MSDC-0602K

MSDC-0602K (Azemiglitazone potassium), a PPARγ-sparing thiazolidinedione (Ps-TZD), binds to PPARγ with the IC50 of 18.25 μM[1]. MSDC-0602K modulates the mitochondrial pyruvate carrier (MPC). MSDC-0602K can be used for the research of fatty liver including dysfunctional lipid metabolism, inflammation, and insulin resistance[2]. MSDC-0602K, an insulin sensitizer, improves insulinemia and fatty liver disease in mice, alone and in combination with Liraglutide[3].

Signaling Pathways >> Cell Cycle/DNA Damage >> PPAR

Research Areas >> Metabolic Disease

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Insulin Receptor

PPAR-γ:18.25 μM (IC50)

Diabetic db/db and MS-NASH mice are treated with MSDC-0602K by oral gavage, Liraglutide by s.c. injection, or combination MSDC-0602K + Liraglutide. This combination treatment may be an effective therapeutic strategy for diabetes and non-alcoholic steatohepatitis (NASH). Animal Model: Five-week-old male db/db mice on C57BL/6J background and age/sex-matched db/+ control mice[1] Dosage: 30 mg/kg MSDC-0602K; 0.2 mg/kg Liraglutide (obtained from MedChemExpress; HY-P0014) Administration: MSDC-0602K gavage daily, Liraglutide s.c. injection every other day, or combined MSDC-0602K+ Liraglutide Result: MSDC-0602K corrected glycemia and reduced insulinemia when given alone, or in combination with Liraglutide. However, MSDC-0602K + Liraglutide combination more significantly improved glucose tolerance and liver histology.

[1]. Zhouji Chen, et al. Insulin resistance and metabolic derangements in obese mice are ameliorated by a novel peroxisome proliferator-activated receptor γ-sparing thiazolidinedione. J Biol Chem. 2012 Jul 6;287(28):23537-48.

[2]. Jerry R Colca, et al. MSDC-0602K, a metabolic modulator directed at the core pathology of non-alcoholic steatohepatitis. Expert Opin Investig Drugs. 2018 Jul;27(7):631-636.

[3]. Dakota R Kamm, et al. Novel insulin sensitizer MSDC-0602K improves insulinemia and fatty liver disease in mice, alone and in combination with liraglutide. J Biol Chem. Jan-Jun 2021;296:100807.