GW4869

GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor with an IC50 of 1 μM. GW4869 is an inhibitor of exosome biogenesis/release.

Product information

CAS Number: 6823-69-4

Molecular Weight: 577.50

Formula: C30H30Cl2N6O2

Chemical Name: (2E)-N-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3-{4-[(1E)-2-{[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]carbamoyl}eth-1-en-1-yl]phenyl}prop-2-enamide dihydrochloride

Smiles: Cl.Cl.O=C(/C=C/C1C=CC(/C=C/C(=O)NC2C=CC(=CC=2)C2NCCN=2)=CC=1)NC1C=CC(=CC=1)C1NCCN=1

InChiKey: NSFKAZDTKIKLKT-CLEIDKRQSA-N

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+;;

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 0.1 mg/mL (0.17 mM; Need ultrasonic). H2O : < 0.1 mg/mL (ultrasonic) (insoluble).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

GW4869 (10 μM) partially inhibits TNF-induced sphingomyelin (SM) hydrolysis, and 20 μM of the compound is protected completely from the loss of SM. The addition of 10-20 μM GW4869 completely inhibits the initial accumulation of ceramide, whereas this effect is partially lost at later time points (24 h). The action of GW4869 occurs downstream of the drop in glutathione. GW4869 is able, in a dose-dependent manner, to significantly protect from cell death. GW4869 (10 or 20 μM) inhibits both exosome release and pro-inflammatory cytokine production in macrophages. GW4869 inhibits the ceramide-mediated inward budding of multivesicular bodies (MVBs) and release of mature exosomes from MVBs. GW4869 also could reverse the inhibition of CCN2 3’-UTR activity by miR-214-enriched exosomes in hepatic stellate cells. Solution Attention: GW4869 is routinely stored at −80 °C as a stock suspension in DMSO.

In Vivo:

GW4869 (2.5 μg/g, i.p.) causes inhibition of exosome release blocks LPS-stimulated pro-inflammatory cytokine production and cardiac inflammation in mice. GW4869 mitigates LPS-caused myocardial dysfunction and improves survival in mice. GW4869 (2.5 μg/g, i.p.) blocks the production of pro-inflammatory cytokines and cardiac inflammation in CLP mice.

Products are for research use only. Not for human use.