GSK1016790A |
| Catalog No.GC17940 |
GSK1016790A is a potent and selective transient receptor potential vanilloid 4 (TRPV4) channel agonist.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 942206-85-1
Sample solution is provided at 25 µL, 10mM.
GSK1016790A is a potent and selective transient receptor potential vanilloid 4 (TRPV4) channel agonist[1]. TRPV4 is a Ca2+-permeable, non-selective cation channel involved in a variety of physiological functions, such as regulation of systemic osmotic pressure, vascular function, skin barrier function, airway and lung function, and pain[2]. GSK1016790A is a cell-permeable piperazinamide derivative that is approximately 300 times more potent than 4-α-PDD in activating TRPV4 channels[3].
In vitro, GSK1016790A (10 nM) treatment of HeLa cells transfected with TRPV4-mCerulean and TRPV4-mVenus for 30 min resulted in rapid early activation of TRPV4 and a significant and sustained increase in cytoplasmic Ca2+ levels, which then rapidly decayed to a pseudo-steady state within approximately 3 minutes[4]. GSK1016790A (0.1-1000 nM) treatment of HEK cells induced Ca2+ influx, with EC50 values of 18 and 2.1 nM for human and mouse HEK cells, respectively[5].
In vivo, oral treatment of atherosclerotic mice with GSK1016790A (10 mg/kg) for 3 days significantly reduced the development of atherosclerotic plaques and the content of macrophages in the aortic sinus[6]. GSK1016790A (0.5 nM/5 mL) treated mice with intracerebral hemorrhage (ICH) by intraventricular injection alleviated neurological and motor deficits and upregulated the expression level of c-fos, a marker of neuronal activity[7].
References:
[1] Kittaka H, Yamanoi Y, Tominaga M. Transient receptor potential vanilloid 4 (TRPV4) channel as a target of crotamiton and its bimodal effects[J]. Pflügers Archiv-European Journal of Physiology, 2017, 469: 1313-1323.
[2] Nilius B, Voets T. The puzzle of TRPV4 channelopathies[J]. EMBO reports, 2013, 14(2): 152-163.
[3] Thorneloe K S, Sulpizio A C, Lin Z, et al. N-((1S)-1-{[4-((2S)-2-{[(2, 4-dichlorophenyl) sulfonyl] amino}-3-hydroxypropanoyl)-1-piperazinyl] carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I[J]. Journal of Pharmacology and Experimental Therapeutics, 2008, 326(2): 432-442.
[4] Jin M, Wu Z, Chen L, et al. Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A[J]. PloS one, 2011, 6(2): e16713.
[5] Fichna J, Poole D P, Veldhuis N, et al. Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission[J]. Journal of Molecular Medicine, 2015, 93: 1297-1309.
[6] Xu S, Liu B, Yin M, et al. A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis[J]. Oncotarget, 2016, 7(25): 37622.
[7] Asao Y, Tobori S, Kakae M, et al. Transient receptor potential vanilloid 4 agonist GSK1016790A improves neurological outcomes after intracerebral hemorrhage in mice[J]. Biochemical and Biophysical Research Communications, 2020, 529(3): 590-595.
| Cell experiment [1]: | |
Cell lines | HeLa cells |
Preparation Method | HeLa cells were co-transfected with TRPV4-mCerulean and TRPV4-mVenus, and fixed at 0, 3, 10 and 30 min after GSK1016790A (10 nM) treatment. |
Reaction Conditions | 10nM; 0, 3, 10 and 30 min |
Applications | GSK1016790A causes a TRPV4 specific Ca2+ influx in HeLa-TRPV4 cells, but not in control transfected cells. |
| Animal experiment [2]: | |
Animal models | ApoE−/− mice |
Preparation Method | Mice were administrated by oral gavage with vehicle or GSK101016790A (10 mg/kg body weight) daily for 3 days, and on the following day, they received an intraperitoneal (i.p.) injection of vehicle (PBS) or murine recombinant tumor necrosis factor α (TNF-α). At 4 h after vehicle or TNF-α treatment, the mice were prepared for intravital microscopy. |
Dosage form | 10 mg/kg; p.o. |
Applications | The development of atherosclerotic plaques and macrophage content in the aortic sinus were significantly reduced in mice treated with GSK101016790A. |
References: [1]Jin M, Wu Z, Chen L, et al. Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A[J]. PloS one, 2011, 6(2): e16713. [2]Xu S, Liu B, Yin M, et al. A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis[J]. Oncotarget, 2016, 7(25): 37622. | |
| Cas No. | 942206-85-1 | SDF | |
| Chemical Name | N-[(1S)-1-[[4-[(2S)-2-[[(2,4-dichlorophenyl)sulfonyl]amino]-3-hydroxy-1-oxopropyl]-1-piperazinyl]carbonyl]-3-methylbutyl]-benzo[b]thiophene-2-carboxamide | ||
| Canonical SMILES | ClC1=CC=C(S(N[C@H](C(N2CCN(C([C@@H](NC(C3=CC4=C(C=CC=C4)S3)=O)CC(C)C)=O)CC2)=O)CO)(=O)=O)C(Cl)=C1 | ||
| Formula | C28H32Cl2N4O6S2 | M.Wt | 655.6 |
| Solubility | ≤10mg/ml in ethanol;15mg/ml in DMSO;15mg/ml in dimethyl formamide | 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 | 1.5253 mL | 7.6266 mL | 15.2532 mL |
| 5 mM | 0.3051 mL | 1.5253 mL | 3.0506 mL |
| 10 mM | 0.1525 mL | 0.7627 mL | 1.5253 mL |
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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 ddH2O, 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.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)
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