GW4869

For research use only.

Catalog No.S7609 Synonyms: GW69A, GW554869A

9 publications

GW4869 Chemical Structure

Molecular Weight(MW): 577.5

GW4869 is a neutral, noncompetitive inhibitor of sphingomyelinase (SMase) with an IC50 of 1 μM. It is selective for N-SMase, and does not inhibit acid SMase at up to at least 150 μM.

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Selleck's GW4869 has been cited by 9 publications

1 Customer Review

  • U87 and SG2 cells cultured in the indicated conditions for 48 h were exposed to TMZ for 12 h and then were stained with γ-H2AX immediately. Scale bar: 5 μm

    Cancer Lett, 2018, 433:210-220. GW4869 purchased from Selleck.

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Biological Activity

Description GW4869 is a neutral, noncompetitive inhibitor of sphingomyelinase (SMase) with an IC50 of 1 μM. It is selective for N-SMase, and does not inhibit acid SMase at up to at least 150 μM.
Targets
SMase [1]
(Cell-free assay)
1 μM
In vitro

GW4869 inhibits N-SMase not only in vitro but also in a cellular model. GW4869 does not significantly impair TNF-induced NF-κB translocation to nuclei. Therefore, GW4869 does not interfere with other key TNF-mediated signaling effects. GW4869 is able, in a dose-dependent manner, to significantly protect from cell death as measured by nuclear condensation, caspase activation, PARP degradation, and trypan blue uptake. 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. At up to 150 μM, GW4869 does not inhibit the cloned human A-SMase. GW4869 shows no or minor inhibitory activity versus other hydrolytic enzymes, such as bacterial phosphatidylcholine-PLC and bovine protein phosphatase 2A, and it shows significantly higher activity versus the rat brain enzyme compared with the human lyso-PAF PLC[1].
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MCF7 MUTGeY5kfGmxbjDhd5NigQ>? MX6xNE0zOCEQvF2= MmDNeIhmKGGmZHn0bY9vKG:oIEGwJO69VSCJV{S4Olkhe2mpbnnmbYNidnSueTDpcohq[mm2ZXSgWG5HNWmwZIXj[YQhW01iaInkdo9tgXOrczyge4hmemWjczCyNEDPxE1ib3[geIhmKGOxbYDveY5lKHC{b4TlZ5Rm\CClb33wcIV1\Wy7IH\yc40hfGinIHzvd5Mhd2Zic4DobY5od227ZXzpci=> MnPJNVIyPTRyOUi=
OPM2 MlzlVJJwdGmoZYLheIlwdiCjc4PhfS=> Mnf2NEwhOS5{NTygNk42NCB3LDCxNEwhOjBuIESwJO69dW:uL1y= MX6yOEBp MWH0bIUh[2WubDDwdo9tcW[ncnH0bY9vKHKjdHWge4F{KGmwY4LlZZNm\CCjZoTldkBIXzR6NkmgeJJm[XSvZX70MkBVcGViaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44hf2G|IH;ucJkhe2mpbnnmbYNidnRid3jlckB1cGViY3;uZ4VvfHKjdHnvckBw\iCJV{S4Olkhf2G|IESwJO69dW:uL1ygc5IhcGmpaHXyMi=> Mo\lNlg5PTh{OUS=
RPMI-8226 NF;v[pZE\WyuII\pZYJqdGm2eTDhd5NigQ>? NIXOVWk4OiCq NXXTPZZ2[3m2b4TvfIlkKHSxIHGgdIFv\Wxib3[gUW0h[2WubDDsbY5mew>? NYjl[4FpOjh{MUG1O|M>
NCI-H929 MVvD[YxtKH[rYXLpcIl1gSCjc4PhfS=> M4TTRlczKGh? MUnjfZRwfG:6aXOgeI8h[SCyYX7lcEBw\iCPTTDj[YxtKGyrbnXz M4SydFI5OjFzNUez
JJN3 NFP0d2FE\WyuII\pZYJqdGm2eTDhd5NigQ>? NXWwSYF6PzJiaB?= M4H0T4N6fG:2b4jpZ{B1dyCjIIDhcoVtKG:oIF3NJINmdGxibHnu[ZM> M3GwSFI5OjFzNUez
U266 Mo\5R4VtdCC4aXHibYxqfHliYYPzZZk> NW[w[I5jPzJiaB?= NFHteI9kgXSxdH;4bYMhfG9iYTDwZY5mdCCxZjDNUUBk\WyuIHzpcoV{ MV2yPFIyOTV5Mx?=
Daudi NFzq[Y9E\WyuII\pZYJqdGm2eTDhd5NigQ>? NILiTZo4OiCq M3e2c45wfCCleYTveI95cWNidH:gco9vNU2PIHPlcIwhdGmwZYOgc5IhWEKPQ4O= M1PzW|I5OjFzNUez
Jurkat NWHKSGZWS2WubDD2bYFjcWyrdImgZZN{[Xl? NUD6TXZ6PzJiaB?= NFTIeXpvd3RiY4n0c5RwgGmlIITvJI5wdi2PTTDj[YxtKGyrbnXzJI9zKFCETVPz MmLVNlgzOTF3N{O=
K562 MnHrR4VtdCC4aXHibYxqfHliYYPzZZk> NHrKWGI4OiCq MXfuc5Qh[3m2b4TvfIlkKHSxIH7vck1OVSClZXzsJIxqdmW|IH;yJHBDVUO| M3;3ZlI5OjFzNUez
PBMCs NE\K[GhE\WyuII\pZYJqdGm2eTDhd5NigQ>? Mn7IO|IhcA>? Mlvyco91KGO7dH;0c5hq[yC2bzDuc44uVU1iY3XscEBtcW6nczDvdkBRSk2Fcx?= NUDZU2x[Ojh{MUG1O|M>

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Immunofluorescence
Nrf2; 

PubMed: 29794115     


Confocal microscopy of RAW264.7 stimulated or not with GW4869 (2 h).

29794115
In vivo Systemic administration of GW4869 does not alter the ceramide or sphingomylein content of liver, heart or skeletal muscle but does decrease the ceramide content and increase the sphingomyelin content in brain. Inhibition of nSMase2 with GW4869 slowed learning. Mice administered GW4869 do not progressively decrease latency to locate the hidden platform with repeated training trials, suggesting that they has difficulty learning to use spatial cues to navigate the pool[2]. Intraperitoneal injection of GW4869 reduces the levels of brain and serum exosomes, brain ceramide, and Aβ1-42 plaque load. GW4869 reduces amyloid plaque formation in vivo by preventing exosome secretion. GW4869 may have a low toxicity at levels needed to achieve a biological effect from nSMase2 inhibition[3].

Protocol

Cell Research:

[1]
- Collapse
  • Cell lines: MCF7 cells
  • Concentrations: 10-20 μM
  • Incubation Time: 30 min
  • Method:

    MCF7 human breast cancer cells are routinely cultured in RPMI 1640 containing 10% FBS at 37 °C in 5% CO2. Unless otherwise indicated, for treatment, cells are seeded at 1.7 × 106 cells/10-cm culture dish in 10 ml of complete medium; after 24 h, the medium is replaced with 7 ml of RPMI 1640 containing 2% FBS and 25 mM Hepes, pH 7.5, and the cells are rested for 2 h prior to treatment. GW4869 is routinely stored at −80 °C as a 1.5 mM stock suspension in Me2SO. Right before use, the suspension is solubilized by the addition of 5% methane sulfonic acid (MSA) (2.5 μl of 5% MSA in sterile double-distilled H2O are added to 50 μl of GW4869 stock suspension; therefore, the concentration of the GW4869 stock solution at the time of the experiments is 1.43 mM). The suspension is mixed and warmed up at 37 °C until clear. Cells are preincubated with the inhibitor for 30 min prior to treatment with TNF. Control cells are treated with Me2SO containing 5% MSA, similarly to the samples receiving the GW4869 solution. When different doses of GW4869 are tested, amounts of vehicle solution are added in order to equal the volume of GW4869 used for the highest dose.


    (Only for Reference)
Animal Research:

[2]
- Collapse
  • Animal Models: Mice with a complete loss of nSMase2 activity (background: C57BL/6J mice)
  • Dosages: 1.25 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO Insoluble . Please powderise before use.
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 577.5
Formula

C30H28N6O2.2HCl.XH2O
CAS No. 6823-69-4
Storage powder
in solvent
Synonyms GW69A, GW554869A

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID