LIVE CELL PROCEDURES TO IDENTIFY COMPOUNDS MODULATING INTRACELLULAR DISTRIBUTION OF PHOSPHODIESTERASE (PDE) ENZYMES

摘要

An alternative therapeutic approach for PDE4 inhibition is disclosed. PDE4 dislocators, will remove the PDE4 away from the native location in the cell and thereby increase the concentration of cAMP in this location. By dislocating the PDE4, and thereby not acting directly on the catalytic, among phosphodiesterase inhibitors, well conserved site, the compound will act e.g. at the binding domain of the PDE4, thereby providing isoform-specific 'inhibitors' of PDE4. The dislocation of PDE4s are visualised with fusions to GFP. The native location is induced by treatment with Rolipram.