Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions As Potential Mechanisms of Drug-Drug Interactions

Overview

Journal Drug Metab Dispos

Specialty Pharmacology

Date 2018 Mar 9

PMID 29514827

Citations 30

Authors

Rebecca R Crawford

Praveen K Potukuchi

Erin G Schuetz

John D Schuetz

Affiliations

Soon will be listed here.

Abstract

ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many therapeutic compounds, including anticancer drugs. The ABC transporters are also recognized as important contributors to pharmacokinetics, especially in drug-drug interactions and adverse drug effects. Drugs and xenobiotics, as well as pathologic conditions, can influence the transcription of ABC transporters, or modify their activity or intracellular localization. Kinases can affect the aforementioned processes for ABC transporters as do protein interactions. In this review, we focus on the ABC transporters ABCB1, ABCB11, ABCC1, ABCC4, and ABCG2 and illustrate how kinases and protein-protein interactions affect these transporters. The clinical relevance of these factors is currently unknown; however, these examples suggest that our understanding of drug-drug interactions will benefit from further knowledge of how kinases and protein-protein interactions affect ABC transporters.

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