GSK2193874 was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+) influx through recombinant TRPV4 channels and native endothelial TRPV4 currents.

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

GSK 2193874, GSK2193874

白色至淡黄色粉末

DMSO : ≥ 100 mg/mL (144.59 mM)

rTRPV4 ,hTRPV4

GSK2193874 is profiled against TRP channels and is selective against TRPV1, TRPA1, TRPC3, TRPC6, and TRPM8 (IC50 > 25 μM). Treatment of human umbilical vein endothelial cells (HUVECs) with GSK2193874 dose-dependently prevents the cellular contraction and detachment induced by TRPV4 activation with GSK1016790.

The pharmacokinetic (PK) properties for GSK2193874 are evaluated in both rat and dog and found to have half-lives and oral exposure suitable for oral dosing in chronic animal models (Rat PK: iv CL = 7.3 mL/min/kg, po t1/2 = 10 h, %F =31. Dog PK: iv CL = 6.9 mL/min/kg, po t1/2 = 31 h, %F = 53). In addition, GSK2193874 shows no blood pressure or heart rate effect in rats when dose up to 30 mg/kg. It demonstrates to has the ability to improve pulmonary functions in a number of heart failure models. In both acute and chronic HF models, GSK2193874 pretreatment inhibits the formation of pulmonary edema and enhanced arterial oxygenation. TRPV4 blockade with GSK2193874 provides protection against the development of pulmonary edema and the resulting deficits in arterial oxygenation in HF models in vivo. GSK2193874 preserves endothelial cell integrity and inhibits endothelial TRPV4 currents while providing protection from formation of pulmonary edema in isolated lungs and in HF models.