IC50: 18.3 and 0.16 μM for cGK Iα and cGK II, respectively.
Rp-8-pCPT-Cyclic GMPS is a GMP-dependent protein kinases (cGKs) inhibitor.
Appreciation of cGMP as a distinct intracellular second messenger is reported to be closely followed by an intensive search for effector proteins in various organisms. A cGMP-dependent protein kinase (cGK) has been found in arthropods resulting in the eventual isolation of cGK from mammalian tissues.
In vitro: Previous study found that Rp-8-pCPT-Cyclic GMPS could selectively inhibit cGK activity in intact human platelets. The IC50 value of Rp-8-pCPT-Cyclic GMPS for cGK II was 114-fold lower than that for cGK Iα in the presence of 1 mM cGMP. In the presence of 10 mM cGMP, the IC50 values of Rp-8-pCPT-Cyclic GMPS for cGK Iα and cGK II increased 3- and 11-fold, respectively. In addition, millimolar concentrations of Rp-8-pCPT-Cyclic GMPS could fully activate both enzymes, a phenomenon that was observed previously for cGK II. Because substitutions at the 8-position of the guanine ring are poorly tolerated by cGK Ib, these results suggested that the Rp-isomer of 8-pCPT-cGMPS might be a selective activator or inhibitor, respectively, of cGK II compared to the cGK I isoforms [1].
In vivo: Up to now, there is no animal in vivo study reported.
Clinical trial: So far, no clinical study has been conducted.
Reference:
[1] Gamm, D. M.,Francis, S.H.,Angelotti, T.P., et al. The type II isoform of cGMP-dependent protein kinase is dimeric and possesses regulatory and catalytic properties distinct from the type I isoforms. The Journal of Biological Chemisty 270(45), 27380-27388 (1995).