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. Rosiglitazone (BRL 49653) is a prototypical thiazolidinedione and has served as a reference compound for this class. There are many PPARγ agonists, including 15-deoxy-Δ12,14-prostaglandin J2 and azelaoyl PAF, which are naturally derived. However, only a few antagonists have been reported. GW 9662 blocks the PPARγ-induced differentiation of monocytes to osteoclasts by >90% at a dose of 0.1 μM. It is therefore a much more potent antagonist than BADGE, which is another reported PPARγ antagonist.
