MSDC-0160

MSDC-0160 is a thiazolidinedione (TZD) with antidiabetic and neuroprotective activities.¹ It inactivates the mitochondrial pyruvate carrier (MPC; IC₅₀ = 1.2 µM) without affecting peroxisome proliferator-activated receptor γ (PPARγ; IC₅₀ = 31.65 µM) in vitro.² MSDC-0160 enhances the rate of insulin-stimulated lipogenesis in 3T3-L1 adipocytes in a dose-dependent manner.¹ Dietary administration of MSDC-0160 (100 mg/kg) lowers blood glucose levels in obese, hyperglycemic, hyperinsulinemic, and insulin-resistant KKAγ mice. MSDC-0160 prevents neurodegeneration in a C. elegans model of Parkinson's disease, an effect that is blocked by knockdown of the mammalian target of rapamycin (mTOR).² It also prevents overactivation of mTOR in the MPTP-induced and engrailed heterozygous (En^+/-) mouse models of Parkinson's disease.

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1. Tanis, S.P., Parker, T.T., Colca, J.R., et al. Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone. J. Med. Chem. 39(26), 5053-5063 (1996).

2. Quansah, E., Peelaerts, W., Langston, J.W., et al. Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. Mol. Neurodegener. 13(1), 28 (2018).