GW4869

Cas No.:	6823-69-4
Chemical Name:	GW-4869 HCl
Synonyms:	2-Propenamide,3,3'-(1,4-phenylene)bis[N-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-,dihydrochloride;2-Propenamide,3,3'-(1,4-phenylene)bis[N-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-,dihydrochlor...;GW 4869;GW 4869 (hydrochloride hydrate);GW-4869;Hydrochloride Hydrate;N,N′-Bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3,3′-p-phenylene-bis-acrylamide dihydrochloride;4',4''-Di-2-imidazolin-2-yl-p-benzenediacrylanilide dihydrochloride;GW4869
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
Formula:	C30H30Cl2N6O2
M.Wt:	577.51
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	GW4869 is a noncompetitive neutral sphingomyelinase inhibitor with an IC50 of 1 μM.
In Vivo:	Pre-treatment with GW4869 significantly impairs release of both exosomes and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pretreated with GW4869 displays lower amounts of exosomes and pro-inflammatory cytokines in the serum than control PBS-injected mice. Accordingly, GW4869 treatment diminishes the sepsis-induced cardiac inflammation, attenuates myocardial depression and prolongs survival[2].
In Vitro:	GW4869 (10 μM) partially inhibits TNF-induced sphingomyelin (SM) hydrolysis, and 20 μM of the compound is protected completely from the loss of SM. The addition of 10-20 μM GW4869 completely inhibits the initial accumulation of ceramide, whereas this effect is partially lost at later time points (24 h). The action of GW4869 occurs downstream of the drop in glutathione. GW4869 is able, in a dose-dependent manner, to significantly protect from cell death. These protective effects are accompanied by significant inhibition of cytochrome c release from mitochondria and caspase 9 activation, therefore localizing N-SMase activation upstream of mitochondrial dysfunction[1].