GSK205 |
Katalog-Nr.GC38501
One-Click Copy Product Info
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GSK205 ist ein potenter, selektiver TRPV4-Antagonist mit einem IC50 von 4,19 μM zur Hemmung des TRPV4-vermittelten Ca2+-Einstroms.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1263068-83-2
Sample solution is provided at 25 µL, 10mM.
GSK205 is a highly selective antagonist of the TRPV4 ion channel (IC50 = 4.19μM) [1]. GSK205 inhibits TRPV4 channel-mediated Ca²⁺ influx, thereby blocking activation signals triggered by mechanical stress, osmotic pressure changes, temperature, and chemical stimuli [2]. GSK205 is primarily used to study metabolic diseases, mechanical degenerative injury, and the mechanisms of inflammation and pain [3-4].
In 16HBE cells, after treatment with GSK205 (10μM; 1h), NLRP3 protein levels decreased, cleavage caspase-1 and GSDMD-N, and pro-caspase-1 and total GSDMD levels increased [5]. In HAEC cells, GSK205 (20μM; 2h) treatment induces inflammatory gene expression and NF-κB signaling [6].
In C57BL/6 mice, GSK205 (100μM; smear; single) effectively inhibits scratching behavior induced by histaminergic stimuli such as histamine, compound 48/80, or ET-1 [7]. In C57BL/6 mice, treated with GSK205 (1mM, 5mM; smear; single) showed reduced UVB-induced tissue damage from sunburn [8].
References:
[1]. Ye L, Kleiner S, Wu J, et al. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis[J]. Cell, 2012, 151(1): 96-110.
[2]. Tranter J D, Kumar A, Nair V K, et al. Mechanosensing in metabolism[J]. Comprehensive Physiology, 2024, 14(1): 5269-5290.
[3]. Fu S, Meng H, Inamdar S, et al. Activation of TRPV4 by mechanical, osmotic or pharmaceutical stimulation is anti-inflammatory blocking IL-1β mediated articular cartilage matrix destruction[J]. Osteoarthritis and cartilage, 2021, 29(1): 89-99.
[4]. Thompson C, Knight M, Gupta H, et al. Activation of TRPV4 by mechanical, osmotic or pharmaceutical stimulation is anti-inflammatory blocking IL-1β mediated articular cartilage matrix destruction[J]. Osteoarthritis and Cartilage, 2020.
[5]. Rao Y, Gai X, Xiong J, et al. Transient receptor potential cation channel subfamily V member 4 mediates pyroptosis in chronic obstructive pulmonary disease[J]. Frontiers in Physiology, 2021, 12: 783891.
[6]. Hong S G, Ashby J W, Kennelly J P, et al. Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation[J]. The Journal of Clinical Investigation, 2024, 134(13).
[7]. Chen Y, Fang Q, Wang Z, et al. Transient receptor potential vanilloid 4 ion channel functions as a pruriceptor in epidermal keratinocytes to evoke histaminergic itch[J]. Journal of Biological Chemistry, 2016, 291(19): 10252-10262.
[8]. Moore C, Cevikbas F, Pasolli H A, et al. UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling[J]. Proceedings of the National Academy of Sciences, 2013, 110(34): E3225-E3234.
| Cell experiment [1]: | |
Cell lines | 16HBE cells |
Preparation Method | Human bronchial epithelial cells (16HBE) were cultured in a medium containing 10% fetal bovine serum and 1% penicillin/streptomycin in an incubator at 37℃ with 5% CO2. 16HBE were pretreated with 10μM GSK205 for 1 hour and then stimulated with medium alone or CSE for 24 hours. Harvest 16HBE for Western blotting and qRT-PCR detection. |
Reaction Conditions | 10μM; 1h |
Applications | After treatment with GSK205, NLRP3 protein levels decreased, cleavage caspase-1 and GSDMD-N, and pro-caspase-1 and total GSDMD levels increased. |
| Animal experiment [2]: | |
Animal models | C57BL/6J mice |
Preparation Method | The dorsal area of the neck of mice was shaved before intradermal injection and topical application. Before testing, mice were acclimated to a Plexiglas box for at least 30 minutes. A pruritic agent (histamine, 500μg/50μL; 48/80, 100μg/50μL; ET-1, 25ng/50μL; chloroquine, 200μg/50μL) or saline was injected intradermally into the dorsal area of the neck via a 30-gauge needle to induce scratching behavior. Immediately after injection, the mice were returned to the box, and their scratching behavior was recorded with a Panasonic video camera for 30 minutes. The mice were observed for scratching with their hind limbs toward the shaved area on the dorsal area of the neck. A scratch was defined as lifting the hind limb toward the injection site and then returning it to the ground, regardless of the number of scratches in between. To investigate the local effects of the specific TRPV4 inhibitor GSK205 or the specific MEK inhibitor U0126 on pruritogen-induced scratching behavior, 100μL of prepared GSK205 (100μM) or U0126 (0.1mg/mL) was transdermally applied to the shaved area of the neck of mice 20 minutes before pruritogen injection. Control mice received an equal amount of placebo. |
Dosage form | 100μM; smear; single |
Applications | GSK205 effectively inhibits scratching behavior induced by histaminergic stimuli such as histamine, compound 48/80, or ET-1. |
References: | |
| Cas No. | 1263068-83-2 | SDF | |
| Canonical SMILES | CN(CCC1=CC=C(NC2=NC=C(C3=CC=CN=C3)S2)C=C1)CC4=CC=CC=C4.[H]Br | ||
| Formula | C24H25BrN4S | M.Wt | 481.45 |
| Löslichkeit | DMSO: 250 mg/mL (519.26 mM) | 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 | 2.0771 mL | 10.3853 mL | 20.7706 mL |
| 5 mM | 415.4 μL | 2.0771 mL | 4.1541 mL |
| 10 mM | 207.7 μL | 1.0385 mL | 2.0771 mL |
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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
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- Purity: >97.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)