A targeted in vivo SILAC approach for quantification of drug metabolism enzymes: regulation by the constitutive androstane receptor.

ABSTRACT: The modulation of drug metabolism enzyme (DME) expression by therapeutic agents is a central mechanism of drug-drug interaction and should be assessed as early as possible in preclinical drug development. Direct measurement of DME levels is typically achieved by Western blotting, qPCR, or microarray, but these techniques have their limitations; antibody cross-reactivity among highly homologous subfamilies creates ambiguity, while discordance between mRNA and protein expression undermines observations. The aim of this study was to design a simple targeted workflow by combining in vivo SILAC and label-free proteomics approaches for quantification of DMEs in mouse liver, facilitating a rapid and comprehensive evaluation of metabolic potential at the protein level. A total of 197 peptides, rep

SUBMITTER: Macleod AK 

PROVIDER: S-EPMC3923450 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature