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Data Sheet
Product Name:Cat. No.:CAS No.:
Molecular Formula:Molecular Weight:Target:Pathway:Solubility:
MSDC 0160HY-100550146062-49-9C19H18N2O4S370.42
Insulin Receptor
Protein Tyrosine Kinase/RTKDMSO: ≥ 30 mg/mL
BIOLOGICAL ACTIVITY:
MSDC 0160 act as an insulin sensitizer and a modulator of mitochondrial pyruvate carrier (MPC), a key controller of cellularmetabolism that influences mTOR (mammalian target of rapamycin) activation.
In Vitro: MSDC–0160 acts as insulin sensitizers without activating PPARγ. MSDC–0160 (10 μM) pretreatment (1 hour) prevents thecells. MSDC–0160 protects only TH–immunoreactive neurons, which is consistent with the selected concentration of MPP+
MPP+ (10 μM)–induced loss of both tyrosine hydroxylase (TH)–immunoreactive differentiated Lund human mesencephalic (LUHMES)primarily being toxic to dopamine neurons. In addition, MSDC–0160 counteracts both MPP+–induced shortening of neurite lengthand reduces branching in both LUHMES cells. MSDC–0160 (10 or 100 μM) prevents the loss of GFP–fluorescent dopaminergicneurons induced by MPP+ (0.75 mM) in nematodes (P =0.0001), whereas 1 μM MSDC–0160 does not. MSDC–0160 (10 μM) blocksLPS–induced increases in iNOS expression in BV2 cell lysates. MSDC–0160 is mainly to prevent the activation of mTOR produced bythe insulin/IGF–1 signaling pathway and restores IGF–1–induced akt phosphorylation. MSDC–0160 (10–20 μM) in conbination withIGF–1 prevents the loss of insulin content and maintains insulin secretion. Treatment of human islets with MSDC–0160 (1–50 μM)treatment with PPARγ ligands (MSDC 0160) and γ–radiation synergistically induces caspase–dependent apoptotic cell death, andPPARγ ligands significantly enhance the γ–radiation–induced DNA damage response in a PPARγ–independent manner[3].
activates AMPK and downregulates mTOR. MSDC–0160 (1–50 μM) treatment maintains human β–cell phenotype[2]. The combinedthe metabolic changes rather than to directly inhibit mTOR kinase activity[1]. PPARγ sparing TZD, MSDC–0160, reduces resistance in
In Vivo: MSDC–0160 (30 mg/kg per day, p.o.) can be observed in plasma and brain tissue of the mice, proving MSDC–0160 caneffectively enter the brain. MSDC–0160 (30 mg/kg per day, p.o.) treatment 3 days after MPTP injection, improves motor behavior,protects nigrostriatal neurons, and suppresses disease progression in the MPTP mouse model of Parkinson’s disease (PD), improvesmotor behavior in the open–field and rotarod tests in the En1+/– genetic mouse model of PD, and prevents dopaminergicneurodegeneration in the En1+/– genetic mouse model of PD. MSDC–0160 (30 mg/kg, p.o.) modulates mTOR signaling in C.genetic mouse model of PD[1].
Animal Administration[1]
elegans and the MPTP mouse model of PD. MSDC–0160 down–regulates mTOR signaling and restores autophagy in the En1+/–
PROTOCOL (Extracted from published papers and Only for reference)
MSDC–0160 is dissolved in 1% methylcellulose with 0.01% Tween 80.
Ten– to 12–week–old male C57BL/6J mice weighing 24 to 28 g are housed under standard conditions: constant temperature (22°C),humidity (relative, 30%), and a 12–hour light/dark cycle, with free access to food and water. Procedures are performed during daylighthours. Mice are administered MSDC–0160 (30 mg/kg) by oral gavage beginning 24 hours before MPTP treatment. Next, mice receivefive consecutive doses of MPTP via intraperitoneal injection at 25 mg/kg per day along with coadministration of MSDC–0160, followed
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by 6 days of MSDC–0160 treatment. MSDC–0160 is dissolved in 1% methylcellulose with 0.01% Tween 80. Control mice receive vehicletreatment (1% methylcellulose with 0.01% Tween 80). In the modest pathology stage, mice are administered MSDC–0160 (30 mg/kgper day) by oral gavage for 7 days starting 3 days after MPTP (25 mg/kg per day) treatment. Seven days after MPTP treatment, miceare euthanized, and tissues are processed for further evaluation. Mice are randomized to the experimental groups.
References:
[1]. Rohatgi N, et al. Novel insulin sensitizer modulates nutrient sensing pathways and maintains β–cell phenotype in human islets. PLoS One. 2013 May 1;8(5):e62012.
[2]. Ghosh A, et al. Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration inexperimental models of Parkinson's disease.Sci Transl Med. 2016 Dec 7;8(368):368ra174.
Caution: Product has not been fully validated for medical applications. For research use only.
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