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Overview
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Background
STO-609 acetate is a specific inhibitor of the Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), with Ki values of 80 and 15 ng/ml against CaM-KKα and CaM-KKβ isoforms, respectively [1].
CaM-KKα and CaM-KKβ, highly expressed in the brain with the α isoform also expressed in various peripheral tissues such as thymus and spleen in mammals, belongs to Ca2+/calmodulin-dependent protein kinases, which are involved in many cellular responses mediated by an increase in the concentration of intracellular calcium [1].
STO-609 exhibited high selectivity for CaM-KK without significantly affecting the downstream CaM kinases (CaM-KI and -IV), and the IC50 value of STO-609 against CaM-KII was ~ 10 μg/ml. In transfected HeLa cells, STO-609 (0.01 ~ 10 μg/ml) suppressed the Ca2+-induced activation of CaM-KIV in a dose-dependent manner. In addition, in SH-SY5Y neuroblastoma cells, STO-609 at a concentration of 1 μg/ml significantly reduced the endogenous activity of CaM-KK [1].
In ovariectomized mice, in vivo administration of STO-609 (10 μM, 200 μl per mouse, i.p., thrice a week) resulted in increased osteoblasts and diminished osteoclasts, significantly protect adult mice from ovariectomy-induced osteoporosis [2].[1]. Tokumitsu H, Inuzuka H, Ishikawa Y, et al. STO-609, a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. Journal of Biological Chemistry, 2002, 277(18): 15813-15818.
[2]. Cary R L, Waddell S, Racioppi L, et al. Inhibition of Ca²⁺/calmodulin-dependent protein kinase kinase 2 stimulates osteoblast formation and inhibits osteoclast differentiation. Journal of Bone and Mineral Research, 2013, 28(7): 1599-1610.
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