Effects of the kinase inhibitor sorafenib on heart, muscle, liver and plasma metabolism in vivo using non-targeted metabolomics analysis.

ABSTRACT:

Background and purpose

The human kinome consists of roughly 500 kinases, including 150 that have been proposed as therapeutic targets. Protein kinases regulate an array of signalling pathways that control metabolism, cell cycle progression, cell death, differentiation and survival. It is not surprising, then, that new kinase inhibitors developed to treat cancer, including sorafenib, also exhibit cardiotoxicity. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical roles of protein kinases in cardiac metabolism.

Experimental approach

FVB/N mice (10 per group) were challenged with sorafenib or vehicle control daily for 2 weeks. Echocardiographic assessment of the heart identified systolic d

SUBMITTER: Jensen BC 

PROVIDER: S-EPMC5727336 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature