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500469
Sigma-AldrichRyR-Calstabin Interaction Stabilizer, S107 - CAS 927871-76-9 - Calbiochem
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.
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.
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.
Data Sheet
Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.
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.
Form
Off-white solid
Intert gas (Yes/No)
Packaged under inert gas
CAS number
927871-76-9
Chemical formula
C₁₁H₁₅NOS
Structure formula
Purity
≥98% by HPLC
Solubility
DMSO (100 mg/ml)
Storage
Protect from light +2°C to +8°C
Do Not Freeze
Ok to freeze
Special Instructions
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity
Standard Handling
References
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.
