2. Membrane Transporter/Ion Channel Neuronal Signaling
  3. TRP Channel
  4. GSK2193874

GSK2193874 est un antagoniste oralement actif, puissant et sélectif de TRPV4 avec des IC50s de 2 nM et 40 nM pour rTRPV4 et hTRPV4.

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

GSK2193874 Chemical Structure

CAS No. : 1336960-13-4

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Solid + Solvent
10 mM * 1 mL in DMSO
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 USD 141 In-stock
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10 mM * 1 mL in DMSO USD 141 In-stock
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2 mg USD 66 In-stock
5 mg USD 92 In-stock
10 mg USD 158 In-stock
25 mg USD 317 In-stock
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Customer Review

Based on 12 publication(s) in Google Scholar

GSK2193874 Related Antibodies

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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].

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

GSK2193874 Related Antibodies
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. 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.
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
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)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

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:  5% DMSO    95% (20% SBE-β-CD in Saline)

    Solubility: 2.5 mg/mL (3.61 mM); Suspended solution; Need ultrasonic

  • Protocol 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

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

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: 99.74%

COA (254 KB) LCMS (268 KB)

Handling Instructions (2659 KB)
References
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

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.

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
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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.

Keywords:

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

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