Sp-6-Phe-cAMPS is a potent, site-selective and membrane-permeable activator of cAMP-dependent protein kinase. Sp-6-Phe-cAMPS does not activate exchange factors directly activated by cAMP and can therefore be used as an Epac negative control. Sp-6-Phe-cAMPS can be used in the study of neurodegenerative diseases.