Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. In Silico Analysis of CDKs in Breast Cancer
2.2. THAL-SNS-032 Is Active in HER2-Positive Cell Lines
2.3. THAL-SNS-032 Is More Potent Than the Parental CDK9 Kinase Inhibitor
2.4. Effect of THAL-SNS-032 on the Cell Cycle
2.5. THAL-SNS-032 Induces Cell Death
2.6. THAL-SNS-032 Has an Inverse Therapeutic Index
3. Discussion
4. Materials and Methods
4.1. Clinical Outcome Evaluation
4.2. Cell Culture and Drugs
4.3. Proliferation Assay (MTT) and EC50 Value
4.4. Matrigel-3D Tumor Sphere-Forming Assay
4.5. Fibronectin-Adhesion Assay
4.6. Protein Expression Analysis: Western Blot
4.7. Flow Cytometry Experiments
4.8. Xenograft Mice (In Vivo)
4.9. Dependency Study and Cell Line Expression Analyses
4.10. Small Interfering RNA CDK9
4.11. Quantitative Reverse-Transcription PCR
4.12. CDKs Expression in Normal Tissues
4.13. Caspase 3 Activity
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Noblejas-López, M.d.M.; Gandullo-Sánchez, L.; Galán-Moya, E.M.; López-Rosa, R.; Tébar-García, D.; Nieto-Jiménez, C.; Gómez-Juárez, M.; Burgos, M.; Pandiella, A.; Ocaña, A. Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer. Int. J. Mol. Sci. 2022, 23, 5476. https://doi.org/10.3390/ijms23105476
Noblejas-López MdM, Gandullo-Sánchez L, Galán-Moya EM, López-Rosa R, Tébar-García D, Nieto-Jiménez C, Gómez-Juárez M, Burgos M, Pandiella A, Ocaña A. Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer. International Journal of Molecular Sciences. 2022; 23(10):5476. https://doi.org/10.3390/ijms23105476
Chicago/Turabian StyleNoblejas-López, María del Mar, Lucía Gandullo-Sánchez, Eva M. Galán-Moya, Raquel López-Rosa, David Tébar-García, Cristina Nieto-Jiménez, Mónica Gómez-Juárez, Miguel Burgos, Atanasio Pandiella, and Alberto Ocaña. 2022. "Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer" International Journal of Molecular Sciences 23, no. 10: 5476. https://doi.org/10.3390/ijms23105476