PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity.

ABSTRACT:

Background and purpose

PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that is currently in phase I clinical development for the treatment of solid tumours. In this study we have characterized the interactions of PM01183 with selected DNA molecules of defined sequence and its in vitro and in vivo cytotoxicity.

Experimental approach

DNA binding characteristics of PM01183 were studied using electrophoretic mobility shift assays, fluorescence-based melting kinetic experiments and computational modelling methods. Its mechanism of action was investigated using flow cytometry, Western blot analysis and fluorescent microscopy. In vitro anti-tumour activity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the in vivo activity utiliz

SUBMITTER: Leal JF 

PROVIDER: S-EPMC2998690 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature