Inhibitor SourceBook™ Second Edition

Calbiochem • Inhibitor SourceBook
Phosphorylation/Dephosphorylation
Protein Kinase G (PKG; cGMP-Dependent Protein Kinase) Inhibitors
cGMP produces its effects by interacting with
intracellular receptor proteins. A primary action of
elevated cGMP levels is the stimulation of cGMPdependent
protein kinase (PKG), which catalyzes the
phosphorylation of a number of physiologically relevant
proteins involved in contractile activity of smooth
muscle cells. The mammalian PKG family consists of
PKGIa and Ib, splice forms derived from one gene, and
PKGII, encoded by a second gene. They are ubiquitous
effector enzymes that regulate a variety of physiological
processes in response to nitric oxide and natriuretic
agonists. Cells of the cardiovascular system, such as
fibroblasts and certain types of endothelial cells, contain
PKGI. Smooth muscle cells are rich in PKGIa and Ib,
platelets and T lymphocytes contain PKGIb, and cardiac
myocytes contain PKGIa. It is important to note that
PKGs are lost in many primary cell types upon passaging
in cell culture and may not be detected in many cell
lines. Studies have shown that cultured vascular smooth
muscle cells (VSMCs) may stop expressing PKG and
acquire a non-contractile phenotype. The restoration
of PKG expression can result in the cells acquiring
a more contractile phenotype. This is an important
observation because several vascular disorders result
from accumulation of noncontractile VSMC in the
vessel wall. In endothelial cells PKGI phosphorylates
and activates eNOS, which reduces its Ca 2+ -dependence.
Also, in endothelial cells, PKGI and PKGII are known
to phosphorylate 6-pyruvoyltetrahydropterin synthase
to produce tetrahydrobiopterin, a required cofactor for
eNOS activation.
References:
Protein Kinase G (PKG; cGMP-Dependent Protein Kinase) Inhibitors
Feil, R., et al. 2005, Rev. Neurosci. 16, 23.
Munzel, T., et al. 2003. Circulation 108, 2 72.
Browning, D.D., et al. 200 . J. Biol. Chem. 276, 3039.
Wang, X., and Robinson, P.J. 997. J. Neurochem. 68, 443.
Lincoln, T.M., et al. 200 . J. Appl. Physiol. 91, 42 .
Product Cat. No. Comments Size Price
A3, Hydrochloride 100122 [N-(2-Aminoethyl)-5-chloronaphthalene-1-sulfonamide, HCl]
A shorter alkyl chain derivative of W-7 (Cat. No. 68 629) that inhibits PKG (K i = 3.8 mM),
casein kinase I (K i = 80 mM), casein kinase II (K i = 5. mM), MLCK (K i = 7.4 mM), PKA
(K i = 4.3 mM), and PKC (K i = 47 mM).
Drosophila
Antennapedia Homeo-
Domain (43-58)
Guanosine 3´,5´-cyclic
Monophosphorothioate,
Rp-Isomer,
Triethylammonium Salt
Guanosine 3´,5´-cyclic
Monophosphorothioate,
8-Bromo-, Rp-Isomer,
Sodium Salt
Guanosine 3´,5´-cyclic
Monophosphorothioate,
8-(4-Choloro-
phenylthio)-, Rp-
Isomer,
Triethylammonium Salt
Guanosine 3´,5´-cyclic
Monophosphorothioate,
b-Phenyl- , N 2 -etheno-
8-bromo-, Rp-Isomer,
Sodium Salt
More online... www.calbiochem.com/inhibitors/PKG
287895 (DT-5; RQIKIWFQNRRMKWKK)
The membrane translocation signal sequence from Drosophila Antennapedia homeodomain
(43-58) that inhibits PKGIa (K i = 970 nM). Does not exhibit significant inhibition
against PKA (K i = 07 mM).
370666 (Rp-cGMPS, TEA)
A competitive inhibitor of PKGIa that blocks PKG and PKA activation (K i = 20 mM).
Exhibits low cell permeability.
370674 (Rp-8-Br-cGMPS, Na)
A potent, cell-permeable, metabolically stable inhibitor of PKG. Significantly more
lipophilic and membrane-permeable than cGMP or Rp-cGMPS. Resistant to mammalian
cyclic nucleotide-dependent phosphodiesterases.
370677 (Rp-8-pCPT-cGMPS, TEA)
A potent, cell-permeable inhibitor of PKG Ia, Ib, and type II. A combination of the protein
kinase inhibitor Rp-cGMPS and the widely used cGMP analog, 8-pCPT-cGMP. Significantly
more lipophilic and membrane-permeant than Rp-cGMPS and Rp-8-Br-cGMPS. Resistant
to hydrolysis by mammalian cyclic nucleotide dependent phosphodiesterases.
370679 (Rp-8-Br-PET-cGMPS, Na)
A metabolically stable, competitive inhibitor of PKGIa and Ib (K i = 30 nM).
Also reported to block the activation of purified PKA type II (K i = 0 mM).
More lipophilic and cell-permeable than Rp-8-pCPT-cGMPS (Cat. No. 370677).
0 mg $90
mg $90
5 mmol $348
5 mmol $430
mmol $2 5
mmol $ 4
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