Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

A phenotypic high throughput screening assay for the identification of pharmacoperones for the gonadotropin releasing hormone receptor

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Conn, P. M.
  • Smith, E.
  • Spicer, Timothy
  • Chase, P.
  • Scampavia, Louis
  • Janovick, J. A.

publication date

  • May 2014

journal

  • Assay and Drug Development Technologies  Journal

abstract

  • We describe a phenotypic high throughput screening (HTS) calcium flux assay designed to identify pharmacoperones for the gonadotropin releasing hormone receptor (GnRHR). Pharmacoperones are target-specific, small molecules that diffuse into cells, rescue misfolded protein mutants, and restore them to function. Rescue is based on correcting the trafficking of mutants that would otherwise be retained in the endoplasmic reticulum and unable to function correctly. This approach identifies drugs with a significant degree of novelty, relying on cellular mechanisms that are not currently exploited. Development of such assays is important, since the extensive use of agonist/antagonist screens alone means that useful chemical structures may be present in existing libraries but have not been previously identified using existing methods. Our assay utilizes cell lines stably expressing a GnRHR mutant under the control of a tetracycline (OFF) transactivator. This allows us to quantitate the level of functional and properly trafficked G protein coupled receptors present in each test well. Furthermore, since we are able to turn receptor expression on and off, we can rapidly eliminate the majority of false positives from our screening results. Our data show that this approach is likely to be successful in identifying hits from large chemical libraries.

subject areas

  • Calcium
  • Endoplasmic Reticulum
  • HeLa Cells
  • High-Throughput Screening Assays
  • Humans
  • Mutation
  • Receptors, G-Protein-Coupled
  • Receptors, LHRH
  • Signal Transduction
  • Small Molecule Libraries
scroll to property group menus

Identity

PubMed Central ID

  • PMC4025569

International Standard Serial Number (ISSN)

  • 1540-658X

Digital Object Identifier (DOI)

  • 10.1089/adt.2014.576

PubMed ID

  • 24831790
scroll to property group menus

Additional Document Info

start page

  • 238

end page

  • 246

volume

  • 12

issue

  • 4

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support