Indeglitazar (PPM 204) is an orally available PPAR pan-agonist for all three PPARα , PPARδ and PPARγ
In Vitro
In an assay of preadipocyte differentiation, measuring in part functional insulin sensitization capability of the cells, Indeglitazar shows an EC 50 of 0.32 μM compared with Rosiglitazone, which shows an EC 50 of 13 nM, although the maximal response obtained from the 2 compounds is comparable. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
An initial assessment of in vivo activity is carried out using the Zucker rat model of diabetes. The significant lowering of glucose, HbA 1C , triglycerides, and total cholesterol are observed after i.v. treatment with 10 mg/kg Indeglitazar once per day for 3 weeks. Notably, the level of Adiponectin (on day 21) is essentially unchanged in treated vs. untreated animals (4.8 mcg/mL vs. 4.9 mcg/mL), thus the observed reductions in glucose and HbA 1C are achieved in an adiponectin-independent fashion. These differences in the effects of Indeglitazar in vivo may be a consequence of synergy between the 3 PPAR activities or because of the SPPARM profile of the compound, or a combination of these factors. The oral activity of Indeglitazar is assessed in the ob/ob model of diabetes and insulin resistance. Indeglitazar significantly decreases glucose, insulin, triglycerides, and free fatty acid levels . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
