MSDC-0160

A new generation insulin sensitizer and mitochondrial target of thiazolidinediones (mTOT) modulator that has low affinity for binding and activation of PPARγ (EC50=23.7 uM) and shows insulin-sensitizing effects in mouse models of diabetes; increases AMPK activity and reduces mTOR activity, maintains β-cell phenotype in human islets.Diabetes Phase 2 Clinical (In Vitro) :MSDC 0160 (Mitoglitazone; 1-50 μM; for 24 hours) significantly decreases phosphorylation of mTOR at 20 and 50 μM.MSDC 0160 acts as insulin sensitizers without activating PPARγ.MSDC 0160 (10 μM; pretreatment 1 hour) prevents the MPP+ (10 μM) -induced loss of both tyrosine hydroxylase (TH) -immunoreactive differentiated Lund human mesencephalic (LUHMES) cells.MSDC 0160 (10 or 100 μM) prevents the loss of GFP-fluorescent dopaminergic neurons induced by MPP+ (0.75 mM) in nematodes.MSDC 0160 (10-20 μM) in conbination with IGF-1 prevents the loss of insulin content and maintains insulin secretion.MSDC 0160 (1-50 μM) treatment maintains human β-cell phenotype. (In Vivo) :MSDC 0160 (Mitoglitazone; 30 mg/kg; oral gavage; daily; for 7 days) improves locomotor behavior, increases survival of nigral dopaminergic neurons, boosts striatal dopamine levels, and reduces neuroinflammation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treated mice.