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The Cayman PPARγ-PAK contains a combination of frequently used ligands for the nuclear PPARγ. Each kit contains Ciglitazone, the first characterized member of the thiazolidinedione (TZD) class that binds to the PPARγ ligand-binding domain with an EC50 value of 3.0 µM.1,2 Rosiglitazone, a key reference TZD also called BRL 49653, is another PPARγ agonist provided. Also included is Troglitazone (Resulin™), another TZD; it was withdrawn from human therapeutic use due to hepatotoxicity.3 Also in this assortment is 15-deoxy-Δ12,14-Prostaglandin J2, a potent PPARγ ligand derived from PGD2. The actions of all of these compounds can be antagonized by the selective PPARγ antagonist, GW 9662,4 which is also in the kit.
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1
Willson, T.M., Cobb, J.E., Cowan, D.J., et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem 39 665-668 (1996).
2
Sohda, T., Mizuno, K., Imaniya, E., et al. Studies on antidiabetic agents. II. Synthesis of 5-[4-(1-methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione (ADD-3878) and its derivatives. Chem Pharm Bull 30(10) 3580-3600 (1982).
3
Kodera, Y., Takeyama, K., Murayama, A., et al. Ligand type-specific interactions of peroxisome proliferator-activated receptor γ with transcriptional coactivators. J Biol Chem 275 33201-33204 (2000).
4
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).
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