Description
STO-609 (1173022-21-3) is a selective inhibitor of Ca2+-calmodulin-dependent protein kinase kinase (Ki = 80 and 15 ng/ml for inhibition of CaM-KKα and CaM-KKβ respectively).1 Binds to the? ATP-binding site.2 Displays > 80-fold selectivity over CaMK1, CaMK2, CaMK4, MLCK, PKC, PKA and p42 MAPK. Important tool for probing distinct CaMK pathways in LTP.3 Reduces starvation-induced autophagosomal membrane formation.4 Reverses age-associated decline in bone mass.5 Stimulates osteoblast formation, inhibits osteoclast differentiation.6
Uses
STO-609 is a cell-permeable inhibitor of calcium/calmodulin-dependent kinase kinases (CaMKK) isoforms CaMKKα and CaMKKβ. It is used to evaluate the action of CaMKK isoforms both in vitro and in cells.
General Description
STO-609 reduces tumorigenicity of liver cancer cells
in vivo. TO-609 reduces the activation of AMP (adenosine monophosphate)-activated protein kinase (AMPK) by ionomycin in a dose dependant manner.
Biochem/physiol Actions
Selective Ca2+/Calmodulin-dependent protein kinase kinase (CaM-KK) antagonist. Inhibits CamKKa and CaMKKb with Ki = 80 and 15 ng/mL, respectively. Does not inhibit downstream CaM kinases (CaMKI and CaMKIV).
storage
Room temperature (desiccate)
References
1) Tokumitsu?et al. (2002), STO-609, a Specific Inhibitor of the Ca2+/Calmodulin-dependent Protein Kinase Kinase;?J. Biol. Chem. 277 15813
2) Tokumitsu?et al. (2003) A single amino acid difference between alpha and beta Ca2+/calmodulin-dependent protein kinase kinase dictates sensitivity to the specific inhibitor, STO-609;?J. Biol. Chem. 278 10908
3) Redondo et al. (2010) Synaptic tagging and capture: differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation;?J. Neurosci. 30 4981
4) Pfisterer et al. (2011) Ca+2/calmodulin –dependent kinase (CaMK) signaling via CaMKI and AMP-activated protein kinase contributes to the regulation of WIPI-1 ar the onset of autophagy; Mol. Pharmacol. 80 1066
5) Pritchard et al. (2015) Inhibition of CaMKK2 reverses age-associated decline in bone mass; Bone, 75 120
6)Cary?et al. (2013) Inhibition of Ca+2/Calmodulin-dependent protein kinase kinase 2 stimulates osteoblast formation and inhibits osteoclast differentiation;?J. Bone Miner. Res. 28 1599
7) Matsukawa et al. (2017) Upregulation of skeletal muscle PGC-1α through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance; Sci. Rep., 7 44799
