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A new approach for insulin receptor ligand screening

Reference

84900-01

Keywords

Insulin

Patents status

French patent application FR0105737 filed on April 27th, 2001 entitled “Méthode de détection de composés activateurs ou inhibiteurs des récepteurs de la famille du récepteur de l’insuline au moyen d’un récepteur chimère isolé” and granted on June 13, 2003.
WO 02 088752 published on November 7, 2002.

Inventors

Tarik ISSAD
Nicolas BOUTE
Karine PERNET

commercial status

Research agreement, exclusive or non exclusive licences

Laboratory

Institut Cochin, a CNRS, INSERM and Université Paris 5 laboratory (UMR 8104) in Paris, France.

Description

TECHNICAL DESCRIPTION

This invention involves a procedure based on Bioluminescence Resonance Energy Transfer (BRET) to monitor the activation state of the insulin receptor in vitro. A human insulin receptor with one -beta-subunit fused to Renilla luciferase (Rluc) and the other -beta-subunit fused to the Enhanced Yellow Fluorescent Protein (EYFP) has been developed. The conformational change induced by insulin and other ligands can be detected as an energy transfer (BRET signal) between Rluc and EYFP. BRET signal parallels the effects of the ligands on receptor tyrosine kinase activity. Purified chimeric insulin receptors can be prepared on a large scale and stored at -80 °C for subsequent use. This preparation can be distributed automatically in 96 well microplates and the effect of molecules on insulin receptor activity can be measured in a few minutes with the BRET methodology.

INDUSTRIAL APPLICATION

High-throughput screening test to identify novel molecules with insulin-like activities (Boute et al., 2001, Mol. Pharm. 60, 640-645; Boute et al. TiPS, 23 351-354, 2002).
This assay will be a valuable tool:
– for the discovery of molecules with therapeutic properties, particularly in the field of diabetes and obesity,
– for the discovery of inhibitors with therapeutic properties in the field of IGF1-receptor associated cancers.

For further information, please contact us (Ref 84900-01)

 


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