835619-41-5

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^[1].