UA62784, a novel inhibitor of centromere protein E kinesin-like protein.
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.
Henderson
Meredith C
MC
Arizona Cancer Center, BIO5 Institute, College of Pharmacy, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724-5024, USA.
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
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
D002868:Chromosomal Proteins, Non-Histone; D010080:Oxazoles; D014404:Tubulin; C535156:UA 62784; D044004:Xanthones; C068688:centromere protein E; D016547:Kinesins