Regulation of OATP1B1 Function by Tyrosine Kinase-mediated Phosphorylation.

ABSTRACT:

Purpose

OATP1B1 (SLCO1B1) is the most abundant and pharmacologically relevant uptake transporter in the liver and a key mediator of xenobiotic clearance. However, the regulatory mechanisms that determine OATP1B1 activity remain uncertain, and as a result, unexpected drug-drug interactions involving OATP1B1 substrates continue to be reported, including several involving tyrosine kinase inhibitors (TKI).

Experimental design

OATP1B1-mediated activity in overexpressing HEK293 cells and hepatocytes was assessed in the presence of FDA-approved TKIs, while rosuvastatin pharmacokinetics in the presence of an OATP1B1 inhibiting TKI were measured in vivo. Tyrosine phosphorylation of OATP1B1 was determined by LC/MS-MS-based proteomics and transport function was measured followin

SUBMITTER: Hayden ER 

PROVIDER: S-EPMC8358987 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature