A literature search has found articles where in vitro cultured cells were treated with this product for up to 24 hours. Conducting a literature search may provide further guidance on long-term treatment.
D1692
GW4869
≥90% (NMR), powder, N-SMase inhibitor
Synonym(s):
N,N′-Bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3,3′-p-phenylene-bis-acrylamide dihydrochloride
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Product Name
GW4869, ≥90% (NMR)
Quality Level
Assay
≥90% (NMR)
form
powder
storage condition
desiccated
protect from light
color
light yellow to yellow
mp
>300 °C
solubility
DMSO: 0.2 mg/mL
originator
GlaxoSmithKline
storage temp.
2-8°C
SMILES string
Cl.Cl.O=C(Nc1ccc(cc1)C2=NCCN2)\C=C/c3ccc(\C=C/C(=O)Nc4ccc(cc4)C5=NCCN5)cc3
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-LOLTXFFGSA-N
General description
GW4869 is a commonly used pharmacological agent, which inhibits exosome generation. It blocks ceramide-mediated inward budding of multivesicular bodies (MVBs) and the release of mature exosomes from MVBs.[1] GW4869 exhibits cytotoxicity to phosphatidylserine-expressing myeloma cells.[2] It inhibits the secretion of IFN (interferon)-α by plasmacytoid dendritic cells (pDCs).[3]
Application
GW4869 has been used:
- as an inhibitor of neutral sphingomyelinase and exosome biogenesis[4][5][6]
- to analyse the effects of arsenic trioxide (ATO) treatment for hepatoma carcinoma HCCLM3 cells on ceramide production[7]
- to determine the contributions of p75 neurotrophin receptor (p75NTR) and tropomyosin receptor kinase A (TrkA)- coupled pathways to nerve growth factor (NGF)-induced thermal hypersensitivity in rats[8]
Biochem/physiol Actions
A cell-permeable, potent, specific, non-competitive inhibitor of N-SMase (neutral sphingomyelinase)
Features and Benefits
This compound was developed by GlaxoSmithKline. To browse the list of other pharma-developed compounds and Approved Drugs/Drug Candidates, click here.
Storage Class Code
11 - Combustible Solids
WGK
WGK 3
Flash Point(F)
Not applicable
Flash Point(C)
Not applicable
Personal Protective Equipment
dust mask type N95 (US), Eyeshields, Gloves
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Li Chen et al.
FEBS letters, 590(23), 4263-4274 (2016-10-25)
Exosomes mediate intercellular microRNA delivery between hepatic stellate cells (HSC), the principal fibrosis-producing cells in the liver. The purpose of this study was to identify receptors on HSC for HSC-derived exosomes, which bind to HSC rather than to hepatocytes. Our
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Cell discovery, 4, 19-19 (2018-05-01)
Zika virus (ZIKV) is a neurotrophic flavivirus that is capable of infecting humans, leading to brain abnormalities during fetal development. The ZIKV infectivity in neural target cells remains poorly understood. Here, we found that ZIKV specifically infected glial fibrillary acidic
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Rashed MH, et al.
Oncotarget, 8(12), 20145-20145 (2017)
Elevated Wall Tension Leads to Reduced miR-133a in the Thoracic Aorta by Exosome Release
Akerman AW, et al.
Journal of the American Heart Association, 8(1), e010332-e010332 (2019)
Phillip B Munson et al.
Scientific reports, 9(1), 11688-11688 (2019-08-14)
Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that
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Can in vitro cultured cells be treated longterm with GW4869? (for example 10 days treatment)
1 answer-
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After resuspending 5 mg GW4869 from Millipore D1692 in DMSO, should it still be stored at 4°C?
1 answer-
GW4869 has a maximum solubility of 0.2 mg/mL in DMSO. It is hygroscopic and light-sensitive, so solutions of GW4869 should be stored as single-use aliquots. When stored at -20 degrees C, stock solutions should be stable for at least 3 months.
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