Description
KT5823 (126643-37-6) is a selective protein kinase G inhibitor (K>i =0.23, 4 and >10 μM for PKG, PKC and PKA respectively.1Arrests human skin fibroblast cell cycle after the G0/G1 boundary.2 KT5823 abolishes the cGMP-induced relaxation in smooth muscle cells (IC50=60 nM).3Cell permeable.
Chemical Properties
Yellow powder
Uses
KT 5823 is a protein kinase inhibitor shown to increase TSH-induced NIS expression, and thus iodide uptake, in thyroid cells.
Uses
KT 5823 has been used as cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor in cortical cultures, cortical neurons and in mouse brain capillary endothelial cells.
Definition
ChEBI: KT 5823 is an organic heterooctacyclic compound that is 1H,1'H-2,2'-biindole in which the nitrogens have undergone formal oxidative coupling to positions 2 and 5 of methyl (3R)-3-methoxy-2-methyltetrahydrofuran-3-carboxylate (the 2S,3R,5R product), and in which the 3 and 3' positions of the biindole moiety have also undergone formal oxidative coupling to positions 3 and 4 of 1-methyl-1,5-dihydro-2H-pyrrol-2-one. It has a role as an EC 2.7.11.12 (cGMP-dependent protein kinase) inhibitor. It is a gamma-lactam, an organic heterooctacyclic compound, a methyl ester, a hemiaminal and an indolocarbazole.
General Description
Highly specific cell-permeable, reversible, and ATP-competitive inhibitor of protein kinase G (K
i = 234 nM). Inhibits protein kinase C (K
i = 4.0 μM) and protein kinase A (K
i >10.0 μM) at higher concentrations.
Biological Activity
Selective inhibitor of protein kinase G (K i values are 0.23, 4 and > 10 μ M for inhibition of PKG, PKC and PKA respectively). Inhibits SNP-stimulated PKG activity with an IC 50 of 60 nM in dispersed smooth muscle cells and has little effect on PKA activity at concentrations of up to 10 μ M. Also available as part of the Mixed Kinase Inhibitor Tocriset™ .
Biochem/physiol Actions
Cell permeable: yes
storage
-20°C (desiccate)
References
[1] HIROSHI KASE. K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases[J]. Biochemical and biophysical research communications, 1987, 142 2: Pages 436-440. DOI:
10.1016/0006-291x(87)90293-2[2] D M GADBOIS. Multiple kinase arrest points in the G1 phase of nontransformed mammalian cells are absent in transformed cells.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1992, 89 18: 8626-8630. DOI:
10.1073/pnas.89.18.8626[3] K S MURTHY G M M. Interaction of cA-kinase and cG-kinase in mediating relaxation of dispersed smooth muscle cells.[J]. American Journal of Physiology, 1995, 268 1 Pt 1: C171-80. DOI:
10.1152/ajpcell.1995.268.1.c171
