Related Experiment Video
Updated: Feb 28, 2026

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT
Published on: May 2, 2017
Metabolism of KO143, an ABCG2 inhibitor
Ke Liu1, Junjie Zhu1, Yixian Huang1
1Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract:
The ATP-binding cassette sub-family G member 2 (ABCG2) plays an important role in modulating drug disposition and endobiotic homeostasis. KO143 is a potent and relatively selective ABCG2 inhibitor. We found that the metabolic stability of KO143 was very poor in human liver microsomes (HLM). Our further studies illustrated that the tert-butyl ester group in KO143 can be rapidly hydrolyzed and removed by carboxylesterase 1. This metabolic pathway was confirmed as a major pathway of KO143 metabolism in both HLM and mice. K1 is an analog of KO143 without the ester group. We found that the metabolic stability of K1 was significantly improved in HLM when compared to KO143. These data suggest that the ester group in KO143 is the major cause of the poor metabolic stability of KO143. The data from this study can be used to guide the development of KO143 analogs with better metabolic properties.
More Related Videos
Related Concept Videos
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
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...
What is Metabolism?
Drug Metabolism: Phase II Reactions
Drug Biotransformation: Overview
One-Compartment Open Model: Wagner-Nelson and Loo Riegelman Method for ka Estimation
On...

