TRV-120027 TFA 是一种血管紧张素 II 介导的血管收缩抑制剂,可增加心肌细胞的收缩力。它是一种偏向 β-arrestin-1 的 AT1R 激动剂,可与 ?-arrestins 结合,同时阻断 G 蛋白信号传导。 它通过阳离子通道亚家族 C3 (TRPC3) 偶联诱导急性儿茶酚胺分泌,并促进在质膜上形成由 AT1R-β-arrestin-1-TRPC3-PLCγ 组成的大分子复合物。
产品描述
TRV-120027 TFA is an angiotensin II–mediated vasoconstriction inhibitor and increases cardiomyocyte contractility. TRV-120027 TFA is a β-arrestin-1-biased AT1R agonist engaging ss-arrestins while blocking G-protein signaling[1]. TRV-120027 TFA induces acute catecholamine secretion through cation channel subfamily C3 (TRPC3) coupling and promotes the formation of a macromolecular complex composed of AT1R–β-arrestin-1–TRPC3–PLCγ at the plasma membrane.
体外活性
Treatment of 100 nM TRV-120027 TFA induces an [Ca2+]i increase in HEK293 cells co-transfected with AT1R, β-arrestin-1, and TRPC3, which are significantly blocked by Pyr3 pre-incubation in HEK293 cells co-transfected with Flag-AT1R-Cherry, HA-β-arrestin-1, and TRPC3-GFP[1]. Treatment of 100 nM TRV-120027 TFA significantly increases the AT1R and TRPC3 association with the immunoprecipitated β-arrestin-1 in HEK293 cells co-transfected with Flag-AT1R-cherry, HA-β-arrestin-1 and TRPC3-GFP[1].
体内活性
TRV-120027 TFA combined with furosemide decreases cardiac preload and afterload, systemic and renal vascular resistances, and left ventricular external work while increasing cardiac output and renal blood flow[2].
Cas No.
TP2158
分子式
C45H68F3N13O12
分子量
1040.1
别名
TRV-120027 TFA (1234510-46-3 free base)
储存和溶解度
DMSO:88 mg/mL (84.61 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years