Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments
Abstract
:1. Introduction
2. Results
2.1. The Discovery of Potential SLC7A11/xCT Axis Inhibitors
2.2. In Vitro Evaluation of the Effect Compound 1 Has on the Oxidative/Antioxidant Balance within HeLa Cells or Similar
2.3. In Vitro Evaluation of the Inhibitory Effects of Compound 1 on HeLa Cell Migration at Low Concentrations
2.4. Assessment of the Toxic Effects of Compound 1 on HeLa Three-Dimensional Spheroids
2.5. Molecular Dynamics Simulations
2.5.1. Structural Mobility and Compactness of SLC7A11 Systems
2.5.2. Collective Motions of SLC7A11 Systems
2.5.3. Local Correlation Motion Patterns
2.5.4. Hydrogen Bond Analysis
2.5.5. K-Means Clustering Analysis
2.5.6. Free Energy Calculations
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Molecular Docking
4.3. Molecular Dynamics Simulations
4.4. Cell Culture
4.5. Cell Viability Assay
4.6. Cell Scratch Assay
4.7. Migration Assay
4.8. ROS Assay
4.9. Toxicity Assessment of 3D Tumor Spheroids
4.10. Calcein-AM Staining
4.11. Intracellular GSH Level Assay
4.12. Intracellular Glutamine Level Assay
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Yue, J.; Yin, Y.; Feng, X.; Xu, J.; Li, Y.; Li, T.; Liang, S.; He, X.; Liu, Z.; Wang, Y. Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments. Int. J. Mol. Sci. 2024, 25, 8284. https://doi.org/10.3390/ijms25158284
Yue J, Yin Y, Feng X, Xu J, Li Y, Li T, Liang S, He X, Liu Z, Wang Y. Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments. International Journal of Molecular Sciences. 2024; 25(15):8284. https://doi.org/10.3390/ijms25158284
Chicago/Turabian StyleYue, Jianda, Yekui Yin, Xujun Feng, Jiawei Xu, Yaqi Li, Tingting Li, Songping Liang, Xiao He, Zhonghua Liu, and Ying Wang. 2024. "Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments" International Journal of Molecular Sciences 25, no. 15: 8284. https://doi.org/10.3390/ijms25158284