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UA62784, a novel inhibitor of centromere protein E kinesin-like protein.

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.

SUBMITTER: Henderson MC

PROVIDER: S-EPMC2634858 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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UA62784, a novel inhibitor of centromere protein E kinesin-like protein.

Henderson Meredith C MC Shaw Yeng-Jeng Y YJ Wang Hong H Han Haiyong H Hurley Laurence H LH Flynn Gary G Dorr Robert T RT Von Hoff Daniel D DD

Molecular cancer therapeutics 20090101 1

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 metaph ...[more]

PMID: 19139111

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