Effects of the aldehyde dehydrogenase inhibitor disulfiram on the plasma pharmacokinetics metabolism and toxicity of benzaldehyde dimethane sulfonate (NSC281612 DMS612 BEN) in mice

摘要

PurposeBenzaldehyde dimethane sulfonate (DMS612, NSC281612, BEN) is an alkylator with activity against renal cell carcinoma, currently in phase I trials. In blood, BEN is rapidly metabolized into its highly reactive carboxylic acid (BA), presumably the predominant alkylating species. We hypothesized that BEN is metabolized to BA by aldehyde dehydrogenase (ALDH) and aimed to increase BEN exposure in blood and tissues by inhibiting ALDH with disulfiram thereby shifting BA production from blood to tissues.