MSDC-0602, a PPARγ-sparing thiazolidinedione (TZD), interacts with the mitochondrial pyruvate carrier (MPC) and inhibits its activity and are effective for treatment of type 2 diabetes with reducing risk of PPARγ-mediated side effects[1][2].
Azemiglitazone, also known as MSDC-0602, is an orally active thiazolidinedione (TZD)-like molecule with low binding and activation affinity for PPARγ. Azemiglitazone inhibits the mitochondrial pyruvate carrier (MPC), thereby inhibiting Alzheimer's disease and attenuating non-alcoholic steatohepatitis (NASH)-induced liver injury[4][5].At a concentration of 15 μM for 4 hours, Azemiglitazone cross-links specifically with MPC and inhibits pyruvate oxidation and glucose production in hepatic mitochondria by interacting with MPC2[3].Azemiglitazone has a low binding and activation affinity for PPARγ, with an IC50 of 18.25 μM[6].
Azemiglitazone 动物研究
Animal study
Azemiglitazone (2-5 μM in blood, p.o for 2-4 weeks) improves insulin sensitivity in the striated muscle, adipose tissue and liver of DIO C57BL/6 mice[6].Azemiglitazone reduced NASH-induced liver injury and prevented and reversed stellate cell activation and fibrosis in HTF-C diet-fed C57BL6/J mice (2-5 μM in blood, p.o. for weeks 12 and 3, respectively)[4].
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