A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs

Yong Jun Kwon, Weontae Lee, Auguste Genovesio, Neil Emans

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

G-protein-coupled receptors (GPCRs) are pivotal in cellular responses to the environment and are common drug targets. Identification of selective small molecules acting on single GPCRs is complicated by the shared machinery coupling signal transduction to physiology. Here, we demonstrate a high-content screen using a panel of GPCR assays to identify receptor selective molecules acting within the kinase/phosphatase inhibitor family. A collection of 88 kinase and phosphatase inhibitors was screened against seven agonist-induced GPCR internalization cell models as well as transferrin uptake in human embryonic kidney cells. Molecules acting on a single receptor were identified through excluding pan-specific compounds affecting housekeeping endocytosis or disrupting internalization of multiple receptors. We identified compounds acting on a sole GPCR from activities in a broad range of chemical structures that could not be easily sorted by conventional means. Selective analysis can therefore rapidly select compounds selectively affecting GPCR activity with specificity to one receptor class through high-content screening.

Original languageEnglish
Pages (from-to)379-385
Number of pages7
JournalJournal of Biomolecular Screening
Volume17
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

Fingerprint

G-Protein-Coupled Receptors
Molecules
Phosphoric Monoester Hydrolases
Phosphotransferases
Housekeeping
Signal transduction
Physiology
Transferrin
Endocytosis
Machinery
Assays
Signal Transduction
Screening
Kidney
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

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A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs. / Kwon, Yong Jun; Lee, Weontae; Genovesio, Auguste; Emans, Neil.

In: Journal of Biomolecular Screening, Vol. 17, No. 3, 01.03.2012, p. 379-385.

Research output: Contribution to journalArticle

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