The decline in approval of new drugs during the past decade has led to a close analysis of
the drug discovery process. One of the main reasons for attrition is preclinical toxicity …

Clozapine is known to cause hepatotoxicity in a small percentage of patients. Oxidative
bioactivation to reactive intermediates by hepatic cytochrome P450s (P450s) has be …

Exposure to cocaine results in the depletion of hepatocellular glutathione and
macromolecular protein binding in humans. Such cocaine-induced responses have …

The cannabinoid type 1 receptor (CB1r) antagonist rimonabant was approved in 2006 for
the treatment of obesity but was withdrawn in 2008 due to serious drug-related psychiatric …

The carboxylic acid NSAID fenclozic acid exhibited an excellent preclinical safety profile and
promising clinical efficacy, yet was withdrawn from clinical development in 1971 due to …

The current study examined the bioactivation potential of ghrelin receptor inverse agonists, 1-
{2-[2-chloro-4-(2 H-1, 2, 3-triazol-2-yl) benzyl]-2, 7-diazaspiro [3.5] nonan-7-yl}-2-(imidazo [2 …

In the liver microsome cyanide (CN)-trapping assays, piperazine-containing compounds
formed significant N-methyl piperazine CN adducts. Two pathways for the N-methyl …

This micro‐review describes hot topics and new trends in isotope science discussed at the
11th International Isotope Symposium on the Synthesis and Applications of Isotopes and …

Approaches to the Detection of Adducts formed via the Covalent Binding of Reactive
Metabolites to Proteins A thesis submitted to The University of Manchester for the degree of …