Pharmacologically Active Metabolites of Currently Marketed Drugs: Potential Resources for New Drug Discovery and Development

Abstract

Biotransformation is the major clearance mechanism of therapeutic agents from the body. Biotransformation is known not only to facilitate the elimination of drugs by changing the molecular structure to more hydrophilic, but also lead to pharmacological inactivation of therapeutic compounds. However, in some cases, the biotransformation of drugs can lead to the generation of pharmacologically active metabolites, responsible for the pharmacological actions. This review provides an update of the kinds of pharmacologically active metabolites and some of their individual pharmacological and pharmacokinetic aspects, and describes their importance as resources for drug discovery and development.

Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950

“…8−10 Sometimes these metabolites guide the development of new and improved drugs. 11 In this Letter, we report the identification, synthesis, and NLRP3 inhibitory activity of the major human microsomal metabolite of the NLRP3 inflammasome inhibitor MCC950 and identify the P450 enzymes, which catalyze its formation.…”

Pharmacologically Active Drug Metabolites: Impact on Drug Discovery and Pharmacotherapy

“…Considerable knowledge has been gained since that time. In fact, active metabolites have been proposed to be potential new material for new drug discovery and development (Kang et al, 2010). Certainly the presence of drugs used clinically that were once metabolites (e.g., fexofenadine) or are prodrugs of these metabolites (fesoterodine) is a testament to this notion (Table 2).…”

A Case of a Schizophrenic Patient with Unusual Pharmacogenetics Profile

“…The optimal ratio of CLO to NOR has not yet been defined, but a ratio of two or more implies that saturation of clozapine metabolism has been reached. 6 It seems that a increase of the CLO/NOR ratio (detected too in PKG86) has potential benefits including both a reduction of such side effects as sedation, weight] gain, metabolic disturbances, and neutropenia, and an increase in efficacy. 7 The above case is reported not only for the unusual PGx but also because it accompanied drugdrug interactions.…”