Related Experiment Video
Updated: Apr 8, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Novel Bioactivation Pathway of Benzbromarone Mediated by Cytochrome P450
Yumina Kitagawara1, Tomoyuki Ohe2, Kumiko Tachibana1
1Faculty of Pharmacy, Keio University, Tokyo, Japan (Y.K., T.O., K.T., T.M.); Department of Chemistry, Nippon Medical School, Tokyo, Japan (S.N.).
Abstract:
Benzbromarone (BBR) is a hepatotoxic drug, but the detailed mechanism of its toxicity remains unknown. We identified 2,6-dibromohydroquinone (DBH) and mono-debrominated catechol (2-ethyl-3-(3-bromo-4,5-dihydroxybenzoyl)benzofuran; CAT) as novel metabolites of BBR in rat and human liver microsomal systems by comparison with chemically synthesized authentic compounds, and we also elucidated that DBH is formed by cytochrome P450 2C9 and that CAT is formed mainly by CYP1A1, 2D6, 2E1, and 3A4. Furthermore, CAT, DBH, and the oxidized form of DBH are highly cytotoxic in HepG2 compared with BBR. Taken together, our data demonstrate that DBH, a novel reactive metabolite, may be relevant to BBR-induced hepatotoxicity.
More Related Videos
10:44Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
09:33Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Related Concept Videos
Bioactivation and Tissue Toxicity
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Drug Metabolism: Phase I Reactions
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Drug Biotransformation: Overview
Drug Biotransformation: Overview