RyR-Calstabin Interaction Stabilizer, S107-Calbiochem

C₁₁H₁₅NOS

209.31

A cell-permeable, orally active benzothiazepine derivative that effectively blocks leaky intracellular calcium release by preventing the dissociation/depletion of calstabin from the ryanodine receptor (RyR) complex due to receptor modifications, such as oxidation, S-nitrosylation, PKA-mediated hyperphosphorylation, or mutation (complete blockage of 1 mM tetracaine-induced leakage in murine RyR2 S2808D^+/+ myocytes at 1 µM). Oral administration in mice (75 mg/kg/day via drinking water) is shown to prevent stress-induced cognitive dysfunction by stabilizing RyR2-calstabin-2 (FKBP12.6) interaction in brain of stressed animals. Likewise, s.c. administration (2.5 µg/0.25 µL/h/animal; by s.c. via neck dorsal surface osmotic pump implant) is reported to maintain mice exercise capacity by stabilizing RyR1-calstabin-1 (FKBP12) interaction in skeletal muscle following intensive exercise regimes. Also demonstrated to exhibit in vivo efficacy in restoring normal cardiac function in mice with R2474S (5 mg/kg/h; by s.c. via osmotic pump) or S2808D (20 mg/kg/day; by s.c. via osmotic pump) RyR2 mutation.
A cell-permeable, orally active benzothiazepine that effectively blocks leaky intracellular calcium release by preventing the dissociation/depletion of calstabin from the ryanodine receptor (RyR) complex due to receptor modifications, such as oxidation, S-nitrosylation, hyperphosphorylation, or mutation (complete blockage of 1 mM tetracaine-induced leakage in murine RyR2 S2808D^+/+ myocytes at 1 µM). Shown to prevent stress-induced cognitive dysfunction by stabilizing RyR2-calstabin-2 (FKBP12.6) interaction in brain (75 mg/kg/day; p.o.) and maintain exercise capacity by stabilizing RyR1-calstabin-1 (FKBP12) interaction in skeletal muscle (2.5 µg/0.25µL/h/animal; s.c) in mice, as well as restore normal cardiac function (20 mg/kg/day; s.c) in mice with R2474S or S2808D RyR2 mutation in vivo.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Primary Target
RyR2

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Liu, X., et al. 2012. Cell.150, 1055.

Shan, J., et al. 2010. J. Clin. Invest.120, 4375.
Bellinger, A. M., et al. 2008. Proc. Natl. Acad. Sci. USA105, 2198.
Lehnart, S.E., et al. 2008. J. Clin. Invest.118, 2230.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

100

≥98% (HPLC)

solid

Calbiochem^®

OK to freeze
protect from light

off-white

DMSO: 100 mg/mL

2-8℃

Packaged under inert gas

11 - Combustible Solids

WGK 3