6823-69-4 GW4869-web name

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上海芮珊医药

RESUPERPHARMTECH

Key words：API intermedate impurity

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Fine Chemical: Impurity ┆

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生物活性	GW4869 is a noncompetitive neutral sphingomyelinase (N-SMase) inhibitor with an IC₅₀ of 1 μM. GW4869 is an inhibitor of exosome biogenesis/release^[1]^[2]^[3]^[4].
IC₅₀ & Target	IC50: 1 μM (neutral sphingomyelinase)^[1]
体外研究 (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^[1]. 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^[2]. GW4869 also could reverse the inhibition of CCN2 3’-UTR activity by miR-214-enriched exosomes in hepatic stellate cells^[3]. Solution Attention: GW4869 is routinely stored at −80 °C as a stock suspension in DMSO. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability Assay^[1] Cell Line:MCF7 human breast cancer cells.Concentration:10-20 μM.Incubation Time:30 min (then treated with TNF (3 nM) followed).Result:Significantly inhibited TNF-induced SM hydrolysis, whereas 20 μM of the compound protected completely from the loss of SM.

体内研究 (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^[2]. GW4869 (2.5 μg/g, i.p.) blocks the production of pro-inflammatory cytokines and cardiac inflammation in CLP mice^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model:10-12 weeks old Male wild-type C57BL/6 mice (Endotoxin-Challenged Mice)[2].Dosage:2.5 μg/g.Administration:I.P. once (1 h later, followed by an i.p. injection of LPS (2.5 μg/g, 100 μL)).Result:Significantly decreased exosome levels by 37% in sera, compared to levels collected from control mice. At 12 h after LPS injection, the levels of circulating exosomes were increased significantly compared to PBS-controls, as evidenced by a 1.7-fold elevation in the AChE activity.

体内研究
(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^[2].
GW4869 (2.5 μg/g, i.p.) blocks the production of pro-inflammatory cytokines and cardiac inflammation in CLP mice^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:10-12 weeks old Male wild-type C57BL/6 mice (Endotoxin-Challenged Mice)[2].Dosage:2.5 μg/g.Administration:I.P. once (1 h later, followed by an i.p. injection of LPS (2.5 μg/g, 100 μL)).Result:Significantly decreased exosome levels by 37% in sera, compared to levels collected from control mice. At 12 h after LPS injection, the levels of circulating exosomes were increased significantly compared to PBS-controls, as evidenced by a 1.7-fold elevation in the AChE activity.

分子量	577.50
Formula	C₃₀H₃₀Cl₂N₆O₂
CAS 号	6823-69-4
运输条件	Room temperature in continental US; may vary elsewhere.
储存方式	4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性数据	In Vitro: DMSO : 0.1 mg/mL (0.17 mM; Need ultrasonic) 0.1 M HCL : < 1 mg/mL (ultrasonic;adjust pH to 2 with HCl) (insoluble) H₂O : < 0.1 mg/mL (ultrasonic) (insoluble) *GW4869 is usually formulated as a suspension.