A cell-permeable pyridylsulfone that acts as a selective, high affinity PPARb (PPARd) ligand (IC50 in PPAR ligand displacement assays =200nM against human PPARb and >10uM against PPARa or PPARg) and effectively antagonizes agonist-induced, but not basal, PPARb transcription activity both in cultures in vitro (IC50=126nM in CV-1 cells) and in mice in vivo (82% and 71% inhibition of 10mg/kg GW0742-induced Adr and Angptl4 mRNA upregulation, respectively, in colon epithelium; 10mg/kg GSK3787; p.o.) by covalently modifying PPARb at Cys249. GSK3787 is also shown to exhibit weak agonistic activity toward PPARg (1.2-fold increase above basal level by 1uM GSK3787), and effectively block the more potent agonist GW1929 from further stimulation (1.5 and 3.5-fold above basal by 0.3uM GW1929 in the presence or absence of 1uM GSK3787, respectively).
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
