Home Transmembrane Transporters TRP Channel inhibitor GSK2193874 For research use only.

GSK2193874

GSK2193874 is an orally active, potent, and selective blocker of transient receptor potential vanilloid 4 (TRPV4) with IC50 values of 0.04 and 0.002 μM for hTRPV4 and rTRPV4, respectively.

GSK2193874 Chemical Structure

GSK2193874 Chemical Structure

CAS No. 1336960-13-4

Purity & Quality Control

GSK2193874 Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293 Function assay 10 mins Antagonist activity at rat TRPV4 expressed in HEK293 cells assessed as inhibition of GSK634775A-induced calcium influx preincubated for 10 mins followed by GSK634775A addition by Fura-4 dye based FLIPR assay, IC50=0.002μM 28523109
HEK293 Function assay 10 mins Antagonist activity at human TRPV4 expressed in HEK293 cells assessed as inhibition of GSK634775A-induced calcium influx preincubated for 10 mins followed by GSK634775A addition by Fura-4 dye based FLIPR assay, IC50=0.04μM 28523109
HEK Function assay Antagonist activity at human TRPV4 channel transfected in HEK cells assessed as inhibition of GSK634775-evoked Ca2+ influx by FLIPR method, IC50=0.04μM 31532662
HEK Function assay Antagonist activity at human TRPV4 expressed in HEK cells assessed as inhibition of GSK634775-induced Ca2+ influx by FLIPR assay, IC50=0.05μM 30500190
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Biological Activity

Description GSK2193874 is an orally active, potent, and selective blocker of transient receptor potential vanilloid 4 (TRPV4) with IC50 values of 0.04 and 0.002 μM for hTRPV4 and rTRPV4, respectively.
Targets
rTRPV4 [1]
(Cell-free assay)		 hTRPV4 [1]
(Cell-free assay)
0.002 μM 0.04 μM
In vitro
In vitro GSK2193874 is profiled against TRP channels and is selective against TRPV1, TRPA1, TRPC3, TRPC6, and TRPM8 (IC50 > 25 μM)[1]. Treatment of human umbilical vein endothelial cells (HUVECs) with GSK2193874 dose-dependently prevents the cellular contraction and detachment induced by TRPV4 activation with GSK1016790[2].
Cell Research Cell lines Stably transfected hTRPV4 HEK cells (CG27) and HUVECs
Concentrations 1-30 nM(extracellularly); 0.03-10 uM(intracellularly)
Incubation Time --
Method

TRPV4 HEK cells were pretreated with GSK2193874, extracellularly (1-30 nM) by application to the bathing solution, or intracellularly (0.03-10 uM) by inclusion in the pipette solution. Ramp currents were elicited between -60 and +60 mV and peak outward current at +60 mV was assessed after TRPV4 activation with GSK634775 (100 nM) added to the bath. In HUVECs, ramp currents were elicited between -80 and +80 mV and measured at + 60 mV, and the TRPV4 activator GSK1016790 (30 nM) was bath applied to activate TRPV4 followed by GSK2193874 (300 nM). 
In Vivo
In vivo 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[1]. 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[2].
Animal Research Animal Models Adult male Sprague-Dawley rats
Dosages 30 mg/kg
Administration via oral gavage

Chemical Information & Solubility

Molecular Weight 691.62 Formula

C37H38BrF3N4O
CAS No. 1336960-13-4 SDF --
Smiles C1CCN(CC1)C2CCN(CC2)CC3=C(C4=C(C=C(C=C4)Br)N=C3C5=CC(=CC=C5)C(F)(F)F)C(=O)NC6(CC6)C7=CC=CC=C7
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (144.58 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 40 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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