METHOD OF IDENTIFYING COMPOUNDS THAT ALTER BAG-1 MEDIATED DOWN-REGULATION OF GLUCOCORTICOID-RECEPTOR TRANSACTIVATION

摘要

The present invention relates to new methods of identifying compounds that inhibit or reduce bag-1 mediated downregulation of glucocorticoid-receptor (GR) transactivation. These methods rely on the surprising findings, that first, a (poly)peptide comprising the motif X-Lys-Lys-Lys-Y-Arg-Arg-Arg also present is the cochaperone bag-1 is sufficient for DNA binding of this cochaperone and, second, this motif but not the E2X4 domain of bag-1 is required for inhibition or reduction of FR transactivation. The present invention also relates to methods of refining the compounds identified with the above method as well as to methods of producing pharmaceutical compositions wherein compounds identified or compounds refined by the above-recited methods of the invention are formulated with a pharmaceutically acceptable carrier or diluent.