Identification of Ligands for the Orphan Nuclear Receptor GCNF

• DOI: 10.1007/s00044-004-0027-5
• Publication Date: 2005-08-08T11:46:38Z
• Authors: Rogier Buijsman; Anja Garritsen; Jan Gossen; Jan Klomp; Cor Kuil; Paula van Noort; Rachel van Rijn; Gerben Rovers; Willem Schoonen; Jan Gerard Sterre...; Thijs Stock; Geert Verdonk; Arie Vesser; Stan van Boeckel; Rein Dijkema; Pedro Hermkens
• Keywords: 0303 health sciences; 03 medical and health sciences

HTS has been executed with a luciferase reporter assay in CHO cells stably expressing an ERa/GCNF chimer. Confirmed hits could be optimized some 10 to 100 fold. Partial agonists identified during the hit optimization process behaved as antagonists in a competition based variant of the reporter assay. The latter assay format was also used to identify some full antagonists by HTS. GCNF binding of agonists and antagonists was confirmed by GCNF/cofactor interactions studies in solution.