The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Discovery, In Vivo Activity, and Mechanism of Action of a Small-Molecule p53 Activator
Open accessAbstract
We have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biological tools for the study of sirtuin function as well as their potential therapeutic interest.
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Cites
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295
Sirtuins in aging and age-related disease
Longo, V. D., & Kennedy, B. K. (2006) · Cell · doi:10.1016/j.cell.2006.07.002 · Cited by 628
Different effects of p14ARF on the levels of ubiquitinated p53 and Mdm2 in vivo
Xirodimas, D., Saville, M. K., Edling, C., Lane, D. P., & Laín, S. (2001) · Oncogene · doi:10.1038/sj.onc.1204656 · Cited by 169
Self-citation
Cited by
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
Apoptosis in cancer: from pathogenesis to treatment
Wong, R. S. (2011) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-30-87 · Cited by 2,836
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085
Kruse, J.-P., & Gu, W. (2009) · Cell · doi:10.1016/j.cell.2009.04.050 · Cited by 1,610
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
Metadata
- Authors
- Lain, S., Hollick, J. J., Campbell, J., Staples, O. D., Higgins, M., Aoubala, M., McCarthy, A., Appleyard, V., Murray, K. E., Baker, L., Thompson, A., Mathers, J., Holland, S. J., Stark, M. J. R., Pass, G., Woods, J., Lane, D. P., & Westwood, N. J.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 13
- Issue
- 5
- Pages
- 454-463
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2140513990
- Cited by
- 522
- References
- 4
- FWCI
- 15.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Lain, S., Hollick, J. J., Campbell, J., Staples, O. D., Higgins, M., Aoubala, M., McCarthy, A., Appleyard, V., Murray, K. E., Baker, L., Thompson, A., Mathers, J., Holland, S. J., Stark, M. J. R., Pass, G., Woods, J., Lane, D. P., & Westwood, N. J. (2008). Discovery, In Vivo Activity, and Mechanism of Action of a Small-Molecule p53 Activator. Cancer Cell. https://doi.org/10.1016/j.ccr.2008.03.004
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
