Abstract |
Pancreatic carcinoma is the fourth leading cause of death from cancer. Novel targets and therapeutic options are needed to aid in the treatment of pancreatic cancer. The compound UA62784 is a novel fluorenone with inhibitory activity against the centromere protein E (CENP-E) kinesin-like protein. UA62784 was isolated due to its selectivity in isogenic pancreatic carcinoma cell lines with a deletion of the DPC4 gene. UA62784 causes mitotic arrest by inhibiting chromosome congression at the metaphase plate likely through inhibition of the microtubule-associated ATPase activity of CENP-E. Furthermore, CENP-E binding to kinetochores during mitosis is not affected by UA62784, suggesting that the target lies within the motor domain of CENP-E. UA62784 is a novel specific inhibitor of CENP-E and its activity suggests a potential role for antimitotic drugs in treating pancreatic carcinomas.
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Authors | Meredith C Henderson, Yeng-Jeng Y Shaw, Hong Wang, Haiyong Han, Laurence H Hurley, Gary Flynn, Robert T Dorr, Daniel D Von Hoff |
Journal | Molecular cancer therapeutics
(Mol Cancer Ther)
Vol. 8
Issue 1
Pg. 36-44
(Jan 2009)
ISSN: 1535-7163 [Print] United States |
PMID | 19139111
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Chromosomal Proteins, Non-Histone
- Oxazoles
- Tubulin
- UA 62784
- Xanthones
- centromere protein E
- Kinesins
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Topics |
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Chromosomal Proteins, Non-Histone
(antagonists & inhibitors, metabolism)
- Humans
- Kinesins
(antagonists & inhibitors, classification, metabolism)
- Microtubules
(drug effects, metabolism)
- Molecular Structure
- Oxazoles
(chemistry, pharmacology)
- Protein Binding
- Tubulin
(metabolism)
- Xanthones
(chemistry, pharmacology)
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