Reviving the guardian of the genome: Small molecule activators of p53
- PMID: 28351719
- PMCID: PMC5601031
- DOI: 10.1016/j.pharmthera.2017.03.013
Reviving the guardian of the genome: Small molecule activators of p53
Abstract
The tumor suppressor p53 is one of the most important proteins for protection of genomic stability and cancer prevention. Cancers often inactivate it by either mutating its gene or disabling its function. Thus, activating p53 becomes an attractive approach for the development of molecule-based anti-cancer therapy. The past decade and half have witnessed tremendous progress in this area. This essay offers readers with a grand review on this progress with updated information about small molecule activators of p53 either still at bench work or in clinical trials.
Keywords: Drug discovery; Inauhzin; MDM2; MDMX; Small molecules; p53.
Copyright © 2017 Elsevier Inc. All rights reserved.
Conflict of interest statement
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5601031/bin/nihms863163f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5601031/bin/nihms863163f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5601031/bin/nihms863163f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5601031/bin/nihms863163f4.gif)
Similar articles
-
Efficient reactivation of p53 in cancer cells by a dual MdmX/Mdm2 inhibitor.J Am Chem Soc. 2014 Dec 31;136(52):18023-33. doi: 10.1021/ja509223m. Epub 2014 Dec 17. J Am Chem Soc. 2014. Retraction in: J Am Chem Soc. 2015 Nov 18;137(45):14546. doi: 10.1021/jacs.5b11033. PMID: 25453499 Retracted.
-
Awakening the "guardian of genome": reactivation of mutant p53.Cancer Chemother Pharmacol. 2019 Jan;83(1):1-15. doi: 10.1007/s00280-018-3701-x. Epub 2018 Oct 15. Cancer Chemother Pharmacol. 2019. PMID: 30324219 Review.
-
Rescuing the guardian of the genome.Science. 2016 Oct 7;354(6308):26-28. doi: 10.1126/science.354.6308.26. Science. 2016. PMID: 27846480 No abstract available.
-
A balancing act: using small molecules for therapeutic intervention of the p53 pathway in cancer.Chem Soc Rev. 2020 Oct 5;49(19):6995-7014. doi: 10.1039/d0cs00163e. Chem Soc Rev. 2020. PMID: 32869798 Review.
-
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy.Annu Rev Pharmacol Toxicol. 2009;49:223-41. doi: 10.1146/annurev.pharmtox.48.113006.094723. Annu Rev Pharmacol Toxicol. 2009. PMID: 18834305 Free PMC article. Review.
Cited by
-
Glioblastoma Therapy: Past, Present and Future.Int J Mol Sci. 2024 Feb 21;25(5):2529. doi: 10.3390/ijms25052529. Int J Mol Sci. 2024. PMID: 38473776 Free PMC article. Review.
-
The Analysis of Selected miRNAs and Target MDM2 Gene Expression in Oral Squamous Cell Carcinoma.Biomedicines. 2023 Nov 14;11(11):3053. doi: 10.3390/biomedicines11113053. Biomedicines. 2023. PMID: 38002053 Free PMC article.
-
MicroRNA-215-5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2.Cancer Med. 2023 Jun;12(12):13455-13470. doi: 10.1002/cam4.5993. Epub 2023 May 3. Cancer Med. 2023. PMID: 37132262 Free PMC article.
-
Multifaceted role for p53 in pancreatic cancer suppression.Proc Natl Acad Sci U S A. 2023 Mar 7;120(10):e2211937120. doi: 10.1073/pnas.2211937120. Epub 2023 Feb 27. Proc Natl Acad Sci U S A. 2023. PMID: 36848578 Free PMC article.
-
Therapeutic Strategies to Activate p53.Pharmaceuticals (Basel). 2022 Dec 24;16(1):24. doi: 10.3390/ph16010024. Pharmaceuticals (Basel). 2022. PMID: 36678521 Free PMC article. Review.
References
-
- Amato I. Cancer therapy. Hope for a magic bullet that moves at the speed of light. Science. 1993;262(5130):32–33. News. - PubMed
-
- Andreeff M, Kelly KR, Yee K, Assouline S, Strair R, Popplewell L, et al. Kojima K. Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia. Clin Cancer Res. 2016;22(4):868–876. doi: 10.1158/1078-0432.CCR-15-0481. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous