Initial testing (stage 1) of the cyclin dependent kinase inhibitor SCH 727965 (dinaciclib) by the pediatric preclinical testing program.

ABSTRACT:

Background

SCH 727965 is a novel drug in clinical development that potently and selectively inhibits CDK1, CDK2, CDK5, and CDK9. The activity of SCH 727965 was evaluated against the PPTP's in vitro and in vivo panels.

Procedures

SCH 727965 was tested against the PPTP in vitro panel using 96 hours exposure at concentrations ranging from 0.1 nM to 1.0 µM. It was tested against the PPTP in vivo panels at a dose of 40 mg/kg administered intraperitoneally twice weekly for 2 weeks and repeated at Day 21 with a total observation period of 6 weeks.

Results

The median IC(50) value for the cell lines was 7.5 nM, with less than fourfold range between the minimum (3.4 nM) and maximum (11.2 nM) IC(50) values. SCH 727965 demonstrated an activity pattern consistent with cytotoxicity

SUBMITTER: Gorlick R 

PROVIDER: S-EPMC3349821 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature