-ligand interaction stability.
- Screened the ChemDiv database to identify potential dual-target inhibitors.
Main Results:
- Identified 18 hit compounds with potential inhibitory activity against both VEGFR-2 and c-Met.
- Compound 17924 and compound 4312 demonstrated the highest inhibitory potential based on screening criteria.
- MD simulations confirmed superior binding free energies for compounds 17924 and 4312 against both targets.
Conclusions:
- Compounds 17924 and 4312 are promising candidates for further drug development as VEGFR-2/c-Met dual-target inhibitors.
- These compounds could serve as improved alternatives to existing cancer therapeutics.
- The study validates a computational approach for discovering novel dual-target inhibitors for cancer treatment.
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