| Bioactivity | S107 is an orally available, blood brain barrier-permeable compound, which stabilizes RyR2 channels by enhancing the binding of calstabin 2 to the mutant Ryr2-R2474S channel. S107 inhibits Ca2+ leakage from the sarcoplasmic reticulum (SR) and prevents cardiac arrhythmias and raises the seizure threshold[1][2]. | ||||||||||||
| Invitro | S107 是一种小化合物，可以在低纳摩尔浓度下增强钙稳定蛋白 2 与 RyR2 的结合，并且在使用高达 10 μM 的浓度时，在屏幕上无法与400多种受体，酶和离子通道相互作用[1]。S107 对 CPVT-hiPSC-CMs 具有抗心律失常作用。10 μM S107 预孵育稳定了 Ryanodine 受体 2 的闭合状态，显著降低了 25% 的 CPVT-hiPSC-CMs 呈递的 DADs[2]。在还原性谷胱甘肽和 NO 供体 NOC12 存在的情况下，S107 增加了 SR 囊泡中 FKBP12 与 RyR1 的结合，而在氧化性谷胱甘肽存在的情况下没有影响。S107 可以通过结合 RyR1 低亲和力位点逆转氧化还原活性物质对 SR Ca2+ 在骨骼肌中的释放的有害影响[3]。 | ||||||||||||
| In Vivo | S107 可以防止通道泄漏，但不会阻断通道或改变正常的 Ca2+ 信号，能够抑制突变小鼠的癫痫发作和心律失常[1]。 | ||||||||||||
| Name | S107 | ||||||||||||
| CAS | 927871-76-9 | ||||||||||||
| Formula | C11H15NOS | ||||||||||||
| Molar Mass | 209.31 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Lehnart SE, et al. Leaky Ca2+ release channel/ryanodine receptor 2 causes 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 a Potential 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 derivative S107. PLoS One. 2013;8(1):e54208. |