GSK2193874

Catalog No.S8367 Batch:S836703

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Technical Data

Formula

C37H38BrF3N4O
Molecular Weight 691.62 CAS No. 1336960-13-4
Solubility (25°C)* In vitro DMSO 100 mg/mL (144.58 mM)
Ethanol 50 mg/mL (72.29 mM)
Water Insoluble
* <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.)

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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 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].
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].

Protocol (from reference)

Cell Assay:

[2]
  • 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). 
Animal Study:

[2]
  • Animal Models

    Adult male Sprague-Dawley rats

  • Dosages

    30 mg/kg

  • Administration

    via oral gavage

Selleck's GSK2193874 has been cited by 11 publications

Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement [ Int J Oral Sci, 2024, 16(1):3] PubMed: 38221531
Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway [ iScience, 2023, 26(5):106749] PubMed: 37216091
Dental Pulp Stem Cell-Derived Exosomes Alleviate Mice Knee Osteoarthritis by Inhibiting TRPV4-Mediated Osteoclast Activation [ Int J Mol Sci, 2023, 24(5)4926] PubMed: 36902356
Endothelial Transient Receptor Potential Vanilloid 4 Channels Mediate Lung Ischemia-Reperfusion Injury [ Ann Thorac Surg, 2022, 113(4):1256-1264] PubMed: 33961815
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] PubMed: 33761112
TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome [ Neurosci Bull, 2021, 37(7):905-920] PubMed: 33761112
Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4 [ Cell Prolif, 2020, 53(10):e12912] PubMed: 32964544
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] PubMed: 31461316
Transient Receptor Potential Ion Channels Mediate Adherens Junctions Dysfunction in a Toluene Diisocyanate-Induced Murine Asthma Model [ Toxicol Sci, 2019, 168(1):160-170] PubMed: 30517707
Transient Receptor Potential Ion Channels Mediate Adherens Junctions Dysfunction in a Toluene Diisocyanate-Induced Murine Asthma Model [ Toxicol Sci, 2019, 168(1):160-170] PubMed: 30517707

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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.