Results. A series of compounds (1b− 11) was chosen from the literature that had been previously tested in rodent models of diabetes. 4, 7, 9-11 Clofibric acid (1b), the active form of clofibrate (1a), 15 was purchased from Sigma. Compounds 2− 11 were synthesized by the literature methods. 7, 9-11 The compounds were tested in a transient transfection assay in CV-1 cells for their ability to activate PPARs. To allow comparison of the relative transcriptional activity of the three receptors on the same target gene and to prevent endogenous receptors from complicating the interpretation of results, an established receptor chimera system was used. 14 The ligand binding domains of mouse PPARα, PPARγ, and PPARδ were each fused to the DNA-binding domain of the yeast transcription factor GAL4. CV-1 cells were transiently transfected with expression vectors for the respective PPAR chimera together with a reporter construct containing five copies of the GAL4 upstream activator element driving expression of secreted placental alkaline phosphatase (SPAP). Weak activity on PPARα was observed for only 1b and 2, and no activity was seen on PPARδ for any of the compounds (Table 1). By contrast, it was found that all the compounds (1b− 11) were efficacious activators of PPARγ, showing 25− 30-fold induction of reporter gene activity at the highest dose tested (data not shown). The potency of compounds 1b− 11 as judged by the EC 50 for PPARγ activity, was structure dependent and spanned a wide dose range from millimolar (for 1b) to nanomolar (for 10).