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Purity: ≥98%
GW4869 HCl (GW-4869; GW-69A; GW-554869A), the dihydrochloride salt of GW4869, is a neutral, cell permeable and noncompetitive inhibitor of sphingomyelinase (SMase) (IC50 = 1 μM) and is most widely used pharmacological agent for blocking exosome generation.
| ln Vitro |
TNF-induced sphingomyelin (SM) hydrolysis was partially inhibited by GW4869 (10 μM), and SM loss was entirely prevented by the compound at 20 μM. The addition of 10–20 μM GW4869 completely inhibited the initial accumulation of ceramide; however, this effect was partially lost at later time points (24 hours). The reduction in glutathione is preceded by the effects of GW4869. Cell death is markedly inhibited by GW4869 in a dose-dependent manner [1]. GW4869 (10 or 20 μM) prevents macrophages from producing proinflammatory cytokines and releasing exosomes. The release of mature exosomes from multivesicular bodies (MVBs) and ceramide-mediated inward budding are both inhibited by GW4869 [2]. In hepatic stellate cells, GW4869 can also undo the suppression of CCN2 3'-UTR activity caused by miR-214-rich exosomes [3]. Precautions for dissolution: GW4869 is typically prepared as a stock solution in DMSO and stored at -80°C in aliquots.
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| ln Vivo |
In mice, GW4869 (2.5 μg/g, i.p.) suppresses exosome release, which prevents the production of pro-inflammatory cytokines and cardiac inflammation when stimulated by LPS. Mice's survival rate is increased and LPS-induced myocardial dysfunction is lessened by GW4869 [2]. In CLP mice, GW4869 (2.5 μg/g, ip) inhibits the production of pro-inflammatory cytokines and cardiac inflammation [2].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MCF7 human breast cancer cells. Tested Concentrations: 10-20 μM. Incubation Duration: 30 min (then treated with TNF (3 nM) followed). Experimental Results: Dramatically inhibited TNF-induced SM hydrolysis, whereas 20 μM of the compound protected completely from the loss of SM. Cell Viability Assay[2] Cell Types: Fresh RAW264.7 macrophages. Tested Concentrations: 10 or 20 μM. Incubation Duration: 2 hrs (hours) (then treated with 1 μg/mL LPS incubation ). Experimental Results: LPS-triggered exosome generation was remarkably attenuated in macrophages upon pre-treatment of macrophages with 10 μM GW4869, as evidenced by a 22% reduction in the activity of AChE. Such attenuation was further enhanced by treatment with the dose of 20 μM. |
| Animal Protocol |
Animal/Disease Models: 10-12 weeks old Male wild-type C57BL/6 mice (Endotoxin-Challenged Mice)[2].
Doses: 2.5 μg/g. Route of Administration: IP once (1 h later, followed by an ip injection of LPS ( 2.5 μg/g, 100 μL)). Experimental Results: Dramatically diminished exosome levels by 37% in sera, compared to levels collected from control mice. At 12 h after LPS injection, the levels of circulating exosomes were increased Dramatically compared to PBS-controls , as evidenced by a 1.7-fold elevation in the AChE activity. Animal/Disease Models: 10-12 weeks old Male wild-type C57BL/6 mice (CLP Polymicrobial Sepsis Model)[2]. Doses: 2.5 μg/g. Route of Administration: IP once (before sham or CLP surgery). Experimental Results: diminished exosome concentration by 33% compared to mice injected with PBS in sham-surgery controls. CLP-stimulated exosome release was Dramatically inhibited by pre-treatment of CLP mice compared to CLP mice pre- treated with PBS. |
| References |
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| Molecular Formula |
C30H28N6O2.2HCL.XH2O
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| Molecular Weight |
577.5
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| Exact Mass |
576.18
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| Elemental Analysis |
C, 62.39; H, 5.24; Cl, 12.28; N, 14.55; O, 5.54
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| CAS # |
6823-69-4
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| Related CAS # |
GW4869-13C4
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| PubChem CID |
16078967
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.577
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
856
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NC1=CC=C(C2=NCCN2)C=C1)/C=C/C3=CC=C(/C=C/C(NC4=CC=C(C5=NCCN5)C=C4)=O)C=C3.[H]Cl.[H]Cl
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| InChi Key |
NSFKAZDTKIKLKT-CLEIDKRQSA-N
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| InChi Code |
InChI=1S/C30H28N6O2.2ClH/c37-27(35-25-11-7-23(8-12-25)29-31-17-18-32-29)15-5-21-1-2-22(4-3-21)6-16-28(38)36-26-13-9-24(10-14-26)30-33-19-20-34-30;;/h1-16H,17-20H2,(H,31,32)(H,33,34)(H,35,37)(H,36,38);2*1H/b15-5+,16-6+;;
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| Chemical Name |
(E)-3-[4-[(E)-3-[4-(4,5-dihydro-1H-imidazol-2-yl)anilino]-3-oxoprop-1-enyl]phenyl]-N-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]prop-2-enamide;dihydrochloride
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| Synonyms |
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7316 mL | 8.6580 mL | 17.3160 mL | |
| 5 mM | 0.3463 mL | 1.7316 mL | 3.4632 mL | |
| 10 mM | 0.1732 mL | 0.8658 mL | 1.7316 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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