In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml
Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
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 (Cell-free assay)
hTRPV4 (Cell-free assay)
0.002 μM
0.04 μM
In vitro
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 this compound dose-dependently prevents the cellular contraction and detachment induced by TRPV4 activation with GSK1016790.
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, this compound 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, this compound pretreatment inhibits the formation of pulmonary edema and enhanced arterial oxygenation. TRPV4 blockade with this chemical provides protection against the development of pulmonary edema and the resulting deficits in arterial oxygenation in HF models in vivo. This compound preserves endothelial cell integrity and inhibits endothelial TRPV4 currents while providing protection from formation of pulmonary edema in isolated lungs and in HF models.
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 this compound (300 nM).
Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway
[ iScience, 2023, 26(5):106749]
TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome
[ Neurosci Bull, 2021, 10.1007/s12264-021-00662-3]
TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome
[ Neurosci Bull, 2021, 37(7):905-920]
Regulation of mitochondrial fragmentation in microvascular endothelial cells isolated from the SU5416/hypoxia model of pulmonary arterial hypertension.
[ Am J Physiol Lung Cell Mol Physiol, 2019, 317(5):L639-L652]
RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.
SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.
