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2000
Volume 21, Issue 19
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Objective

The current use of Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) inhibitors is often limited by low selectivity and adverse side effects, highlighting the urgent need for novel, highly selective agents targeting this receptor.

Methods

Based on existing VEGFR-2 inhibitors, we employed computer-aided drug design (CADD) techniques to develop a virtual compound library using active docking fragments. Molecular docking was performed using the configuration of VEGFR-2 as the receptor protein(PDB:4ASD). Comparative analysis and screening identified the most promising inhibitor, which was subsequently validated through molecular dynamics simulations.

Results

From the virtual library, 10 potential highly active inhibitors were identified. In particular, Compound demonstrated strong binding affinity with the protein configuration, forming four hydrogen bonds during docking. The calculated CODOCKER energy was 39.7315 kcal/mol, with an RMSD of 0.4634 nm and RMSF of 0.3234 nm. Compared to Sorafenib, Compound exhibited superior docking selectivity and activity.

Conclusion

Computational analyses suggest that Compound is a promising candidate as a highly selective VEGFR-2 inhibitor. Nonetheless, due to the inherent limitations of in silico docking studies, further chemical synthesis and experimental biological validation are required to confirm its potential.

© 2024 Bentham Science Publishers
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2025-01-27
2025-09-08

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Design of VEGFR2 Inhibitors: Construction and Screening of Virtual Compound Libraries
Letters in Drug Design & Discovery 21, 4709 (2024); https://doi.org/10.2174/0115701808334488241121054542
/content/journals/lddd/10.2174/0115701808334488241121054542
/content/journals/lddd/10.2174/0115701808334488241121054542
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  • Article Type:     Research Article
Keyword(s): computer-aided drug design; molecular docking; molecular dynamics simulation; receptor tyrosine kinases; VEGFR-2 inhibitor; virtual compound library

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