Testing of the Akt/PKB inhibitor MK-2206 by the Pediatric Preclinical Testing Program.

ABSTRACT:

Background

MK-2206 is a small molecule allosteric inhibitor of Akt/PKB that is undergoing clinical trials for treatment of cancer.

Procedures

MK-2206 was tested against the PPTP in vitro panel using a 96-hour exposure (1.0 nM-10 µM), and in vivo using thrice weekly dosing for a planned 4 weeks at its maximum tolerated dose (MTD) of 180 mg/kg.

Results

In vitro, the median relative IC(50) value for MK-2206 was 2.2 µM. Four cell lines with IC(50) values < 200 nM included two ALL cell lines (COG-LL-317 and RS4;11), an AML cell line with an activating KIT mutation (Kasumi-1), and a Ewing sarcoma cell line (CHLA-10). In vivo, MK-2206 induced significant differences in EFS distribution compared to control in 12 of 29 (41%) of the evaluable solid tumor xenografts and in 2 of

SUBMITTER: Gorlick R 

PROVIDER: S-EPMC3290691 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature