PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6
Abstract
1. Background
2. Protein–Protein Interactions of E6
3. Therapeutic Targeting of E6 PPIs
3.1. E6–E6AP Interaction Inhibitors
3.2. E6–p53 Interaction Inhibitors
3.3. E6–Caspase 8 Interaction Inhibitors
3.4. Other Interaction Inhibitors
4. Progress and Limitations of Current E6 PPI Studies
5. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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PPI Targeted | Name of Inhibitor | Study Systems Utilized (In Silico, In Vitro, Cells, Animals) | Reported Potency (IC50/EC50) | References |
---|---|---|---|---|
E6–E6AP | Compound 9 | E6–E6AP filter plates | 17 µM (in vitro) | [61] |
Luteolin | E6–E6AP filter plates, CC cell lines | 23 µM (in vitro) | [62,63] | |
CAF-24 | E6–E6AP filter plates, CC cell lines | 5.2 µM (in vitro) | [62,63] | |
Gossypetin | E6–E6AP ELISA, PA-E6 cell line | 170 nM (in vitro) | [64] | |
Lig1, 2, 3 | E6–E6AP (in silico) | N/A | [65] | |
E6–p53 | Jaceosidin | E6–p53 ELISA, CC cell lines | N/A | [66] |
RITA | Pull-down, CC cell lines, xenograft | N/A | [67] | |
Nicandrenone | E6–p53 (in silico) | N/A | [68] | |
Compound 12 | E6–p53 in silico and ELISA, CC cells | 12–27 µM CC cells | [69] | |
E6–procaspase 8 | Myricetin | E6–Cas 8 AlphaScreen, CC cells | 0.6–0.9 µM (in vitro) | [70,71] |
Spinacine | E6–Cas 8 AlphaScreen, CC cells | 2 µM (in vitro) | [71] | |
GA-OH | E6-Cas 8 AlphaScreen, CC, and HNSCC * cells | N/A | [72] | |
E6–p300 | CH1iB | IP*, HNSCC* cells, xenograft | N/A | [75] |
CSS1477 | HNSCC cells, PD* xenograft | N/A | [ASCO] | |
E6–PDZ domain | Compounds 3, 4 | E6–PDZ (in silico) | N/A | [76] |
Fusicoccin | E6–14-3-3ζ X-ray, fluorescence polarization | N/A | [77] |
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Chitsike, L.; Duerksen-Hughes, P.J. PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6. Molecules 2021, 26, 3004. https://doi.org/10.3390/molecules26103004
Chitsike L, Duerksen-Hughes PJ. PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6. Molecules. 2021; 26(10):3004. https://doi.org/10.3390/molecules26103004
Chicago/Turabian StyleChitsike, Lennox, and Penelope J. Duerksen-Hughes. 2021. "PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6" Molecules 26, no. 10: 3004. https://doi.org/10.3390/molecules26103004
APA StyleChitsike, L., & Duerksen-Hughes, P. J. (2021). PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6. Molecules, 26(10), 3004. https://doi.org/10.3390/molecules26103004