GSK 2193874 |
Katalog-Nr.GC16917
One-Click Copy Product Info
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GSK 2193874 ist ein oral aktiver, potenter und selektiver TRPV4-Antagonist mit IC50-Werten von 2 nM und 40 nM für rTRPV4 und hTRPV4.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1336960-13-4
Sample solution is provided at 25 µL, 10mM.
GSK2193874 is an orally active, potent, and selective TRPV4 antagonist with IC50 of 2 nM and 40 nM for rTRPV4 and hTRPV4.
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].
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].
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.
[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.
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Animal experiment: |
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), Furosemide (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. |
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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. |
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| Cas No. | 1336960-13-4 | SDF | |
| Chemical Name | (Z)-3-([1,4'-bipiperidin]-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-(3-(trifluoromethyl)phenyl)quinoline-4-carbimidic acid | ||
| Canonical SMILES | BrC1=CC2=C(C(/C(O)=N/C3(C4=CC=CC=C4)CC3)=C(C(C5=CC(C(F)(F)F)=CC=C5)=N2)CN6CCC(N7CCCCC7)CC6)C=C1 | ||
| Formula | C37H38BrF3N4O | M.Wt | 691.62 |
| Löslichkeit | DMF: 15 mg/mL,DMSO: 14 mg/mL,Ethanol: 15 mg/mL,Ethanol:PBS (pH 7.2)(1:2): 0.3 mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4459 mL | 7.2294 mL | 14.4588 mL |
| 5 mM | 289.2 μL | 1.4459 mL | 2.8918 mL |
| 10 mM | 144.6 μL | 722.9 μL | 1.4459 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)