GSK2193874

Name: GSK2193874
Brand: MedChemExpress
SKU: HY-100720
Rating: 5.0 (18 reviews)

Cat. No.: HY-100720 Purity: 99.91%: Data Sheet
COA

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GSK2193874 is an orally active, potent, and selective TRPV4 antagonist with IC₅₀s of 2 nM and 40 nM for rTRPV4 and hTRPV4.

For research use only. We do not sell to patients.

CAS No. : 1336960-13-4

Size	Stock	Quantity

Free Sample (0.1 - 0.2 mg)	Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
2 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
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Customer Review

Based on 18 publication(s) in Google Scholar

Other Forms of GSK2193874:

GSK2193874 (Standard) Get quote

18 Publications Citing Use of MCE GSK2193874

Histological Imaging/Staining

ELISA

Cell Proliferation/Viability Assay

Cell Imaging/Staining

: GSK2193874 purchased from MedChemExpress. Usage Cited in: J Thorac Cardiovasc Surg. 2024 Oct;168(4):e121-e132. [Abstract]; Representative H&E-stained lung sections after 4 hours of reperfusion in vehicle- and GSK2193874 (GSK219) (30 mg/kg, p.o.)-treated recipient animals.

: GSK2193874 purchased from MedChemExpress. Usage Cited in: J Thorac Cardiovasc Surg. 2024 Oct;168(4):e121-e132. [Abstract]; IL-8 levels in BAL fluid were significantly reduced in GSK2193874 (GSK219) (30 mg/kg,p.o.)-treated animals, however, IL-1β levels were not significantly altered.

: GSK2193874 purchased from MedChemExpress. Usage Cited in: Autophagy. 2021 Nov;17(11):3592-3606. [Abstract]; Effect of various ion channel inhibitors on CBD-induced glioma cell death. U251 or LN18 cells were pretreated with GSK2193874 (5 μM) for 1 h and then treated with CBD (30 μM) for 48 h. Cell viability was determined by the MTT assay.

: GSK2193874 purchased from MedChemExpress. Usage Cited in: Autophagy. 2021 Nov;17(11):3592-3606. [Abstract]; Effect of TRPV4 inhibitor on CBD-induced mitophagy in glioma cells. U251 or U87 MG cells were treated with 20 μM CBD with or without GSK2193874 pretreatment (5 μM for 1 h), LC3 and Cl-PARP levels were analyzed by western blotting.

: GSK2193874 purchased from MedChemExpress. Usage Cited in: Autophagy. 2021 Nov;17(11):3592-3606. [Abstract]; Effect of the TRPV4 inhibitor GSK2193874 (5 μM) on CBD-induced calcium flux in glioma cells. U251 or U87 MG cells were treated with 30 μM CBD with or without GSK2193874; Ca2⁺ flux was detected by using the Ca2⁺ indicator Fluro-4AM.

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View All TRP Channel Isoform Specific Products:

View All Isoforms

TRPA1 TRPC3 TRPC4 TRPC5 TRPC6 TRPC7 TRPM8 TRPM2 TRPM3 TRPM4 TRPM7 TRPML1 TRPML2 TRPML3 TRPV1 TRPV2 TRPV3 TRPV4 TRPV6

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

GSK2193874 is an orally active, potent, and selective TRPV4 antagonist with IC₅₀s of 2 nM and 40 nM for rTRPV4 and hTRPV4^[1].

IC₅₀ & Target

hTRPV4

2 nM (IC₅₀)

rTRPV4

40 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	0.04 μM Compound: 28; GSK2193874	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 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	[PMID: 28523109]

In Vitro

GSK2193874 is profiled against TRP channels and is selective against TRPV1, TRPA1, TRPC3, TRPC6, and TRPM8 (IC₅₀>25 μM)^[1]. GSK2193874 is a selective, orally active TRPV4 blocker that inhibits Ca²⁺ influx through recombinant TRPV4 channels and native endothelial TRPV4 currents. In whole-cell patch-clamp studies, GSK2193874 inhibits activation of recombinant TRPV4 currents when applied to the extracellular solution at 3 nM and above but is ineffective at up to 10 μM when applied to the inside of the cell by inclusion in the intracellular pipette solution^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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 t_1/2=10 h, %F=31. Dog PK: iv CL=6.9 mL/min/kg, po t_1/2=31 h, %F=53). In addition, GSK2193874 shows no blood pressure or heart rate effect in rats when dose up to 30 mg/kg. GSK2193874 is the first-in-class orally bioavailable TRPV4 inhibitor that demonstrated ability to improve pulmonary functions in a number of heart failure models^[1]. GSK2193874 shows low clearance (7.3 mL/min/kg) and good rat oral bioavailability (31%)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

691.62

Formula

C₃₇H₃₈BrF₃N₄O

CAS No.

1336960-13-4

Appearance

Solid

Color

White to light yellow

SMILES

O=C(C1=C(CN2CCC(N3CCCCC3)CC2)C(C4=CC=CC(C(F)(F)F)=C4)=NC5=CC(Br)=CC=C15)NC6(C7=CC=CC=C7)CC6

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (144.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.4459 mL	7.2294 mL	14.4588 mL
5 mM	0.2892 mL	1.4459 mL	2.8918 mL
10 mM	0.1446 mL	0.7229 mL	1.4459 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (3.01 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.91%

Select Batch:

Data Sheet (280 KB) SDS (480 KB)

COA (254 KB) LCMS (97 KB)

Handling Instructions (2659 KB)

References

[1]. Cheung M, et al. Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. ACS Med Chem Lett. 2017 Mar 20;8(5):549-554. [Content Brief]

[2]. Thorneloe KS, et al. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012 Nov 7;4(159):159ra148. [Content Brief]

Animal Administration
^[2]

Rats^[2]
Adult male Sprague-Dawley rats (n=7 to 8 per group) are treated with vehicle (6% Cavitron) or GSK2193874 (30 mg/kg per day) via oral gavage for at least 4 days before osmotic challenges. Rats undergo acute and chronic hyper- and hypo-osmotic challenges. Sprague-Dawley rats are administered vehicle (0.9% NaCl, 25 mL/kg), NSC 269420 (30 mg/kg), or hydrochlorothiazide (30 mg/kg) via oral gavage. Urine is then collected over 4 hours followed by blood sampling. Rats recover for 4 days and then receive GSK2193874 (30 mg/kg per day oral gavage) for 5 days before repeating the diuretic challenge.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

[1]. Cheung M, et al. Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. ACS Med Chem Lett. 2017 Mar 20;8(5):549-554. [Content Brief]

[2]. Thorneloe KS, et al. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012 Nov 7;4(159):159ra148. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.4459 mL	7.2294 mL	14.4588 mL	36.1470 mL
	5 mM	0.2892 mL	1.4459 mL	2.8918 mL	7.2294 mL
	10 mM	0.1446 mL	0.7229 mL	1.4459 mL	3.6147 mL
	15 mM	0.0964 mL	0.4820 mL	0.9639 mL	2.4098 mL
	20 mM	0.0723 mL	0.3615 mL	0.7229 mL	1.8074 mL
	25 mM	0.0578 mL	0.2892 mL	0.5784 mL	1.4459 mL
	30 mM	0.0482 mL	0.2410 mL	0.4820 mL	1.2049 mL
	40 mM	0.0361 mL	0.1807 mL	0.3615 mL	0.9037 mL
	50 mM	0.0289 mL	0.1446 mL	0.2892 mL	0.7229 mL
	60 mM	0.0241 mL	0.1205 mL	0.2410 mL	0.6025 mL
	80 mM	0.0181 mL	0.0904 mL	0.1807 mL	0.4518 mL
	100 mM	0.0145 mL	0.0723 mL	0.1446 mL	0.3615 mL

GSK2193874 Related Classifications

Cardiovascular Disease

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

GSK21938741336960-13-4GSK 2193874GSK-2193874TRP ChannelTransient receptor potential channelsInhibitorinhibitorinhibit

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GSK2193874

Customer Review

Other Forms of GSK2193874:

GSK2193874 Related Antibodies

18 Publications Citing Use of MCE GSK2193874

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All TRP Channel Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

GSK2193874 Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

GSK2193874 Related Classifications

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