ChemicalBook CAS DataBase List 438542-15-5

438542-15-5

Name	GW274150 phosphate
CAS	438542-15-5
Molecular Formula	C8H20N3O6PS
MDL Number	MFCD32690093
Molecular Weight	317.3
MOL File	438542-15-5.mol

Chemical Properties

storage temp.	Store at -20°C
form	Solid
color	White to off-white
Water Solubility	Water: 100 mg/mL (315.16 mM)

Hazard Information

Uses

GW274150 phosphate is a potent, selective, orally active and NADPH-dependent inhibitor of human inducible nitric oxide synthase (iNOS) (IC50=2.19 μM; Kd=40 nM) and rat iNOS (ED50=1.15 μM). GW274150 phosphate displays less potency for both humans or rats endothelial NOS (eNOS) and neuronal NOS (nNOS). GW274150 phosphate exerts a protective role in an acute model of lung injury inflammation[1][2].

in vivo

GW274150 phosphate is a long-acting (5 h half‐life in rats) iNOS inhibitor and is able to inhibit LPS‐mediated increase in plasma NO2^-, NO3^- levels 14 h after single intraperitoneal dose (ED₅₀=3 mg/kg)^[2].GW274150 phosphate (intraperitoneal injection; 2.5, 5, and 10 mg/kg; before carrageenan injection) reduces the degree of lung injury induced by carrageenan in a dose-related fashion. Oedema formation and PMNs infiltration in the pleural cavity are also significantly attenuated in a dose‐related manner in rats^[2].GW274150 phosphate (oral adminstration; 30 mg/kg; twice daily; 7 days) leads to significant neuroprotection, however, it displays a bell-shaped neuroprotective profile, being ineffective at high doses in 6-OHDA rat model of Parkinson disease (PD)^[3].

Animal Model:	SD rat^[2]
Dosage:	2.5, 5 and 10 mg/kg
Administration:	Intraperitoneal injection 5 min before carrageenan injection
Result:	Exerted a protective role in an acute model of inflammation, carrageenan-induced lung injury.

IC 50

iNOS

References

[1] Alderton WK, et al. GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo.Br J Pharmacol. 2005 Jun;145(3):301-12. DOI:10.1038/sj.bjp.0706168
[2] Dugo L, et al. Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. Br J Pharmacol. 2004 Mar;141(6):979-87. Epub 2004 Feb DOI:10.1038/sj.bjp.0705683
[3] Broom L, et al. Neuroprotection?by the?selective?iNOS?inhibitor?GW274150?in a?model?of?Parkinson?disease.Free Radic Biol Med.?2011 Mar 1;50(5):633-40. DOI:10.1016/j.freeradbiomed.2010.12.026

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