GW 9662

A PPARγ antagonist

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

276.7

≥98%

O=C(C1=CC([N+]([O-])=O)=CC=C1Cl)N([H])C2=CC=CC=C2

C13H9ClN2O3

22978-25-2

≥ 4 years

DMF: 35 mg/ml DMF:PBS (7.2 pH) (1:2): 0.5 mg/ml DMSO: 33 mg/ml Ethanol: 2 mg/ml

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.Maxey, K.M.,Hessler, E.,MacDonald, J., et al. The nature and composition of 15-deoxy-Δ^12,14-PGJ₂. Prostaglandins & Other Lipid Mediators 62, 15-21 (2000).
3.Wright, H.M.,Clish, C.B.,Mikami, T., et al. A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation. The Journal of Biological Chemisty 275, 1873-1877 (2000).
4.Lehmann, J.M.,Moore, L.B.,Smith-Oliver, T.A., et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J. Biol. Chem. 270, 12953-12956 (1995).
5.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).
6.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. The Journal of Biological Chemisty 276, 16015-16023 (2001).
7.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. Proceedings of the National Academy of Sciences of the United States of America 98, 2443-2448 (2001).