The transcription factor peroxisome proliferator-activated receptor δ (PPARδ) is a member of the superfamily of nuclear hormone receptors and is implicated both in lipid metabolism and in the regulation of genes with potential roles in neurotoxicity. GW 0742 is a selective PPARδ agonist (EC50 = 1.1 nM) that exhibits 1,000-fold selectivity over the other human PPAR subtypes.1 GW 0742 exhibits time-dependent neuroprotection in low KCl-induced apoptosis in cerebellar granule neuronal cultures. Despite the neuroprotective properties observed, prolonged (48h) incubation with GW 0742 produced significant inherent toxicity. This cell death was determined to be apoptotic as identified with the TUNEL assay.2
1
Sznaidman, M.L., Haffner, C.D., Maloney, P.R., et al. Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)-synthesis and biological activity. Bioorg Med Chem Lett131517-1521(2003).
2
Smith, S.A., Monteith, G.R., Robinson, J.A., et al. Effect of the peroxisome proliferator-activated receptorβ activator GW0742 in rat cultured cerebellar granule neurons. J Neurosci Res77240-249(2004).
Sznaidman, M.L., Haffner, C.D., Maloney, P.R., et al. Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)-synthesis and biological activity. Bioorg Med Chem Lett131517-1521(2003).
Smith, S.A., Monteith, G.R., Robinson, J.A., et al. Effect of the peroxisome proliferator-activated receptorβ activator GW0742 in rat cultured cerebellar granule neurons. J Neurosci Res77240-249(2004).
GW 0742 is available in the following screening
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