| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
GW-406381 targets cyclooxygenase-2 (COX-2) with high selectivity. It exhibits an IC50 of 3 nM for COX-2 and an IC50 greater than 84.2 μM for COX-1, demonstrating >28,000-fold selectivity for COX-2 over COX-1. By selectively inhibiting COX-2, the compound reduces the production of pro-inflammatory prostaglandins while sparing COX-1-mediated physiological functions.
|
|---|---|
| ln Vitro |
In vitro, GW-406381 demonstrates potent and selective COX-2 inhibition with an IC50 of 3 nM. The compound's high selectivity for COX-2 over COX-1 (>28,000-fold) distinguishes it from traditional NSAIDs. This selectivity profile suggests a favorable gastrointestinal safety profile compared to non-selective COX inhibitors.
|
| 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] In vivo, GW-406381 attenuates spontaneous ectopic discharge in the sural nerves of rats following chronic constriction injury, indicating both peripheral and central analgesic effects. The compound has been evaluated in animal models of central sensitization and inflammatory pain, demonstrating efficacy in reducing pain behaviors. |
| Enzyme Assay |
For COX enzyme inhibition assays, recombinant human COX-1 and COX-2 enzymes are incubated with arachidonic acid substrate and varying concentrations of GW-406381. The production of prostaglandins (PGE2) is measured by ELISA or radioimmunoassay. IC50 values for COX-1 and COX-2 are calculated from dose-response curves.
|
| Cell Assay |
Cellular assays utilize cell lines expressing COX-2 (e.g., LPS-stimulated macrophages). Cells are treated with GW-406381 at various concentrations, and PGE2 production in the culture medium is measured by ELISA. The compound's ability to inhibit COX-2-mediated prostaglandin synthesis is assessed, confirming its cellular activity.
|
| Animal Protocol |
In vivo studies are conducted in rat models of chronic constriction injury or inflammatory pain. GW-406381 is administered orally or intraperitoneally, and pain behaviors are assessed using von Frey filaments (mechanical allodynia) or hot plate tests (thermal hyperalgesia). Nerve recordings may be performed to measure ectopic discharges from injured nerves.
|
| ADME/Pharmacokinetics |
GW-406381 (molecular weight 393.46) is a small-molecule COX-2 inhibitor with good oral bioavailability. It is soluble in DMSO (80 mg/mL, 203.32 mM). For in vivo administration, the compound can be formulated in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity studies have shown that GW-406381, as a selective COX-2 inhibitor, has a more favorable gastrointestinal safety profile compared to non-selective NSAIDs. However, like other COX-2 inhibitors, it may be associated with cardiovascular risks. The compound's high selectivity for COX-2 minimizes COX-1-mediated gastrointestinal toxicity.
|
| References | |
| Additional Infomation |
GW-406381 has been used in trials to study the treatment of pain, trauma, neuralgia, toothache, and hyperalgesia.
GW-406381 is a highly selective COX-2 inhibitor developed for the treatment of inflammatory pain and central sensitization. Its mechanism involves selective inhibition of COX-2, reducing the production of pro-inflammatory prostaglandins in both peripheral and central nervous system tissues. The compound's high selectivity for COX-2 over COX-1 (>28,000-fold) provides a favorable therapeutic index for pain management. |
| 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)
|
| 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. View More
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. |
| 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.
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
COA