TRV-120027 acetate (1234510-46-3 free base)

TRV-120027 acetate is a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1 receptor) and engages -arrestins while blocking G-protein signaling.
In vitro, TRV120027 TFA (100 nM) 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. TRV120027 TFA (100 nM) significantly increases the AT1R and TRPC3 association with the immunoprecipitated β-arrestin-1 in HEK293 cells co-transfected with Flag-AT1R-cherry, TRPC3-GFP, and HA-β-arrestin-1 ^[2].
In vivo, TRV120027 TFA (i.v.; 0.3 or 1.5 μg/kg per minute; infusion rate, 0.5 mL/min), when added to furosemide, decreases cardiac preload and afterload, systemic and renal vascular resistance, and left ventricular external work while increasing cardiac output and renal blood flow ^[1].

References:
[1]. Boerrigter G, et al. TRV120027, a novel β-arrestin biased ligand at the angiotensin II type I receptor, unloads the heart and maintains renal function when added to furosemide in experimental heart failure.Circ Heart Fail. 2012 Sep 1;5(5):627-34. Epub 2012 Aug 13.
[2]. Liu CH, et al. Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.Nat Commun. 2017 Feb 9;8:14335.

TRV-120027 acetate (1234510-46-3 free base) 是 1 型血管紧张素 II 受体（AT1 受体）的 β-arrestin-1 偏向激动剂，可与 ß-arrestins 结合，同时阻断 G 蛋白信号传导。
在体外，TRV120027 TFA（100 nM）在共转染有AT1R、β-arrestin-1和TRPC3的HEK293细胞中诱导[Ca2+]i升高，而在预先用Pyr3处理的共转染有Flag-AT1R-Cherry、HA-β-arrestin-1和TRPC3-GFP的HEK293细胞中，这一效应被显著抑制。TRV120027 TFA（100 nM）显著增加了AT1R和TRPC3与共转染Flag-AT1R-cherry、TRPC3-GFP和HA-β-arrestin-1的HEK293细胞中免疫共沉淀的β-arrestin-1的关联^[2]。
在体内，TRV120027 TFA（静脉注射；0.3或1.5μg/kg每分钟；输注速率，0.5 mL/min）与furosemide联用时，可降低心脏前负荷和后负荷、全身和肾脏血管阻力及左心室外工作量，同时增加心输出量和肾脏血流量^[1]。