GSK205 is a highly efficient and selective TRPV4 antagonist (inhibitor) with IC50 of 4.19 μM, which can inhibit TRPV4-mediated Ca2+ influx.

Physicochemical Properties

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)

Biological Activity

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].
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].
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.
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.
References	[1]. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell. 2012 Sep 28;151(1):96-110. [2]. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep. 2016 Jun 1;6:26894.

Solubility Data

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.