JTV-519 hydrochloride

JTV-519 (K201) is a Ca2+-dependent blocker of sarcoplasmic reticulum Ca2+-stimulated ATPase (SERCA) and a partial agonist of ryanodine receptors in striated muscle. Antiarrhythmic and cardioprotective properties[1][2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cardiovascular Disease

JTV-519 (K201) 以剂量依赖的方式抑制由膜联蛋白 V 引起的 Ca2+ 向内移动到大单层囊泡 (LUV)。在 50 nM 膜联蛋白 V 和 400 μM Ca2+ 存在的情况下，3 μM JTV-519 对 Ca2+ 的抑制作用显著，25 μM K201 的抑制作用达到 50%[2]。

JTV-519 (0.5mg/kg/h，术前 2 h 静脉注射) 可改善 CLP 小鼠的心功能，其中与未经 JTV-519 处理的 CLP 小鼠相比，分数缩短 (FS) 和射血分数 (EF) 显著增加[3]。 Animal Model: Wild type male C57BL/6 mice weighing 18-22g with polymicrobial sepsis produced by cecal ligation and puncture (CLP) [3] Dosage: 0.5 mg/kg/h Administration: Applied intraperitoneally 2 h before the surgery Result: Improved cardiac function, where the EF and FS were significantly increased.

[1]. Darcy YL, et al. K201 (JTV519) is a Ca²⁺-Dependent Blocker of SERCA and a Partial Agonist of Ryanodine Receptors in Striated Muscle. Mol Pharmacol. 2016 Aug;90(2):106-15.  

[2]. Kaneko N, et al. Inhibition of annexin V-dependent Ca2+ movement in large unilamellar vesicles by K201, a new 1,4-benzothiazepine derivative. Biochim Biophys Acta. 1997 Nov 13;1330(1):1-7.  

[3]. Yang J, et al. Toll-like receptor 4-induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca²⁺ leakage promote cardiac contractile dysfunction in sepsis. J Biol Chem. 2018 Jan 19;293(3):794-807.