| Identification | Back Directory | [Name]
GW4869 | [CAS]
6823-69-4 | [Synonyms]
CS-2410
GW4869(1)
GW4869(2)
GW4869 2HCl
GW4869/GW-4869
GW69A， GW554869A
GW4869 USP/EP/BP
N-SMase Inhibitor
GW4869 dihydrochloride
GW 4869 (hydrochloride hydrate)
GW4869;GW 4869 HYDROCHLORIDE HYDRATE
N-SMase Inhibitor, GW4869 - CAS 6823-69-4 - Calbiochem
4',4''-Di-2-imidazolin-2-yl-p-benzenediacrylanilide dihydrochloride
2-PropenaMide, 3,3'-(1,4-phenylene)bis[N-[4-(4,5-dihydro-1H-iMidazol-2-yl)phenyl]-, hydrochloride (1:2) | [Molecular Formula]
C30H29N6O3X | [MDL Number]
MFCD06411564 | [MOL File]
6823-69-4.mol | [Molecular Weight]
521.59 |
| Hazard Information | Back Directory | [Uses]
GW4869 has been used:
- as an inhibitor of neutral sphingomyelinase and exosome biogenesis
- to analyse the effects of arsenic trioxide (ATO) treatment for hepatoma carcinoma HCCLM3 cells on ceramide production
- to determine the contributions of p75 neurotrophin receptor (p75NTR) and tropomyosin receptor kinase A (TrkA)- coupled pathways to nerve growth factor (NGF)-induced thermal hypersensitivity in rats
| [General Description]
GW4869 is a commonly used pharmacological agent, which inhibits exosome generation. It blocks ceramide-mediated inward budding of multivesicular bodies (MVBs) and the release of mature exosomes from MVBs. GW4869 exhibits cytotoxicity to phosphatidylserine-expressing myeloma cells. It inhibits the secretion of IFN (interferon)-α by plasmacytoid dendritic cells?(pDCs). | [Biochem/physiol Actions]
A cell-permeable, potent, specific, non-competitive inhibitor of N-SMase (neutral sphingomyelinase) | [in vivo]
GW4869 (2.5 μg/g, i.p.) causes inhibition of exosome release blocks LPS-stimulated pro-inflammatory cytokine production and cardiac inflammation in mice. GW4869 mitigates LPS-caused myocardial dysfunction and improves survival in mice[2].
GW4869 (2.5 μg/g, i.p.) blocks the production of pro-inflammatory cytokines and cardiac inflammation in CLP mice[2].
| Animal Model: | 10-12 weeks old Male wild-type C57BL/6 mice (Endotoxin-Challenged Mice)[2]. | | Dosage: | 2.5 μg/g. | | Administration: | I.P. once (1 h later, followed by an i.p. injection of LPS (2.5 μg/g, 100 μL)). | | Result: | Significantly decreased 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 significantly compared to PBS-controls, as evidenced by a 1.7-fold elevation in the AChE activity.
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| Animal Model: | 10-12 weeks old Male wild-type C57BL/6 mice (CLP Polymicrobial Sepsis Model)[2]. | | Dosage: | 2.5 μg/g. | | Administration: | I.P. once (before sham or CLP surgery). | | Result: | Decreased exosome concentration by 33% compared to mice injected with PBS in sham-surgery controls.
CLP-stimulated exosome release was significantly inhibited by pre-treatment of CLP mice compared to CLP mice pre-treated with PBS.
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