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 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.
authors.affiliation: Arizona Cancer Center, BIO5 Institute, College of Pharmacy, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724-5024, USA.
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Henderson
authors.forename: Yeng-Jeng Y
authors.initials: YJ
authors.lastname: Shaw
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Haiyong
authors.initials: H
authors.lastname: Han
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Hurley
authors.forename: Gary
authors.initials: G
authors.lastname: Flynn
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dorr
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: 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*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D010080:Oxazoles; D014404:Tubulin; C535156:UA 62784; D044004:Xanthones; C068688:centromere protein E; D016547:Kinesins