GW274150 phosphate

• CAT Number: I016430
• CAS Number: 438542-15-5
• Molecular Formula: C8H20N3O6PS
• Molecular Weight: 317.30
• Purity: ≥95%
• Synonyms: (2S)-2-amino-4-[2-(1-aminoethylideneamino)ethylsulfanyl]butanoic acid;phosphoric acid
• InChI: InChI=1S/C8H17N3O2S.H3O4P/c1-6(9)11-3-5-14-4-2-7(10)8(12)13;1-5(2,3)4/h7H,2-5,10H2,1H3,(H2,9,11)(H,12,13);(H3,1,2,3,4)/t7-;/m0./s1
• InChIKey: CNNHVSBCHOIDCA-FJXQXJEOSA-N
• SMILES: CC(=NCCSCCC(C(=O)O)N)N.OP(=O)(O)O

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].
GW274150 phosphate inhibits intracellular iNOS in J774 cells in a time-dependent manner, reaching IC50?values of 0.2±0.04 μM[1].GW274150?is >260-fold and 219-fold selective for iNOS against eNOS and nNOS in rat tissues, respectively. And it displays >100-fold and >80-fold for human iNOS against human eNOS and nNOS, respectively[1].
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].

Reference

[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.
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[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
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[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.
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