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Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase
Open accessAbstract
Increased Aurora A expression occurs in a variety of human cancers and induces chromosomal abnormalities during mitosis associated with tumor initiation and progression. MLN8054 is a selective small-molecule Aurora A kinase inhibitor that has entered Phase I clinical trials for advanced solid tumors. MLN8054 inhibits recombinant Aurora A kinase activity in vitro and is selective for Aurora A over the family member Aurora B in cultured cells. MLN8054 treatment results in G 2 /M accumulation and spindle defects and inhibits proliferation in multiple cultured human tumor cells lines. Growth of human tumor xenografts in nude mice was dramatically inhibited after oral administration of MLN8054 at well tolerated doses. Moreover, the tumor growth inhibition was sustained after discontinuing MLN8054 treatment. In human tumor xenografts, MLN8054 induced mitotic accumulation and apoptosis, phenotypes consistent with inhibition of Aurora A. MLN8054 is a selective inhibitor of Aurora A kinase that robustly inhibits growth of human tumor xenografts and represents an attractive modality for therapeutic intervention of human cancers.
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Cited by
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
Macůrek, L., Lindqvist, A., Lim, D., Lampson, M. A., Klompmaker, R., Freire, R., Clouin, C., Taylor, S. S., Yaffe, M. B., & Medema, R. H. (2008) · Nature · doi:10.1038/nature07185 · Cited by 710
Shared and separate functions of polo-like kinases and aurora kinases in cancer
Lens, S. M. A., Voest, E. E., & Medema, R. H. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2964 · Cited by 597
A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment
Hyer, M. L., Milhollen, M. A., Ciavarri, J., Fleming, P., Traore, T., Sappal, D., Huck, J., Shi, J., Gavin, J., Brownell, J., et al. (2018) · Nature Medicine · doi:10.1038/nm.4474 · Cited by 447
Self-citationAurora A kinase (AURKA) in normal and pathological cell division
Nikonova, A. S., Astsaturov, I., Serebriiskii, I. G., Dunbrack, R. L., & Golemis, E. A. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1073-7 · Cited by 448
Aurora-A: the maker and breaker of spindle poles
Barr, A. R., & Gergely, F. (2007) · Journal of Cell Science · doi:10.1242/jcs.013136 · Cited by 441
Metadata
- Authors
- Manfredi, M. G., Ecsedy, J. A., Meetze, K. A., Balani, S. K., Burenkova, O., Chen, W., Galvin, K. M., Hoar, K. M., Huck, J. J., LeRoy, P. J., Ray, E. T., Sells, T. B., Stringer, B., Stroud, S. G., Vos, T. J., Weatherhead, G. S., Wysong, D. R., Zhang, M., Bolen, J. B., & Claiborne, C. F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-03-06
- Volume
- 104
- Issue
- 10
- Pages
- 4106-4111
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2064261028
- Cited by
- 413
- References
- 0
- FWCI
- 17.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Manfredi, M. G., Ecsedy, J. A., Meetze, K. A., Balani, S. K., Burenkova, O., Chen, W., Galvin, K. M., Hoar, K. M., Huck, J. J., LeRoy, P. J., Ray, E. T., Sells, T. B., Stringer, B., Stroud, S. G., Vos, T. J., Weatherhead, G. S., Wysong, D. R., Zhang, M., Bolen, J. B., & Claiborne, C. F. (2007). Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0608798104
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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