Azemiglitazone

Azemiglitazone (MSDC-0602) is an orally active thiazolidinedione (TZD) -like molecule, which binds to PPARγ with low binding and activating affinity. Azemiglitazone inhibits mitochondrial pyruvate carrier (MPC), which inhibits Alzheimer’s disease and diminishes nonalcoholic steatohepatitis (NASH) caused liver injury^[4][5]. In Vitro:Azemiglitazone (15 μM, 4 h) crosslinks specifically to MPC, inhibits pyruvate oxidation and glucose production in liver mitochondria with interaction with MPC2^[3].
Azemiglitazone has low binding and activating affinity for PPARγ with IC₅₀ of 18.25 μM^[6]. In Vivo:Azemiglitazone (2-5 μM in blood, p.o for 2-4 weeks) improves insulin sensitivity in striated muscle, adipose tissue, and liver of DIO C57BL/6 mice^[6].
Azemiglitazone (2-5 μM in blood, p.o for 2-4 weeks) improves mitochondrial respiratory rate in DIO C57BL/6 mice^[6]. Azemiglitazone reduces NASH caused liver injury, prevents (2-5 μM in blood, p.o. for 12 weeks) and reverses (2-5 μM in blood, p.o. for 3 weeks) stellate cells activation and fibrosis in HTF-C diet feeding C57BL6/J mice^[4].
Azemiglitazone (2-5 μM in blood, p.o.) causes weight loss and suppresses stellate cell activation with or without MPC function in HTF-C diet feeding LS-Mpc^2-/-C57BL6/J mice^[4].