GSK2193874

Cat. No.: HY-100720 Purity: 99.74%: FAQs
Data Sheet SDS COA Handling Instructions

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.

GSK2193874 Chemical Structure

CAS No. : 1336960-13-4

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solution
10 mM * 1 mL in DMSO	USD 141	In-stock	Estimated Time of Arrival: December 31
Solid + Solvent
10 mM * 1 mL ready for reconstitution	USD 141	In-stock	Estimated Time of Arrival: December 31
Solid
2 mg	USD 66	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 92	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 158	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 317	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 515	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 911	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 11 publication(s) in Google Scholar

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TRPC TRPM TRPV TRPA TRPML

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

IC50: 2 nM (rTRPV4), 40 nM (hTRPV4)^[1]

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].

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].

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

Molecular Weight

691.62

Appearance

Solid

Formula

C₃₇H₃₈BrF₃N₄O

CAS No.

1336960-13-4

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)

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

*Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in saline)
Solubility: 2.5 mg/mL (3.61 mM); Suspended solution; Need ultrasonic
2.

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (3.01 mM); Clear solution
3.

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

*All of the co-solvents are available by MCE.

Purity & Documentation

Purity: 99.74%

Select Batch:

Data Sheet (280 KB) SDS (420 KB)

COA (254 KB) LCMS (268 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]

GSK2193874 Related Classifications

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.

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Keywords:

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

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GSK2193874

Customer Review

GSK2193874 Related Antibodies

11 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

GSK2193874 Related Classifications

Molarity Calculator

Dilution Calculator

The molarity calculator equation

The dilution calculator equation

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