Covalent drugs haveproved to be successful therapies for various indications, but largely
owing to safety concerns, they are rarely considered when initiating a target-directed drug …

It is generally accepted that there is neither a well-defined nor a consistent link between the
formation of drug−protein adducts and organ toxicity. Because the potential does exist, …

Because of a preconceived notion that eliminating reactive metabolite (RM) formation with
new drug candidates could mitigate the risk of idiosyncratic drug toxicity, the potential for RM …

The primary function of the small intestine is to absorb nutrients and water. This is achieved
by mixing food with digestive enzymes to increase the contact of foodstuffs with the …

The normal metabolism of drugs can generate metabolites that have intrinsic chemical reactivity
towards cellular molecules, and therefore have the potential to alter biological function …

In contrast to the traditional mechanism of drug action that relies on the reversible, noncovalent
interaction of a ligand with its biological target, a targeted covalent inhibitor (TCI) is …

The active forms of all marketed hydroxymethylglutaryl (HMG)-CoA reductase inhibitors
share a common dihydroxy heptanoic or heptenoic acid side chain. In this study, we present …

BACKGROUND In the course of modern drug development, there are four areas in which
issues pertaining to drug metabolites need to be addressed, namely (1) drug metabolites as …

Therapy with the oral antidiabetic agent troglitazone (Rezulin) has been associated with cases
of severe hepatotoxicity and drug-induced liver failure, which led to the recent withdrawal …

Liver damage induced by the antiepileptic drug valproic acid (VPA) is believed to be mediated
by an unsaturated metabolite of the drug, Δ 4 -VPA. In studies of the biological origin of …