| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GW 766994 targets the chemokine (C-C motif) receptor 3 (CCR3). It exhibits a Ki value of 13.8 nM in assays of eosinophil chemotaxis induced by CCL11 (eotaxin). By antagonizing CCR3, the compound blocks the recruitment and activation of eosinophils, key effector cells in allergic airway inflammation.
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| ln Vitro |
GW 766994 is an antagonist of chemokine receptor 3 (CCR3) that started eosinophilic kinase clinical trials [1]. In hippocampal neurons, GW 766994 (10 μM) reverses CCL11-induced increases in GSK3β, tau phosphorylation, CDK5 activation, and CDK5 phosphorylation [2].
In vitro, GW 766994 (10 μM) reverses CCL11-induced activation of CDK5, as well as phosphorylations of CDK5 and GSK3β, and reduces increased phosphorylation of tau in hippocampal neurons. The compound effectively inhibits CCR3-mediated signaling and eosinophil chemotaxis induced by CCL11. |
| ln Vivo |
In vivo, GW 766994 has demonstrated efficacy in animal models of asthma and eosinophilic bronchitis. As an orally active CCR3 antagonist, it reduces airway inflammation, eosinophil infiltration, and hyperresponsiveness. The compound's anti-inflammatory effects have been characterized in preclinical models, supporting its clinical development for respiratory diseases.
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| Enzyme Assay |
For receptor binding assays, membranes from cells expressing human recombinant CCR3 are incubated with radiolabeled ligands (e.g., [¹²⁵I]eotaxin) and varying concentrations of GW 766994. Non-specific binding is determined using excess unlabeled competitor. Bound radioactivity is measured by scintillation counting to calculate Ki values.
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| Cell Assay |
Cellular assays utilize eosinophils or cell lines expressing CCR3. Cells are pre-incubated with GW 766994 and then stimulated with CCL11 (eotaxin). Chemotaxis is measured using Boyden chamber or transwell assays. Intracellular calcium mobilization is measured using fluorescence-based assays. Inhibition of CCR3-mediated signaling is assessed by measuring downstream phosphorylation events.
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| Animal Protocol |
In vivo studies are conducted in murine models of allergic airway inflammation. Animals are sensitized and challenged with allergen (e.g., ovalbumin), and GW 766994 is administered orally. Endpoints include bronchoalveolar lavage (BAL) cell counts (especially eosinophils), airway hyperresponsiveness measured by methacholine challenge, and lung histology for assessment of inflammation and remodeling.
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| ADME/Pharmacokinetics |
GW 766994 is orally bioavailable with favorable pharmacokinetic properties suitable for once-daily dosing. As a small-molecule CCR3 antagonist, it shows good systemic exposure and tissue distribution. The compound has been advanced into clinical trials, indicating acceptable pharmacokinetic and safety profiles.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated GW 766994 in animal models, demonstrating a manageable safety profile. As a CCR3 antagonist, the compound is expected to have immunomodulatory effects related to its mechanism of action. Clinical trials have assessed its safety and tolerability in patients with asthma and eosinophilic bronchitis.
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| References |
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| Additional Infomation |
GW 766994 is a selective CCR3 antagonist that has entered clinical trials for asthma and eosinophilic bronchitis. Its mechanism involves blocking the CCR3 receptor, thereby inhibiting eosinophil chemotaxis and activation induced by CCL11 (eotaxin) and other CCR3 ligands. By reducing eosinophilic inflammation, the compound aims to improve respiratory function and reduce symptoms in allergic airway diseases.
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| Molecular Formula |
C21H24CL2N4O3
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|---|---|
| Molecular Weight |
451.346262931824
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| Exact Mass |
450.122
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| CAS # |
408303-43-5
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| PubChem CID |
10218765
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
685.8±55.0 °C at 760 mmHg
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| Flash Point |
368.5±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.608
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
575
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CO[C@H](CN1CC2=CC(=C(C=C2)Cl)Cl)CNC(=O)NCC3=CC=C(C=C3)C(=O)N
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| InChi Key |
GPLUUMAKBFSDIE-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C21H24Cl2N4O3/c22-18-6-3-15(9-19(18)23)12-27-7-8-30-17(13-27)11-26-21(29)25-10-14-1-4-16(5-2-14)20(24)28/h1-6,9,17H,7-8,10-13H2,(H2,24,28)(H2,25,26,29)/t17-/m0/s1
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| Chemical Name |
4-[[[(2S)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylcarbamoylamino]methyl]benzamide
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| Synonyms |
GW-766994; GW-994; GW766994; GW994; GW 766994; GW 994
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~56 mg/mL (~124.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.33 mg/mL (5.16 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 23.3 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: ≥ 2.33 mg/mL (5.16 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 23.3 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: ≥ 2.33 mg/mL (5.16 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 | 2.2156 mL | 11.0779 mL | 22.1558 mL | |
| 5 mM | 0.4431 mL | 2.2156 mL | 4.4312 mL | |
| 10 mM | 0.2216 mL | 1.1078 mL | 2.2156 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.
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