Title :

Development and implementation of a cell-based assay to discover agonists of the nuclear receptor REV-ERBα

Author(s) :

Hering, Yuliya [Auteur]
Fraunhofer Institute for Molecular Biology and Applied Ecology [Fraunhofer IME]
Berthier, Alexandre [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Duez, Hélène [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Lefebvre, Philippe [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Deprez, Benoit [Auteur]
Médicaments et molécules pour les systèmes vivants - U 1177 [M2SV]
Gribbon, Philip [Auteur]
Fraunhofer Institute for Systems and Innovation Research [Fraunhofer ISI ]
Wolf, Markus [Auteur]
Fraunhofer Institute for Systems and Innovation Research [Fraunhofer ISI ]
Reinshagen, Jeanette [Auteur]
Fraunhofer Institute for Systems and Innovation Research [Fraunhofer ISI ]
Halley, Francoise [Auteur]
Fraunhofer Institute for Systems and Innovation Research [Fraunhofer ISI ]
Hannemann, Juliane [Auteur]
Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] [UKE]
Böger, Rainer [Auteur]
Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] [UKE]
Staels, Bart [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Gul, Sheraz [Auteur]
Fraunhofer Institute for Translational Medicine and Pharmacology [ITMP]

Journal title :

Journal of Biological Methods

Pages :

e94

Publisher :

POL scientific

Publication date :

2018-07-02

HAL domain(s) :

Sciences du Vivant [q-bio]/Sciences pharmaceutiques

English abstract : [en]

The nuclear receptors are transcription factors involved in the regulation of a variety of physiological processes whose activity can be modulated by binding to relevant small molecule ligands. Their dysfunction has been ...
Show more >The nuclear receptors are transcription factors involved in the regulation of a variety of physiological processes whose activity can be modulated by binding to relevant small molecule ligands. Their dysfunction has been shown to play a role in disease states such as diabetes, cancer, inflammatory diseases, and hormonal resistance ailments, which makes them interesting targets for drug discovery. The nuclear receptor REV-ERBα is involved in regulating the circadian rhythm and metabolism. Its natural ligand is heme and there is significant interest in identifying novel synthetic modulators to serve as tools to characterize its function and to serve as drugs in treating metabolic disorders. To do so, we established a mammalian cell-based two-hybrid assay system capable of measuring the interaction between REV-ERBα and its co-repressor, nuclear co-repressor 1. This assay was validated to industry standard criteria and was used to screen a subset of the LOPAC®1280 library and 29568 compounds from a diverse compound library. Profiling of the primary hits in a panel of counter and selectivity assays confirmed that REV-ERBα activity can be modulated pharmacologically and chemical scaffolds have been identified for optimization.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL