Initial testing of the CENP-E inhibitor GSK923295A by the pediatric preclinical testing program.

ABSTRACT:

Background

The centromere kinesin motor protein CENP-E plays a crucial role in mitosis, and is an appealing molecular target in cancer. GSK923295A is an allosteric inhibitor of CENP-E that is undergoing clinical evaluation.

Procedures

GSK923295A was evaluated against the 23 cell lines in the Pediatric Preclinical Testing Program (PPTP) in vitro panel using 96 hr exposures to concentrations ranging from 1.0 nM to 10.0 µM. GSK923295A was also tested in vivo against the PPTP acute lymphoblastic leukemia (ALL) and solid tumor xenograft panels using a days 1-3 and 8-10 schedule that was repeated at day 21. The agent was administered via the intraperitoneal (i.p.) route at a daily dose of 125 mg/kg.

Results

The median IC(50) for all PPTP cell lines was 27 nM, with the media

SUBMITTER: Lock RB 

PROVIDER: S-EPMC3163687 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature