PreMetabo: An in silico phase I and II drug metabolism prediction platform.

This study aimed to develop a drug metabolism prediction platform using knowledge-based prediction models. Site of Metabolism (SOM) prediction models for four cytochrome P450 (CYP) subtypes were developed along with uridine 5'-diphosphoglucuronosyltransferase (UGT) and sulfotransferase (SULT) substrate classification models. The SOM substrate for a certain CYP was determined using the sum of the activation energy required for the reaction at the reaction site of the substrate and the binding energy of the substrate to the CYP enzyme.

Inhibition of Cytochrome P450 Activities by Extract and Its Prenylated Flavonoids in Human Liver Microsomes.

possesses several pharmacological properties and has been widely used for the treatment of diarrhea, inflammation, abscess, dysentery, and fever in East Asian countries. is a major source of prenylated flavonoids, such as sophoraflavone and kushenol. In this study, we examined the effects of extract and its prenylated flavonoids on cytochrome P450 (CYP) isoform activity in human liver microsomes.

Identification and characterization of amiodarone metabolites in rats using UPLC-ESI-QTOFMS-based untargeted metabolomics approach.

Amiodarone is a class III anti-arrhythmic benzofuran derivative extensively utilized in treatment of life-threatening ventricular and supraventricular arrhythmias. However, amiodarone also produces adverse side effects including liver injury due to its metabolites rather than parent drug. The purpose of the present study was to identify metabolites of amiodarone in the plasma and urine of rats administered the drug by using an untargeted metabolomics approach.

Regioselective C-H hydroxylation of omeprazole sulfide by Bacillus megaterium CYP102A1 to produce a human metabolite.

Objectives: To find a simple enzymatic strategy for the efficient synthesis of the expensive 5'-hydroxyomeprazole sulfide, a recently identified minor human metabolite, from omeprazole sulfide, which is an inexpensive substrate.

Results: The practical synthetic strategy for the 5'-OH omeprazole sulfide was accomplished with a set of highly active CYP102A1 mutants, which were obtained by blue colony screening from CYP102A1 libraries with a high conversion yield. The mutant and even the wild-type enzyme of CYP102A1 catalyzed the high regioselective (98 %) C-H hydroxylation of omeprazole sulfide to 5'-OH omeprazole sulfide with a high conversion yield (85-90 %).