UA62784, a novel inhibitor of centromere protein E kinesin-like protein
- Mol Cancer Ther. 2009 Jan;8(1):36-44. doi: 10.1158/1535-7163.MCT-08-0789.
- 1. Arizona Cancer Center, BIO5 Institute, College of Pharmacy, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724-5024, USA.
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.