S107-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemES107 hydrochlorideCat. No.: HY-15292ACAS No.: 1357476-46-0分式: CHClNOS分量: 245.77作靶點(diǎn): Others作通路: Others儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) H2O : 132 mg/mL (537.09 mM)* means soluble, but

2、 saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 4.0688 mL 20.3442 mL 40.6884 mL5 mM 0.8138 mL 4.0688 mL 8.1377 mL10 mM 0.4069 mL 2.0344 mL 4.0688 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 S107 hydrochlorideRyR-選擇性1,4-苯并硫氮雜衍物。其通過增強(qiáng)calstabin2對突變體和/或PK-

3、磷酸化通道的結(jié)合親和來穩(wěn)定RyR2通道。體外研究S107 is a small compound that enhances calstabin2 binding to RyR2 at low nanomolar concentrations andfailed to interact with over 400 receptors, enzymes, and ion channels in screens using up to 10 M of thecompound. S107 has no effect on cardiac ion channels including the volt

4、age-gated Na+, K+, and Ca2+1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEchannels at concentrations up to 10 M, and S107 had no effect on normal Ca2+ signaling in cells 1. S107is a promising candidate drug for treating catecholaminergic polymorphic ventricular tachycardia (CPVT).S107 exerts an an

5、tiarrhythmic effect on CPVT-hiPSC-CMs. Pre-incubation with 10 M S107, which stabilizesthe closed state of the ryanodine receptor 2, significantly decreases the percentage of CPVT-hiPSC-CMspresenting DADs to 25% 2. S107 is thought to improve skeletal muscle function by stabilizing the RyR1-FKBP12 com

6、plex. S107 increases FKBP12 binding to RyR1 in SR vesicles in the presence of reducedglutathione and the NO-donor NOC12, with no effect in the presence of oxidized glutathione. S107 canreverse the harmful effects of redox active species on SR Ca2+ release in skeletal muscle by binding toRyR1 low aff

7、inity sites 3.體內(nèi)研究 S107, which prevents a leak in the channel but does not block the channel or alter normal Ca2+ signaling, isable to inhibit both seizures and arrhythymias in the mutant mice 1.PROTOCOLAnimal Mice 1Administration 1 To test for protection against seizures using S107, osmotic pumps a

8、re implanted, and mice are pretreatedwith S107 5 mg/kg/h for 1 week prior to seizure susceptibility testing. Phase 4 seizures associated with deathcould be avoided through intubation and artificial breathing, indicating diaphragm failure during sustainedseizures as a potential cause of death. Mice a

9、re directly observed and videorecorded for later review andlatency classification during a 60-minute observation period 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lehnart SE, et al. Leaky Ca2+ release channel/ryanodine receptor 2 cau

10、ses seizures and sudden cardiac death in mice. J Clin Invest.2008 Jun;118(6):2230-45.2. Sasaki K, et al. Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as aPotential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia. PLoS One. 2016 Oct 20;11(10):e0164795.3. Mei Y, et al. Stabilization of the skeletal muscle ryanodine receptor ion channel-FKBP12 complex by the 1,4-benzothiazepine derivativeS107. PLoS One. 2013;8(1):e54208.McePdfHeightCaution: Product has not been