The peroxisome proliferator-activated receptor-γ (PPARγ) is the nuclear receptor responsible for transducing the therapeutic activity of the thiazolidinediones (TZDs), a group of structurally related synthetic agonists with antidiabetic actions in vivo.^1,2 Rosiglitazone (BRL49653) is a prototypical TZD and has served as a reference compound for this class.³ MCC-555 is a structural homolog of rosiglitazone and the other TZDs. MCC-555 binds with about 1/10 the affinity of rosiglitazone to PPARγ.⁴ Despite this, MCC-555 is a more potent antidiabetic agent in whole animal experiments than rosiglitazone and several other prototypic TZDs; the ED₅₀ value in these experiments was 2.7 mg/kg for MCC-555 compared with 7.1 mg/kg for rosiglitazone. MCC-555 is therefore a unique new member of the TZD class and may be useful in differentiating some of the multiple activities attributed to this class of compounds.

≥98%