| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
GSK205 targets the transient receptor potential vanilloid 4 (TRPV4) ion channel. It acts as an antagonist, inhibiting TRPV4-mediated Ca2+ influx into cells. TRPV4 is a calcium-permeable non-selective cation channel involved in various physiological processes, including pain perception, inflammation, and osmoregulation.
|
|---|---|
| ln Vitro |
In 3T3-F442A adipocytes, GSK205 (100 μM) efficiently clamps TRPV4 while simultaneously effectively expanding calcium influx triggered by TRPV4 agonists [1]. Treatment with GSK205 (5 μM; 4 days; T3-F442A adipocytes) increased the expression of genes related to thermogenesis (Mcp1, Mip1α, Mcp3, Rantes, Vcam, etc.) and decreased the expression of pro-inflammatory genes. This modification is similar to the variations in gene expression seen in adipocytes lacking TRPV4[1].
In vitro, GSK205 inhibits TRPV4-mediated Ca2+ influx with an IC50 of 4.19 µM. It potently antagonizes TRPV4 in 3T3-F442A cells at 100 µM. The compound is selective for TRPV4 over other ion channels. It blocks Ca(2+) signaling and may be used to reduce inflammation and pain. |
| ln Vivo |
GSK205 (10 mg/kg; i.p.; twice daily; for 7 days; for 4 weeks; C57BL/6J model) enhances the expression of thermogenic genes, including Pgc1a, Cidea, Cox8b, and Ucp1. In EPI fat, GSK205 led to a decrease in the expression of macrophage markers, pro-inflammatory chemokines, and Tnfa. GSK205 considerably enhances nasal tolerance in mice that undergo diet-induced body weight loss (DIO). Neither a substantial illness nor weight loss was observed [1].
In vivo activity data for GSK205 HBr are not extensively detailed in the available sources. The compound is being investigated for its potential to reduce inflammation and pain through TRPV4 antagonism. Specific in vivo efficacy data in animal models are not provided. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for GSK205 involves measuring its inhibition of TRPV4-mediated Ca2+ influx. Cells expressing TRPV4 are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4) and stimulated with a TRPV4 agonist (e.g., GSK1016790A) in the presence of varying compound concentrations. The IC50 is determined by quantifying the reduction in fluorescence signal.
|
| Cell Assay |
RT-PCR[1]
Cell Types: T3-F442A adipocytes Tested Concentrations: 5 μM Incubation Duration: 4 days Experimental Results: Genes responsible for thermogenesis Expression is increased and is also accompanied by a decrease in pro-inflammatory gene programs. Cellular assays are performed using cell lines expressing TRPV4, such as 3T3-F442A cells. Cells are treated with GSK205 at various concentrations and stimulated with a TRPV4 agonist. Calcium influx is measured using fluorescent calcium indicators. The compound's ability to block TRPV4-mediated calcium signaling is assessed. |
| Animal Protocol |
Animal/Disease Models: Male high-fat diet C57BL/6J mice [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; twice a day; 7 days Experimental Results: Pro-inflammatory chemokines and macrophage markers in fat leading to EPI and diminished expression of Tnfa. Dramatically improves glucose tolerance in diet-induced obese (DIO) mice. In vivo animal studies for GSK205 HBr are not detailed in the available sources. The compound is being investigated for its potential to reduce inflammation and pain, but specific animal models and dosing regimens are not described. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for GSK205 HBr are not available in the provided sources. The compound is a small molecule antagonist with an IC50 in the micromolar range. Specific PK parameters such as half-life, bioavailability, and clearance are not reported.
|
| Toxicity/Toxicokinetics |
Toxicity data for GSK205 HBr are not reported in the available sources. As a research compound, it is used for in vitro and potentially in vivo studies. Specific toxicological profiles are not available.
|
| References | |
| Additional Infomation |
GSK205 HBr is a research tool for studying TRPV4 function in pain, inflammation, and other physiological processes. It is a selective TRPV4 antagonist available from chemical suppliers for research use only.
|
| Molecular Formula |
C24H25BRN4S
|
|---|---|
| Molecular Weight |
481.4511
|
| Exact Mass |
480.098
|
| CAS # |
1263068-83-2
|
| PubChem CID |
72736243
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
30
|
| Complexity |
462
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Br[H].S1C(=C([H])N=C1N([H])C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])C1=C([H])N=C([H])C([H])=C1[H]
|
| InChi Key |
LQGOJHGNGSOUKL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H24N4S.BrH/c1-28(18-20-6-3-2-4-7-20)15-13-19-9-11-22(12-10-19)27-24-26-17-23(29-24)21-8-5-14-25-16-21;/h2-12,14,16-17H,13,15,18H2,1H3,(H,26,27);1H
|
| Chemical Name |
N-[4-[2-[benzyl(methyl)amino]ethyl]phenyl]-5-pyridin-3-yl-1,3-thiazol-2-amine;hydrobromide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~519.26 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0771 mL | 10.3853 mL | 20.7706 mL | |
| 5 mM | 0.4154 mL | 2.0771 mL | 4.1541 mL | |
| 10 mM | 0.2077 mL | 1.0385 mL | 2.0771 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
