KT5720

Description

Protein kinase A (PKA) regulates multiple signal transduction events via protein phosphorylation and is integral to all cellular responses involving the cyclic AMP second messenger system. KT 5720 is one of a family of compounds synthesized by the fungus Nocardiopsis sp. It blocks PKA signaling through competitive inhibition of ATP with a K_i value of 60 nM. Reported IC₅₀ values vary widely depending upon ATP concentration tested and can range from 56 nM (low ATP) to 3 μM (physiologic ATP). Non-specific effects of KT 5720 include inhibition of phosphorylase kinase, PDK1, MEK, MSK1, PKBα, and GSK3β at concentrations as effective as or more potent than that for inhibition of PKA.

Chemical Properties

White solid

Uses

KT 5720 is a potent, specific and cell-permeable inhibitor of PKA.

Definition

ChEBI: 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 hexyl (3S)-3-hydroxy-2-methyltetrahydrofuran-3- arboxylate (the 2R,3S,5S 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 1,5-dihydro-2H-pyrrol- -one.

Biological Activity

Potent, selective inhibitor of protein kinase A (K i = 60 nM). Has no effect on PKG or PKC (K i > 2 μ M). Reversibly arrests human skin fibroblasts in the G 1 phase. Also available as part of the Mixed Kinase Inhibitor Tocriset™ and PKA Tocriset™ .

Biochem/physiol Actions

Cell permeable: yes

storage

-20°C (desiccate)

References

1) Kase et al. (1987), K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases; Biochem. Biophys. Res. Commun., 142 436 2) Cabell et al. (1993), Effects of selective inhibition of protein kinase C, cyclic AMP-dependent protein kinase, and Ca(2+)-calmodulin-dependent protein kinase on neurite development in cultured rat hippocampal neurons; Int. J. Dev. Neurosci., 11 357