GW-4869 HCl

• CAS: 6823-69-4
• Catalog Number: ACM6823694-1
• Category: Inhibitors
• Molecular Weight: 577.51
• Molecular Formula: C30H30Cl2N6O2
• Description: GW-4869 is a cell-permeable, non-competitive inhibitor of neutral sphingomyelinases (IC50 = 1 μM). It inhibits TNF-α-mediated sphingomyelin hydrolysis (100% inhibition at 20 μM). GW4869 is cytotoxic to high phosphatidylserine-expressing myeloma cells. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction.
• Synonyms: GW4869; GW-4869; GW 4869; GW554869A; GW-554869A; GW 554869A; GW69A; GW-69A; GW 69A; GW-4869 HCl
• IUPAC Name: (2E,2'E)-3,3'-(1,4-phenylene)bis(N-(4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)acrylamide) dihydrochloride
• Canonical SMILES: O=C(/C=C/C1=CC=C(C=C1)/C=C/C(NC2=CC=C(C=C2)C3=NCCN3)=O)NC4=CC=C(C=C4)C5=NCCN5.[H]Cl.[H]Cl
• 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+
• InChI Key: NSFKAZDTKIKLKT-CLEIDKRQSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 6823-69-4 (HCl); 475570-61-7 (free base)
• Biological Target: GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor with an IC50 of 1 μM. GW4869 is an inhibitor of exosome biogenesis/release.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 62.39; H, 5.24; Cl, 12.28; N, 14.55; O, 5.54
• Exact Mass: 576.1807
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Treatment with GW4869 dramatically reduced the number of ZIKV-positive astrocytes in the infected cultures (Fig. 6f-j). GW4869 treatment also dramatically decreased ZIKV RNA in the supernatants and reduced viral plaque numbers in PFA (Fig. 6k-m). Similarly, treatment with GW4869 significantly decreased EV numbers in ZIKV MR766 strain-infected astrocytes (Fig. 7a and b). GW4869 reduced the levels of Flotillin-2 and tTG (Tissue transglutaminase, another EV marker) in EV lysates (Fig. 7c), suggesting that GW4869 effectively reduces EVs in infected astrocytes. GW4869 treatment markedly decreased ZIKV RNA in infected astrocytes (Fig. 7d) and in supernatants (Fig. 7e). GW4869 treatment also dramatically decreased viral plaque numbers in PFA (Fig. 7f). Together, these data suggest that GW4869 is an effective inhibitor for ZIKV infection in astrocytes.; Reference: Cell Discov. 2018 Apr 24;4:19. https://pubmed.ncbi.nlm.nih.gov/29707233/
• In Vivo Activity: Circulating IL-1β was significantly reduced (47% decrease; Figure XIIA in the online-only Data Supplement) in the plasma of Apoe-/-/Smpd3+/+ mice treated by GW4869 in comparison with vehicle-treated mice and in the plasma of Apoe-/-/Smpd3fro/fro mice (57% decrease; Figure XIIB in the online-only Data Supplement). Likewise, the expression of VCAM-1, IL-1β, IL-6, and TNF-α mRNAs was reduced in aortas of mice injected with GW4869 (Figure XIII in the online-only Data Supplement), together with a decreased ceramide content (around 30%; Figure XIV in the online-only Data Supplement). Finally, the number of MoMa-2/IL-1β positive cells was decreased in the aortic sinus of mice treated by GW4869 (Figure 5A and 5B) and in Apoe-/-/Smpd3fro/fro mice (Figure 5C and 5D). Altogether, these data indicated that nSMase2 inhibition decreases vascular inflammation by reducing the recruitment of monocytes to endothelium and macrophage M1 differentiation.; Reference: Arterioscler Thromb Vasc Biol. 2018 Jul;38(7):1479-1492. https://pubmed.ncbi.nlm.nih.gov/29794115/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).