Azemiglitazone (MSDC-0602)

Catalog No.S7454 Batch:S745401

Technical Data

Formula	C₁₉H₁₇NO₅S
Molecular Weight	371.41	CAS No.	1133819-87-0
Solubility (25°C)*	In vitro	DMSO	82 mg/mL (220.78 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Azemiglitazone (MSDC-0602) is a direct mitochondrial pyruvate carrier (MPC) inhibitor that modulates central carbon metabolism in mice and humans.

Targets

MPC ^[1]

In vitro

Azemiglitazone (MSDC-0602) is a modified hiazolidinediones (TZDP) with alterations in the carbon backbone that limit the ability to bind PPARγ, with the IC50 for PPARγ of 18.25 μM. Azemiglitazone (MSDC-0602) also shows the affinity for mitochondrial binding, with the IC50 of 1.38 μM. Using a Gal4-PPARγ construct containing the ligand binding domain of mouse PPARγ, MSDC-0602 only minimally activates Gal4-PPARγ in HepG2 cells even at a concentration of 50 μM.<a class="sref" href="#s_ref">[1]</a><a class="sref" href="#s_ref">[2]</a>

In vivo

Azemiglitazone (MSDC-0602) corrects plasma glucose, nonesterified fatty acids, triglycerides, cholesterol, and insulin concentrations, which are elevated in ob/ob mice compared with lean controls. Treatment with Azemiglitazone (MSDC-0602) also significantly improved glucose and insulin tolerance in ob/ob mice.<a class="sref" href="#s_ref">[2]</a>

Protocol (from reference)

Kinase Assay:^{^[2]}	PPAR Binding Assays TZD binding to the ligand binding domain of PPARγ was assessed in a LanthaScreen ^TMTR-FRET competitive binding assay performed according the protocol of the manufacturer (Invitrogen). IC 50 values for the PPARγ LanthaScreen were determined using Gen5 software (BioTek Instruments, Inc.). R² values for individual IC50 values ranged from 0.983 to 0.999 based on three separate assays for each compound.
Cell Assay:^{^[2]}	Cell lines HepG2 hepatoma cells Concentrations 0.5 nM, 5 nM, 50 nM, 0.5 μM, 5 μM and 50μM Incubation Time 48 h Method HepG2 hepatoma cells were co-transfected by calcium phosphate coprecipitation with expression vectors for Gal4-PPARγ (ligand binding domain only) or Gal4-PPARα, heterologous firefly luciferase reporter construct driven by five copies of a Gal4 response element, and SV40-driven renilla luciferase reporter construct. Transfected cells were treated with PPARγ agonists (rosiglitazone and pioglitazone), PPARα agonist (GW7647), or MSDC-0602 for 24 h. Cell lysate firefly and renilla luciferase activity was assessed 48 h later by using the Dual-Glo kit. Firefly luciferase activity was corrected for renilla luciferase activity, and DMSO (vehicle) values were normalized to 1.0.

Kinase Assay:^{^[2]}

PPAR Binding Assays
TZD binding to the ligand binding domain of PPARγ was assessed in a LanthaScreen ^TMTR-FRET competitive binding assay performed according the protocol of the manufacturer (Invitrogen). IC 50 values for the PPARγ LanthaScreen were determined using Gen5 software (BioTek Instruments, Inc.). R² values for individual IC50 values ranged from 0.983 to 0.999 based on three separate assays for each compound.

Cell Assay:^{^[2]}

Cell lines
HepG2 hepatoma cells
Concentrations
0.5 nM, 5 nM, 50 nM, 0.5 μM, 5 μM and 50μM
Incubation Time
48 h
Method
HepG2 hepatoma cells were co-transfected by calcium phosphate coprecipitation with expression vectors for Gal4-PPARγ (ligand binding domain only) or Gal4-PPARα, heterologous firefly luciferase reporter construct driven by five copies of a Gal4 response element, and SV40-driven renilla luciferase reporter construct. Transfected cells were treated with PPARγ agonists (rosiglitazone and pioglitazone), PPARα agonist (GW7647), or MSDC-0602 for 24 h. Cell lysate firefly and renilla luciferase activity was assessed 48 h later by using the Dual-Glo kit. Firefly luciferase activity was corrected for renilla luciferase activity, and DMSO (vehicle) values were normalized to 1.0.

References

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