GW 4869 (hydrochloride hydrate)

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-1-phosphate). GW 4869 is an inhibitor of neutral sphingomyelinase (IC50 = 1 µM). It is selective for neutral sphingomyelinase over acid sphingomyelinase at concentrations up to 150 µM as well as B. cereus PC-PLC, human lyso-PAF PLC, and bovine PP2A at 10 µM. GW 4869 inhibits TNF-alpha-induced sphingomyelin hydrolysis by 100% when used at a concentration of 20 µM and TNF-alpha-induced cell death in MCF-7 cells. It also reduces the inhibitory effects of oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphatidylcholine (OxPAPC) and the 5-keto-6-octendioic acid ester of 2-lysophosphatidylethanolamine (KOdiA-PE) on LPS-induction of IL-8 in human aortic endothelial cells. In vivo, GW 4869 (1 mg/kg) reverses hypoxia-induced pulmonary vasoconstriction in rats.Formal Name: 3,3'-(1,4-phenylene)bis[N-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-dihydrochloride-2-propenamide. CAS Number: 6823-69-4. Molecular Formula: C30H28N6O2 . 2HCl [XH2O]. Formula Weight: 577.5. Purity: >90%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 0.2 mg/ml. lambdamax: 346 nm. 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.Cl.Cl.O. InChi Code: InChI=1S/C30H28N6O2.2ClH.H2O/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,1H2/b15-5+,16-6+,,,. InChi Key: DKFSVQGRETYFBG-ZAKYHKHWSA-N.