Ki: 30 nM
Sp-5,6-dichloro-cBIMPS is a PKA activator.
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP. PKA is also known as cAMP-dependent protein kinase. PKA has several functions in the cell, such as regulation of sugar, glycogen, and lipid metabolism.
In vitro: Sp-5,6-dichloro-cBIMPS was found to be both a potent and specific activator of purified cAMP-PK and of cAMP-PK in platelet membranes, whereas 8-pCPT-cAMP proved to be a potent activator of cAMP-PK and cyclic-GMP-dependent protein kinase both as purified enzymes and in platelet membranes. Moreover, it was found that Sp-5,6-dichloro-cBIMPS was not significantly hydrolysed by three types of cyclic nucleotide phosphodiesterases, whereas 8-pCPT-cAMP was hydrolysed to a significant extent by the Ca2+/calmodulin-dependent phosphodiesterase and by the cGMP-inhibited phosphodiesterase. The apparent lipophilicity of Sp-5,6-dichloro-cBIMPS was higher than that of 8-pCPT-cAMP. Extracellular application of Sp-5,6-dichloro-cBIMPS to intact human platelets could reproduce the pattern of protein phosphorylation that was induced by prostaglandin E1. Additionally, in intact platelets, Sp-5,6-dichloro-cBIMPS was also more effective than 8-pCPT-cAMP in inducing quantitative phosphorylation of vasodilator-stimulated phosphoprotein, a major substrate of cAMP-PK in platelets. As demonstrated by prostaglandin E1, pretreatment of human platelets with Sp-5,6-DCl-cBiMPS Sp-5,6-dichloro-cBIMPS was able to prevent the aggregation induced by thrombin [1].
In vivo: Up to now, there is no animal in vivo data reported.
Clinical trial: So far, no clinical study has been conducted.
Reference:
[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).