Identification of novel MRP3 inhibitors based on computational models and validation using an in vitro membrane vesicle assay.

ABSTRACT:

Introduction

Multidrug resistance-associated protein 3 (MRP3), an efflux transporter on the hepatic basolateral membrane, may function as a compensatory mechanism to prevent the accumulation of anionic substrates (e.g., bile acids) in hepatocytes. Inhibition of MRP3 may disrupt bile acid homeostasis and is one hypothesized risk factor for the development of drug-induced liver injury (DILI). Therefore, identifying potential MRP3 inhibitors could help mitigate the occurrence of DILI.

Methods

Bayesian models were developed using MRP3 transporter inhibition data for 86 structurally diverse drugs. The compounds were split into training and test sets of 57 and 29 compounds, respectively, and six models were generated based on distinct inhibition thresholds and molecular fingerprin

SUBMITTER: Ali I 

PROVIDER: S-EPMC5450158 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature