MSDC-0160 is a prototype mTOR-modulating insulin sensitizer being studied to treat diabetes and Alzheimer's disease. 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[3]. 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[4].
MSDC 0160/米格列酮 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CML CD34+CD38- cells
50 μM
24 hours
MSDC-0160 inhibited glucose oxidation in the primitive CD34+CD38- population
Nat Commun. 2023 Aug 17;14(1):4634
CML CD34+ cells
20 μM and 100 μM
24 hours
MSDC-0160 reduced glucose contribution to TCA cycle metabolites in a dose-dependent manner
Nat Commun. 2023 Aug 17;14(1):4634
human islet cells
1-50 μM
24 hours
To evaluate the effects of MSDC-0160 on restoring insulin/IGF-1 sensitivity and insulin content in human β-cells. Results showed that MSDC-0160 treatment increased AMPK activity, reduced mTOR activity, restored IGF-1-induced phosphorylation of Akt and GSK-3, and increased Pdx1 protein expression.
PLoS One. 2013 May 1;8(5):e62012
Human retinal endothelial cells (HRECs)
1 μM and 10 μM
MSDC-0160 (MPC inhibitor) did not significantly affect HREC barrier function or cell spreading behavior.
J Biol Chem. 2025 May;301(5):108472
MSDC 0160/米格列酮 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice, rats, and cynomolgus monkeys
Oral
50, 100, or 150 mg
Once daily for 12 weeks
To evaluate the efficacy and safety of MSDC-0160 in patients with type 2 diabetes. Results showed that MSDC-0160 was comparable to pioglitazone in lowering fasting glucose and HbA1c levels, but with fewer side effects such as fluid retention and weight gain.
Clin Pharmacol Ther. 2013 Apr;93(4):352-9
Mice
Sciatic nerve transection model
Local administration
100 μM
1 day (24 hours)
To evaluate the effect of MSDC-0160 on ATP levels and Wallerian degeneration after sciatic nerve transection. Results showed that MSDC-0160 did not significantly alter ATP levels or promote Wallerian degeneration on the transection side.
eNeuro. 2023 Mar 20;10(3):ENEURO
Rats and mice
AAV αSyn overexpression model and PFF αSyn seeding model
Oral
30 mg/kg
Once daily for 4 months
To evaluate the effects of MSDC-0160 on αSyn aggregation. In the AAV αSyn overexpression model, MSDC-0160 increased αSyn aggregation; in the PFF seeding model, MSDC-0160 increased αSyn pathology burden at 5 weeks but showed no significant difference at 13 weeks.
Free Neuropathol. 2020;1:33
NRG-W41 mice
Patient-derived xenograft model
Oral gavage
30 mg/kg/day
Once daily for 4 weeks
Combination of MSDC-0160 with imatinib significantly reduced therapy-resistant CD34+CD38- CML cells
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