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GW4869

Name: GW4869
Brand: Selleck Chemicals
SKU: S7609
Rating: 5 (30 reviews)

Catalog No.S7609 Synonyms: GW69A, GW554869A

For research use only.

GW4869 (GW69A, GW554869A) 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, also is a commonly used exosome inhibitor.

CAS No. 6823-69-4

Selleck's GW4869 has been cited by 30 publications

Purity & Quality Control

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Phospholipase (e.g. PLA) Signaling Pathways

Phospholipase (e.g. PLA) Signaling Pathway Map

Biological Activity

Description

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	M1nQW2Z2dmO2aX;uJIF{e2G7	NInLfWEyOC1{MDFOwG0>		M1vWUpRp\SCjZHTpeIlwdiCxZjCxNEDPxE1iR2e0PFY6KHOrZ37p[olk[W62bImgbY5pcWKrdHXkJHRPTi2rbnT1Z4VlKFOPIHj5[JJwdHm\|aYOsJJdp\XKnYYOgNlAh\|ryPIH;mJJRp\SClb33wc5Vv\CCycn;0[YN1\WRiY3;tdIxmfGWueTDmdo9uKHSqZTDsc5N{KG:oIIPwbIlv\2:veXXsbY4>	Mk\zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTJzNUSwPVgoRjF{MUW0NFk5RC:jPh?=
OPM2	MlzvVJJwdGmoZYLheIlwdiCjc4PhfS=>	NVHHTHVCOCxiMT6yOUwhOi53LDC1MEAyOCxiMkCsJFQxKM7:bX;sM2w>	M2PD[lI1KGh?	Mn;xeIhmKGOnbHygdJJwdGmoZYLheIlwdiC{YYTlJJdieyCrbnPy[YF{\WRiYX\0[ZIhT1d2OE[5JJRz\WG2bXXueE4hXGinIHnubIljcXSrb36gc4Yh[2WubDDwdo9tcW[ncnH0bY9vKHejczDvcox6KHOrZ37p[olk[W62IIfo[Y4hfGinIHPvcoNmdnS{YYTpc44hd2ZiR2e0PFY6KHejczC0NEDPxG2xbD;MJI9zKGirZ3jldk4>	M3vJS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEW4Nlk1Lz5{OEi1PFI6PDxxYU6=
RPMI-8226	NFjQW4tE\WyuII\pZYJqdGm2eTDhd5NigQ>?		MV[3NkBp	M4\JfoN6fG:2b4jpZ{B1dyCjIIDhcoVtKG:oIF3NJINmdGxibHnu[ZM>	M1vN[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkGxOVc{Lz5{OEKxNVU4OzxxYU6=
NCI-H929	MV\D[YxtKH[rYXLpcIl1gSCjc4PhfS=>		MXG3NkBp	NWXucIFZ[3m2b4TvfIlkKHSxIHGgdIFv\Wxib3[gUW0h[2WubDDsbY5mew>?	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDJzMUW3N{c,Ojh{MUG1O\|M9N2F-
JJN3	NWXUbIRWS2WubDD2bYFjcWyrdImgZZN{[Xl?		MlfhO\|IhcA>?	MX7jfZRwfG:6aXOgeI8h[SCyYX7lcEBw\iCPTTDj[YxtKGyrbnXz	MmHVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh{MUG1O\|MoRjJ6MkGxOVc{RC:jPh?=
U266	NUTST\|NCS2WubDD2bYFjcWyrdImgZZN{[Xl?		MkPYO\|IhcA>?	MlnMZ5l1d3SxeHnjJJRwKGFicHHu[Ywhd2ZiTV2gZ4VtdCCuaX7ldy=>	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDJzMUW3N{c,Ojh{MUG1O\|M9N2F-
Daudi	NHf0OmxE\WyuII\pZYJqdGm2eTDhd5NigQ>?		MmLpO\|IhcA>?	MkX3co91KGO7dH;0c5hq[yC2bzDuc44uVU1iY3XscEBtcW6nczDvdkBRSk2Fcx?=	M2TJZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkGxOVc{Lz5{OEKxNVU4OzxxYU6=
Jurkat	NHvRNXRE\WyuII\pZYJqdGm2eTDhd5NigQ>?		M1LLeFczKGh?	MnPNco91KGO7dH;0c5hq[yC2bzDuc44uVU1iY3XscEBtcW6nczDvdkBRSk2Fcx?=	M2PPWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkGxOVc{Lz5{OEKxNVU4OzxxYU6=
K562	NGHGOJdE\WyuII\pZYJqdGm2eTDhd5NigQ>?		NVvj[VJ[PzJiaB?=	MmTlco91KGO7dH;0c5hq[yC2bzDuc44uVU1iY3XscEBtcW6nczDvdkBRSk2Fcx?=	NFLDZXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEKxNVU4Oyd-MkiyNVE2PzN:L3G+
PBMCs	MVXD[YxtKH[rYXLpcIl1gSCjc4PhfS=>		NUjXN5l[PzJiaB?=	NX3UN\|VQdm:2IHP5eI91d3irYzD0c{Bvd25vTV2gZ4VtdCCuaX7ld{BweiCSQl3Ddy=>	M{PiSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MkGxOVc{Lz5{OEKxNVU4OzxxYU6=

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Immunofluorescence

Nrf2

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 (from reference)

Cell Research:

^[1]

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.

Animal Research:

^[2]

Animal Models: Mice with a complete loss of nSMase2 activity (background: C57BL/6J mice)
Dosages: 1.25 mg/kg
Administration: i.p.

References

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	577.5
Formula	C₃₀H₂₈N₆O₂.₂HCl.XH₂O
CAS No.	6823-69-4
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
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=NCCN5.Cl.Cl

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In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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