GW 4869 dihydrocloride

• CAT Number: M024107
• CAS Number: 6823-69-4
• Molecular Formula: C₃₀H₂₈N₆O₂ · 2HCl [xH₂O]
• Molecular Weight: 577.5
• Purity: ≥95%
• Synonyms: N-SMase Inhibitor;2-PropenaMide, 3,3/’-(1,4-phenylene)bis[N-[4-(4,5-dihydro-1H-iMidazol-2-yl)phenyl]-, hydrochloride (1:2);4/’,4/’/’-Di-2-imidazolin-2-yl-p-benzenediacrylanilide dihydrochloride;GW 4869 (hydrochloride hydrate)
• Target: Phospholipase
• Storage: -20°C
• InChI: 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+
• InChIKey: NSFKAZDTKIKLKT-CLEIDKRQSA-N
• SMILES: C1CN=C(N1)C2=CC=C(C=C2)NC(=O)C=CC3=CC=C(C=C3)C=CC(=O)NC4=CC=C(C=C4)C5=

Neutral sphingomyelinases mediate the release of ceramide from sphingomyelin in cellular membranes and can be activated by certain stresses. Ceramide can act as a signaling molecule in its own right, or it can be further processed to generate sphingosine (and sphingosine-<wbr></wbr>1-<wbr></wbr>phosphate). GW 4869 is a cell-<wbr></wbr>permeable, non-<wbr></wbr>competitive inhibitor of neutral sphingomyelinases (IC50 = 1 μM), but does not affect acid sphingomyelinase activity. It inhibits TNF-<wbr></wbr>α-<wbr></wbr>mediated sphingomyelin hydrolysis (100% inhibition at 20 μM) and TNF-<wbr></wbr>α-<wbr></wbr>induced cell death in MCF-7 cells without interfering with activation of NF-<wbr></wbr>κB or glutathione depletion in response to TNF. GW 4869 also reduces the inhibitory effect of oxidized phospholipid products on lipopolysaccharides-<wbr></wbr>mediated induction of interleukin-<wbr></wbr>8 in human aortic endothelial cells and prevents hypoxia-<wbr></wbr>induced pulmonary vasoconstriction in rats in vivo.