S107 is aType 1 ryanodine receptor (RyR1)stabilizer that binds RyR1 and enhances the binding affinity of calstabin-1.
In vitro activity
S107 is a small compound that enhances calstabin2 binding to RyR2 at low nanomolar concentrations and failed to interact with over 400 receptors, enzymes, and ion channels in screens using up to 10 μM of the compound. S107 has no effect on cardiac ion channels including the voltage-gated Na+, K+, and Ca2+ channels at concentrations up to 10 μM, and S107 had no effect on normal Ca2+ signaling in cells. S107 is a promising candidate drug for treating catecholaminergic polymorphic ventricular tachycardia (CPVT). S107 exerts an antiarrhythmic effect on CPVT-hiPSC-CMs. Pre-incubation with 10 μM S107, which stabilizes the closed state of the ryanodine receptor 2, significantly decreases the percentage of CPVT-hiPSC-CMs presenting DADs to 25%. S107 is thought to improve skeletal muscle function by stabilizing the RyR1-FKBP12 complex. S107 increases FKBP12 binding to RyR1 in SR vesicles in the presence of reduced glutathione and the NO-donor NOC12, with no effect in the presence of oxidized glutathione. S107 can reverse the harmful effects of redox active species on SR Ca2+ release in skeletal muscle by binding to RyR1 low affinity sites.
This compound belongs to the class of organic compounds known as benzothiazepines. These are organic compounds containing a benzene fused to a thiazepine ring (a seven-membered ring with a nitrogen atom and a sulfur atom replacing two carbon atoms).
External Descriptors
Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.
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