Identification of Ligands for the Orphan Nuclear Receptor GCNF

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.