GW 9662-d5

Internal standard for the quantification of GW 9662

The peroxisome proliferator-activated receptor γ (PPARγ) is the nuclear receptor responsible for transducing the therapeutic activity of the thiazolidinediones (TZDs). TZDs are a group of structurally related synthetic PPARγ agonists with antidiabetic actions in vivo.1,2 Rosiglitazone is a prototypical TZD 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.7 It is therefore a much more potent antagonist than BADGE, which is another reported PPARγ antagonist.7

281.7

≥99% deuterated forms (d1-d5)

ClC1=CC=C([N+]([O-])=O)C=C1C(NC2=C([2H])C([2H])=C([2H])C([2H])=C2[2H])=O

C13H4ClD5N2O3

≥ 4 years

DMF: 35 mg/ml DMF:PBS(pH7.2) (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).