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

Meredith C. Henderson; Yeng Jeng Y. Shaw; Hong Wang; Haiyong Han; Laurence H. Hurley; Gary Flynn; Robert T. Dorr; Daniel D. Von Hoff

doi:10.1158/1535-7163.MCT-08-0789

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

Meredith C. Henderson, Yeng Jeng Y. Shaw, Hong Wang, Haiyong Han, Laurence H. Hurley, Gary Flynn, Robert T. Dorr, Daniel D. Von Hoff

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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 duringmitosis 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.

Original language	English (US)
Pages (from-to)	36-44
Number of pages	9
Journal	Molecular Cancer Therapeutics
Volume	8
Issue number	1
DOIs	https://doi.org/10.1158/1535-7163.MCT-08-0789
State	Published - Jan 1 2009

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "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 duringmitosis 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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AU - Henderson, Meredith C.

AU - Shaw, Yeng Jeng Y.

AU - Wang, Hong

AU - Han, Haiyong

AU - Hurley, Laurence H.

AU - Flynn, Gary

AU - Dorr, Robert T.

AU - Von Hoff, Daniel D.

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Y1 - 2009/1/1

N2 - 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 duringmitosis 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.

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

Abstract

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