Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface
Abstract
:1. Introduction
2. Results
2.1. X-Ray Crystallographic Structure Analysis and Virtual Screening
2.2. In Vitro and in Cellulo Binding Assays
3. Materials and Methods
3.1. Molecular Modelling
3.2. Chemicals
3.3. Binding Tests
3.3.1. Thermal Shift Assay
3.3.2. Microscale Thermophoresis
3.4. Biology
3.4.1. Cell Cultures
3.4.2. Luciferase Reporter Assay
3.4.3. mRNA Expression
4. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Compound | ΔTm (°C) a | Kd (μM) b | % Luciferase Activity c |
---|---|---|---|
1 | 4.2 | 392 | 103 ± 5 |
2 | 3.4 | 650 | 36 ± 2 |
3 | 4.1 | 363 | 80 ± 5 |
4 | 0.6 | n. d. | 100 ± 5 |
Niflumic acid | 3.5 | n. d. | 86 ± 3 |
5 | 1.5 | n. d. | 86 ± 5 |
6 | 0.1 | n. d. | 103 ± 9 |
7 | 0.1 | n. d. | 94 ± 6 |
8 | 0.3 | n. d. | 103 ± 4 |
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Gibault, F.; Coevoet, M.; Sturbaut, M.; Farce, A.; Renault, N.; Allemand, F.; Guichou, J.-F.; Drucbert, A.-S.; Foulon, C.; Magnez, R.; et al. Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface. Cancers 2018, 10, 140. https://doi.org/10.3390/cancers10050140
Gibault F, Coevoet M, Sturbaut M, Farce A, Renault N, Allemand F, Guichou J-F, Drucbert A-S, Foulon C, Magnez R, et al. Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface. Cancers. 2018; 10(5):140. https://doi.org/10.3390/cancers10050140
Chicago/Turabian StyleGibault, Floriane, Mathilde Coevoet, Manon Sturbaut, Amaury Farce, Nicolas Renault, Frédéric Allemand, Jean-François Guichou, Anne-Sophie Drucbert, Catherine Foulon, Romain Magnez, and et al. 2018. "Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface" Cancers 10, no. 5: 140. https://doi.org/10.3390/cancers10050140