GW274150_DataSheet_MedChemExpress
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Inhibitors, Agonists, Screening Librarieswww.MedChemExpress.comData SheetBIOLOGICAL ACTIVITY: GW274150 is a novel arginine–competitive, NADPH–dependent iNOS inhibitor that has been identified from a series of acetamideamino acids that have a high selectivity for iNOS vs both eNOS (> 260–fold) and nNOS (> 219–fold) and high bioavailability (> 90%)after oral administration.Target: iNOSin vivo: GW274150 demonstrates a narrow neuroprotective therapeutic window against the toxic actions of 6–OHDA. GW274150administration leads to a dose–dependent decrease in the number of iNOS–positive cells in the SNc of the 6–OHDA–lesioned animals.The iNOS inhibitor GW274150 fails to produce long–term neuroprotection after its withdrawal in the 6–OHDA–lesioned rat. [1]PROTOCOL (Extracted from published papers and Only for reference) Animal administration [1]Male Sprague–Dawley rats (220–260 g on the day of surgery) were housed three rats per cage. For the first study, groups of animals (n= 6) were treated with either the iNOS inhibitor GW274150 (3, 10, and 30 mg/kg) or drug vehicle (distilled water) administered orallytwice daily for 7 consecutive days starting from day 2 after 6–OHDA lesion induction. Dose selection was based on efficacious dosesdetermined previously in pain models for effectively inhibiting iNOS. The half–life of GW274150 was 6 h. The time point for theinitiation of drug administration, being 2 days after 6–OHDA administration, was determined from previous studies in which we clearlyobserved the start of a significant increase in the inflammatory response in the 6–OHDA model of PD; however, at this stage noneuronal loss is observed but the neurons are traumatized. A 7–day dosing regimen starting 2 days after 6–OHDA lesioning waschosen because this covered the onset and peak of inflammation observed in the 6–OHDA model and covers the period when themajority of neurons are lost. Animals were sacrificed after the final day of drug treatment (day 9 after lesioning). In a second study,drug treatment after 6–OHDA lesioning with the iNOS inhibitor GW274150 (10 mg/kg) was performed as before for 7 days, but theanimals were sacrificed after a further 7–day washout period after the final day of iNOS treatment. This second study was terminatedon day 16 post–6–OHDA lesioning and was performed to examine whether the neuroprotective effects of iNOS inhibition were longlasting.References: [1]. 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.[2]. Seymour M, et al. Ultrasonographic measures of synovitis in an early phase clinical trial: a double–blind, randomised, placebo and comparator controlledphase IIa trial of GW274150 (a selective inducible nitric oxide synthase inhibitor) in rheumatoid arthritis. Clin Exp Rheumatol. 2012 Mar–Apr;30(2):254–61.Product Name:GW274150Cat. No.:HY-12119CAS No.:210354-22-6Molecular Formula:C8H17N3O2SMolecular Weight:219.30Target:OthersPathway:OthersSolubility:H2O: ≥ 62 mg/mL
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