The peroxisome proliferator-activated receptor γ (PPARγ) is the nuclear receptor responsible for transducing the therapeutic activity of the thiazolidinediones. Thiazolidinediones are a group of structurally related synthetic PPARγ agonists with antidiabetic actions in vivo.1,2 Rosiglitazone (BRL 49653) is a prototypical thiazolidinedione and has served as a reference compound for this class.3 There are many PPARγ agonists, including 15-deoxy-Δ12,14-prostaglandin J2 and azelaoyl PAF, which are naturally derived.4,5 However, only a few antagonists have been reported.6 GW 9662 blocks the PPARγ-induced differentiation of monocytes to osteoclasts by >90% at a dose of 0.1 µM.6 It is therefore a much more potent antagonist than BADGE, which is another reported PPARγ antagonist.7
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Cantello, B.C.C., Cawthorne, M.A., Cottam, G.P., et al. [[ω-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents. J Med Chem 37 3977-3985 (1994).
Davies, S.S., Pontsler, A.V., Marathe, G.K., et al. Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor γ ligands and agonists. J Biol Chem 276 16015-16023 (2001).
Bendixen, A.C., Shevde, N.K., Dienger, K.M., et al. IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor γ1. Proc Natl Acad Sci USA 98 2443-2448 (2001).