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Updated: Mar 22, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Discovery of Novel Human Epidermal Growth Factor Receptor-2 Inhibitors by Structure-based Virtual Screening
Zheng Shi1, Tian Yu1, Rong Sun2
1Department of Basic Medicine, School of Medicine and Nursing, Sichuan Industrial Institute of Antibiotics, Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Chengdu University, Chengdu 610015, China.
Background:
Human epidermal growth factor receptor-2 (HER2) is a trans-membrane receptor like protein, and aberrant signaling of HER2 is implicated in many human cancers, such as ovarian cancer, gastric cancer, and prostate cancer, most notably breast cancer. Moreover, it has been in the spotlight in the recent years as a promising new target for therapy of breast cancer.
Objective:
Since virtual screening has become an integral part of the drug discovery process, it is of great significant to identify novel HER2 inhibitors by structure-based virtual screening.
Materials And Methods:
In this study, we carried out a series of elegant bioinformatics approaches, such as virtual screening and molecular dynamics (MD) simulations to identify HER2 inhibitors from Food and Drug Administration-approved small molecule drug as potential "new use" drugs.
Results:
Molecular docking identified top 10 potential drugs which showed spectrum affinity to HER2. Moreover, MD simulations suggested that ZINC08214629 (Nonoxynol-9) and ZINC03830276 (Benzonatate) might exert potential inhibitory effects against HER2-targeted anti-breast cancer therapeutics.
Conclusion:
Together, our findings may provide successful application of virtual screening studies in the lead discovery process, and suggest that our discovered small molecules could be effective HER2 inhibitor candidates for further study.
Summary:
A series of elegant bioinformatics approaches, including virtual screening and molecular dynamics (MD) simulations were took advantage to identify human epidermal growth factor receptor-2 (HER2) inhibitors. Molecular docking recognized top 10 candidate compounds, which showed spectrum affinity to HER2. Further, MD simulations suggested that ZINC08214629 (Nonoxynol-9) and ZINC03830276 (Benzonatate) in candidate compounds were identified as potential "new use" drugs against HER2-targeted anti-breast cancer therapeutics. Abbreviations used: HER2: Human epidermal growth factor receptor-2, FDA: Food and Drug Administration, PDB: Protein Database Bank, RMSDs: Root mean square deviations, SPC: Single point charge, PME: Particle mesh Ewald, NVT: Constant volume, NPT: Constant pressure, RMSF: Root-mean-square fluctuation.
Insights
This study used bioinformatics to find new uses for existing drugs as HER2 inhibitors. Nonoxynol-9 and Benzonatate show promise for breast cancer therapy.
Area of Science:
- Computational drug discovery
- Bioinformatics and cheminformatics
Background:
- Aberrant Human Epidermal Growth Factor Receptor-2 (HER2) signaling drives various cancers, notably breast cancer.
- HER2 is a key therapeutic target, especially in breast cancer treatment.
Purpose of the Study:
- To identify novel HER2 inhibitors using structure-based virtual screening.
- To repurpose Food and Drug Administration (FDA)-approved small molecules as potential HER2-targeted cancer therapeutics.
Main Methods:
- Employed virtual screening and molecular dynamics (MD) simulations.
- Utilized bioinformatics approaches to analyze drug-target interactions.
- Screened FDA-approved small molecules for HER2 affinity.
Main Results:
- Molecular docking identified 10 compounds with significant HER2 affinity.
- MD simulations indicated Nonoxynol-9 (ZINC08214629) and Benzonatate (ZINC03830276) as potential HER2 inhibitors.
- These compounds show promise for HER2-targeted anti-breast cancer therapies.
Conclusions:
- Virtual screening is effective for lead discovery in drug development.
- Nonoxynol-9 and Benzonatate are promising candidates for further investigation as HER2 inhibitors.
- The identified small molecules may offer new therapeutic strategies for HER2-driven cancers.
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