S107 hydrochloride |
Catalog No.GC37578
One-Click Copy Product Info
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S107 hydrochloride is a small molecule compound that can specifically bind to RyR2, enhance calstabin2 binding, and inhibit Ca2+ leakage in RyR2 channels. S107 hydrochloride has oral activity and can penetrate the blood-brain barrier .
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1357476-46-0
Sample solution is provided at 25 µL, 10mM.
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S107 hydrochloride is a small molecule compound that can specifically bind to RyR2, enhance calstabin2 binding, and inhibit Ca2+ leakage in RyR2 channels. S107 hydrochloride has oral activity and can penetrate the blood-brain barrier [1-2]. S107 hydrochloride can improve muscle function, prevent arrhythmia, and increase seizure threshold by stabilizing RyR FKBP complex, making it a promising candidate drug for the treatment of catechol polymorphic ventricular tachycardia (CPVT)[3-5].
In vitro, treatment of cardiomyocytes(carrying RyR2-I4587V mutation; CPVT-hiPSC-CMs) isolated from CPVT patients with 10μM S107 hydrochloride for 2-3h inhibited the frequency of DAD (Delayed Afterdepolarization) in cells in a concentration-dependent manner, producing an antiarrhythmic effect[3]. Treatment of Rbm20 KO rat cardiomyocytes with S107 hydrochloride (10μM) for 2-3h restored the damaged contractile properties of the cells to the level of WT cardiomyocytes, inhibited Ca2+ leakage, restored the intracellular Ca2+ level at rest, and alleviated the increase in ΔFFI caused by electrical stimulation[4].
In vivo, treatment of Ryr2-R2474S epilepsy model mice with an implantable osmotic pump and a dosage of 5mg/kg/h using S107 hydrochloride for 7 days can restore brain RyR channel activity to normal levels, repair mutated channel Ca2+ leakage, and prevent fatal arrhythmias[1]. S107 hydrochloride was administered to Huntington's disease model mice via drinking water at a dose of 75mg/kg/d for one month, preventing the dissociation of calstabin2 from cardiac RyR2, reducing endoplasmic reticulum Ca2+ leakage, and significantly improving motor coordination disorder and cognitive dysfunction[6]. Male arrhythmia mice with C57BL/10ScSc-Dmdmdx/J ingested S107 hydrochloride (25mg/100mL) daily in drinking water, which inhibited the depletion of calstabin1 in the RyR1 macromolecular complex in skeletal muscle, prevented the increase in the frequency of spontaneous SR Ca2+ release events, and alleviated the abnormal electrocardiogram and ventricular arrhythmia in mice[7].
References:
[1]. Lehnart S E, Mongillo M, Bellinger A, et al. Leaky Ca 2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice[J]. The Journal of clinical investigation, 2008, 118(6): 2230-2245.
[2]. Mei Y, Xu L, Kramer H H, et al. Stabilization of the skeletal muscle ryanodine receptor ion channel-FKBP12 complex by the 1, 4-benzothiazepine derivative S107[J]. Biophysical Journal, 2013, 104(2): 443a.
[3]. Sasaki K, Makiyama T, Yoshida Y, et al. Patient-specific human induced pluripotent stem cell model assessed with electrical pacing validates S107 as a potential therapeutic agent for catecholaminergic polymorphic ventricular tachycardia[J]. PLoS One, 2016, 11(10): e0164795.
[4]. Guo W, Zhu C, Yin Z, et al. The ryanodine receptor stabilizer S107 ameliorates contractility of adult Rbm20 knockout rat cardiomyocytes[J]. Physiological Reports, 2021, 9(17): e15011.
[5]. Popa M A. Effect of Experimental Drug S107 on Accessory Protein Binding to the RyR[J]. 2012.
[6]. Dridi H, Liu X, Yuan Q, et al. Role of defective calcium regulation in cardiorespiratory dysfunction in Huntington’s disease[J]. JCI insight, 2020, 5(19): e140614.
[7]. Fauconnier J, Thireau J, Reiken S, et al. Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy[J]. Proceedings of the National Academy of Sciences, 2010, 107(4): 1559-1564.
| Cell experiment [1]: | |
Cell lines | Rbm20 KO rat cardiomyocytes |
Preparation Method | Isolation of cardiomyocytes from 6-month-old Rbm20 KO rats. Cardiomycoytes were treated with 10µM of freshly prepared S107 hydrochloride and incubated for 2-3h at room temperature prior to the experiments and cardiomyocytes treated with vehicle were served as control. Using the SoftEdge Myocam system to record cell and sarcomere length, capturing changes in myocardial cell length during shortening and re lengthening, and detecting transient intracellular Ca2+ levels using Fura-2 AM (0.5μM). |
Reaction Conditions | 10μM; 2-3h |
Applications | The treatment with S107 hydrochloride was able to restore the contractile properties of damaged cells to the level of WT cardiomyocytes, inhibit Ca2+ leakage, restore resting intracellular Ca2+ levels, and alleviate the increase in ∆FFI caused by electrical stimulation. |
| Animal experiment [2]: | |
Animal models | Q175-Z heterozygous mice exhibiting pathological status of Huntington's disease |
Preparation Method | The S107 hydrochloride was administered in drinking water at for 1 month as previously described. Mouse brain tissue samples were taken for immunohistochemistry. Take a frozen diaphragm strip from the left middle segment of the mouse rib diaphragm to measure the cross-sectional area of the diaphragm fibers, and test the contractile function of the mouse diaphragm or soleus muscle samples. |
Dosage form | 75mg/kg/d; 1 month; p.o. |
Applications | S107 hydrochloride can prevent the dissociation of calstabin2 from the heart RyR2, reduce the leakage of Ca2+ from the endoplasmic reticulum, significantly improve motor coordination disorders and cognitive dysfunction, and restore diaphragmatic muscle strength in mice. |
References: | |
| Cas No. | 1357476-46-0 | SDF | |
| Canonical SMILES | COC1=CC=C2SCCN(CC2=C1)C.Cl | ||
| Formula | C11H16ClNOS | M.Wt | 245.77 |
| Solubility | 100mg/ml in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0688 mL | 20.3442 mL | 40.6884 mL |
| 5 mM | 813.8 μL | 4.0688 mL | 8.1377 mL |
| 10 mM | 406.9 μL | 2.0344 mL | 4.0688 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)