GW406381 is a novel, potent and highly selective cyclooxygenase-2 (COX-2) inhibitor that is able to attenuate spontaneous ectopic discharge in sural nerves of rats following chronic constriction injury. GW406381, as a novel COX-2 inhibitor, has a potential for the treatment of acute migraine. GW406381 has been shown to be effective in animal models of central sensitization and of inflammatory pain.

Physicochemical Properties

Molecular Formula	C21H19N3O3S
Molecular Weight	393.45886
Exact Mass	393.115
CAS #	221148-46-5
PubChem CID	9832687
Appearance	Typically exists as solid at room temperature
LogP	4.946
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	28
Complexity	607
Defined Atom Stereocenter Count	0
SMILES	CCOC1C=CC(C2=NN3N=CC=CC3=C2C2C=CC(S(=O)(C)=O)=CC=2)=CC=1
InChi Key	NXMZBNYLCVTRGB-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H19N3O3S/c1-3-27-17-10-6-16(7-11-17)21-20(19-5-4-14-22-24(19)23-21)15-8-12-18(13-9-15)28(2,25)26/h4-14H,3H2,1-2H3
Chemical Name	2-(4-ethoxyphenyl)-3-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-b]pyridazine
Synonyms	GW-406381; GW 406381; GW406381.
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
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 Vivo	GW406381 is an investigational, highly selective cyclooxygenase-2 (COX-2) inhibitor that is effective in animal models of central sensitization and of inflammatory pain.[1] GW406381 50 mg was superior to placebo on WOMAC pain subscore (mean difference from placebo -6.9 mm; P= .012). No clear dose response was observed, and the results with celecoxib were no different from those of placebo. In Study B, no dose of GW406381 was superior to placebo on the co-primary endpoints. Celecoxib was superior to placebo on all co-primary endpoints. Dose-related blood pressure and renovascular effects were seen with GW406381.[1]
References	Pain. 2007 Mar;128(1-2):78-87.;Medscape J Med. 2008;10(11):259.
Additional Infomation	GW-406381 has been used in trials studying the treatment of Pain, Trauma, Neurodynia, Dental Pain, and Hyperalgesia, among others.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~254.16 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.35 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 25.0 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: ≥ 2.5 mg/mL (6.35 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5416 mL	12.7078 mL	25.4155 mL
	5 mM	0.5083 mL	2.5416 mL	5.0831 mL
	10 mM	0.2542 mL	1.2708 mL	2.5416 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.