Ka : 0.05 and 0.11 μM for PKA and PKG, respectively
8-CPT-Cyclic AMP is a lipophilic activator of the cyclic-AMP- and cyclic-GMP-dependent protein kinases, PKA and PKG.
The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response element (CRE)-dependent gene transcription was compared with that of cAMP-dependent protein kinases (cAKs).
In vitro: A previous study found that 8-CPT-Cyclic AMP was a potent activator of cAMP-PK and cyclic-GMP-dependent protein kinase (cGMP-PK) both as purified enzymes and in platelet membranes. 8-CPT-Cyclic AMP was hydrolysed to a significant extent by the Ca2+/calmodulin-dependent phosphodiesterase and by the cGMP-inhibited phosphodiesterase. Moreover, Sp-5,6- DCl-cBiMPS was also more effective than 8-CPT-Cyclic AMP in inducing quantitative phosphorylation of vasodilator-stimulated phosphoprotein in intact platelets [1]. Another study indicated that 8-CPT-Cyclic AMP was a potent inhibitor of the cyclic GMP-specific phosphodiesterase (PDE VA). Indeed, 8-CPT-Cyclic AMP could inhibit PDE VA with a potency similar to that of zaprinast. In addition, 8-CPT-Cyclic AMP was metabolized by PDE VA at a rate half that of cyclic GMP. The cyclic GMP-inhibited phosphodiesterase and the cyclic AMP-specific phosphodiesterase could be inhibited by 8-CPT-Cyclic AMP as well [2].
In vivo: Up to now, there is no animal in vivo data reported.
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Sandberg, M. ,Butt, E.,Nolte, C., et al. Characterization of Sp-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole-3',5'-monophosphorothioate (Sp-5,6-DCl-cBiMPS) as a potent and specific activator of cyclic-AMP-dependent protein kinase in cell extracts and intact cells. Biochemistry Journal 279, 521-527 (1991).
[2] Connolly, B. J.,Willits, P.B.,Warrington, B.H., et al. 8-(4-chlorophenyl)thio-cyclic AMP is a potent inhibitor of the cyclic GMP-specific phosphodiesterase (PDE VA). Biochemical Pharmacology 44(12), 2303-2306 (1992).
