567715
N-SMase Inhibitor, GW4869
The N-SMase Inhibitor, GW4869, also referenced under CAS 6823-69-4, controls the biological activity of N-SMase. This small molecule/inhibitor is primarily used for Cell Signaling applications.
Synonym(s):
N-SMase Inhibitor, GW4869, Sphingomyelinase, Neutral, Inhibitor GW4869, GW69A, GW554869A
Sign Into View Organizational & Contract Pricing
All Photos(1)
About This Item
Empirical Formula (Hill Notation):
C30H28N6O2 · 2HCl
CAS Number:
Molecular Weight:
577.50
UNSPSC Code:
12352200
NACRES:
NA.77
Quality Level
Assay
≥90% (NMR)
form
solid
manufacturer/tradename
Calbiochem®
storage condition
OK to freeze
desiccated (hygroscopic)
protect from light
color
pale yellow
solubility
DMSO: 200 μg/mL
shipped in
wet ice
storage temp.
−20°C
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
General description
A cell permeable, symmetrical dihydroimidazolo-amide that acts as a potent, specific, and non-competitive inhibitor of neutral sphingomyelinase (N-SMase) (IC50 = 1 µM, rat brain N-SMase). Reported to inhibit tumor necrosis factor α (TNF-α) induced sphingomyelin hydrolysis (100% inhibition at 20 µM) and TNF-α-induced cell death in MCF7 cells. Does not interfere with other TNF-α-mediated signaling events, such as de novo ceramide synthesis and NF-κB activation and nuclear translocation. Exhibits no effect on cellular glutathione levels that are normally reduced in response to TNF-α. Does not inhibit acid sphingomyelinase (A-SMase) or bacterial phosphatidylcholine-specific phospholipase C (PC-PLC). Shown to weakly inhibit bovine protein phosphatase 2A (PP2A) and human lyso-PAF PLC, an enzyme that hydrolyzes sphingomyelin in vitro.
A cell-permeable, symmetrical dihydroimidazolo-amide compound that acts as a potent, specific, non-competitive inhibitor of N-SMase (neutral sphingomyelinase) [IC50 = ~ 1 µM, rat brain; Km for sphingomyelin ~13 µM]. Does not inhibit human A-SMase (acid sphingomyelinase) even at 150 µM. Weakly inhibits the activities of bovine protein phosphatase 2A and mammalian lyso-PAF PLC, while no inhibition is observed for bacterial phosphatidylcholine-specific PLC. Reported to offer complete protection against TNF-α or diamine-induced cell death in MCF7 breast cancer cells at 20 µM. Does not modify the intracellular glutathione levels or interfere with TNF-α or diamine-mediated signaling effects.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
N-Smase rat brain
N-Smase rat brain
Product does not compete with ATP.
Reversible: no
Target IC50: 1 µM rat brain N-SMase (neutral sphingomyelinase); Km for sphingomyelin ~13 µM
Packaging
Packaged under inert gas
Warning
Toxicity: Standard Handling (A)
Reconstitution
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Marchesini, N., et al. 2003. J. Biol. Chem. In press.
Luberto, C., et al. 2002. J. Biol. Chem.277, 41128
Okamoto, Y., et al. 2002. FEBS Lett.530, 140.
Luberto, C., et al. 2002. J. Biol. Chem.277, 41128
Okamoto, Y., et al. 2002. FEBS Lett.530, 140.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
WGK
WGK 3
Flash Point(F)
Not applicable
Flash Point(C)
Not applicable
Certificates of Analysis (COA)
Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.
Already Own This Product?
Find documentation for the products that you have recently purchased in the Document Library.
Adipose-derived stem cell exosome NFIC improves diabetic foot ulcers by regulating miR-204-3p/HIPK2.
Huimin Huang et al.
Journal of orthopaedic surgery and research, 18(1), 687-687 (2023-09-15)
Diabetic foot ulcers (DFU) are a serious complication of diabetes that lead to significant morbidity and mortality. Recent studies reported that exosomes secreted by human adipose tissue-derived mesenchymal stem cells (ADSCs) might alleviate DFU development. However, the molecular mechanism of
Lara Ottaviani et al.
Molecular therapy : the journal of the American Society of Gene Therapy, 30(6), 2257-2273 (2022-03-13)
As mediators of intercellular communication, extracellular vesicles containing molecular cargo, such as microRNAs, are secreted by cells and taken up by recipient cells to influence their cellular phenotype and function. Here we report that cardiac stress-induced differential microRNA content, with
Christian M Garrido et al.
Scientific reports, 10(1), 9120-9120 (2020-06-06)
K-Ras must interact primarily with the plasma membrane (PM) for its biological activity. Therefore, disrupting K-Ras PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we found that avicin G, a family of natural plant-derived triterpenoid saponins
Cuiqi Zhou et al.
The Journal of clinical endocrinology and metabolism, 107(2), 379-397 (2021-09-02)
The identification and biological actions of pituitary-derived exosomes remain elusive. This work aimed to validate production of exosomes derived from human and rat pituitary and elucidate their actions. Isolated extracellular vesicles (EVs) were analyzed by Nanoparticle Tracking Analysis (NTA) and
Jian Shi et al.
Cell reports, 33(1), 108225-108225 (2020-10-08)
Endogenous PIEZO1 channels of native endothelium lack the hallmark inactivation often seen when these channels are overexpressed in cell lines. Because prior work showed that the force of shear stress activates sphingomyelinase in endothelium, we considered if sphingomyelinase is relevant
Our team of scientists has experience in all areas of research including Life Science, Material Science, Chemical Synthesis, Chromatography, Analytical and many others.
Contact Technical Service