Identification of a new class of prostaglandin transporter inhibitors and characterization of their biological effects on prostaglandin E2 transport

Yuling Chi, Sonya M. Khersonsky, Young Tae Chang, Victor L. Schuster

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Prostaglandins (PGs) are involved in several major signaling pathways. Their effects are terminated when they are transported across cell membranes and oxidized intracellularly. The transport step of PG metabolism is carried out by the prostaglandin transporter (PGT). Inhibition of PGT would therefore be expected to change local or circulating concentrations of prostaglandins, and thus their biological effects. To develop PGT-specific inhibitors with high affinity, we designed a library of triazine compounds and screened 1842 small molecules by using Madin-Darby canine kidney cells stably expressing rat PGT. We found several effective PGT inhibitors. Among them, the most potent inhibitor had a Ki of 3.7 ± 0.2 μM. These inhibitors allowed us to isolate the efflux process of PGE2 and to demonstrate that PGT does not transport PGE2 outwardly under physiological conditions.

Original languageEnglish (US)
Pages (from-to)1346-1350
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume316
Issue number3
DOIs
StatePublished - Mar 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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