Characterization of the metabolism of benzaldehyde dimethane sulfonate (NSC 281612, DMS612).

ABSTRACT:

Introduction

Benzaldehyde dimethane sulfonate (BEN, DMS612, NSC281612) is a bifunctional alkylating agent currently in clinical trials. We previously characterized the degradation products of BEN in plasma and blood. The conversion of BEN to its carboxylic acid analogue (BA) in whole blood, but not plasma, suggests that an enzyme in RBCs may be responsible for this conversion. BEN conversion to BA was observed in renal carcinoma cells and appeared to correlate with IC₅₀. To better understand the pharmacology of BEN, we aimed to evaluate the metabolism and enzymes potentially responsible for the conversion of BEN to BA.

Methods

Human red blood cells (RBC) were used to characterize kinetics and susceptibility to enzyme-specific inhibitors. Recombinant enzymes were used to conf

SUBMITTER: Parise RA 

PROVIDER: S-EPMC4545378 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature