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Art. -Nr.: HY-181335

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SKL1223

SKL1223 is an orally effective thioredoxin-interacting protein (TXNIP) inhibitor with an IC₅₀ of 0.64 µM. SKL1223 interacts with the E-box region of the TXNIP promoter to inhibit TXNIP transcription and related signaling pathways. SKL1223 reduces hepatic glucose output. SKL1223 exerts hypoglycemic effects by regulating the action of glucagon, and modulates blood glucose levels in Streptozotocin (HY-13753)-induced and obesity-induced diabetic mice. SKL1223 can be used in the research of type 1 diabetes and type 2 diabetes.

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CAS. Nr.: 3093938-66-7
Formel: C₁₉H₁₅N₃O₂
Molecular Weight:317.34

Speicherung:

Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month

SKL1223 Chemical Structure

CAS. Nr.: 3093938-66-7

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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In Vitro

SKL1223 (10-20 μM; 24 h) significantly downregulates TXNIP mRNA expression in rat INS-1 cells and NES2Y cells, with dose-dependent downregulation confirmed by RNA-sequencing in rat INS-1 cells^[1].
SKL1223 (0.2-25 μM; 24 h) dose-dependently reduces TXNIP protein expression in rat INS-1 cells, NES2Y cells, αTC1-6 cells, and primary mouse hepatocytes, with reduced protein levels confirmed by confocal microscopy in rat INS-1 cells^[1].
SKL1223 (5-20 μM; 24 h) dose-dependently reduces basal glucagon secretion in αTC1-6 cells without altering intracellular glucagon content, with no effect on stimulated secretion from arginine + norepinephrine or low glucose conditions^[1].
SKL1223 (5-20 μM; 6-24 h) suppresses glucagon-induced gluconeogenic gene expression, glucose output, and cAMP production in wild-type primary mouse hepatocytes, with the glucose output and cAMP effects independent of TXNIP but dependent on the glucagon receptor^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Real Time qPCR^[1]

Cell Line:

rat INS-1 cells, NES2Y cells
Concentration:

10 μM (qRT-PCR in INS-1 and NES2Y cells); 10-20 μM (RNA-sequencing in INS-1 cells)
Incubation Time:

24 h
Result:

Significantly reduced TXNIP mRNA expression in rat INS-1 cells and NES2Y cells.
Confirmed dose-dependent downregulation of the TXNIP gene in rat INS-1 cells via RNA-sequencing, with corresponding reduction in TXNIP protein generation.

Western Blot Analysis^[1]

Cell Line:

rat INS-1 cells, NES2Y cells, αTC1-6 mouse insulinoma alpha cells, primary mouse hepatocytes
Concentration:

0.2, 0.4, 0.8, 1.6, 3.2, 6.25, 12.5 and 25 μM
Incubation Time:

24 h
Result:

Caused a dose-dependent reduction in TXNIP protein expression in all tested cell types.
Showed a significant reduction in green fluorescent-labeled TXNIP protein in rat INS-1 cells via confocal microscopy.

In Vivo

SKL1223 (p.o.; 3 weeks) improves glucose homeostasis in normal male C57BL/6J mice by reducing serum glucagon secretion, lowering triglyceride levels, and suppressing hepatic gluconeogenic enzyme expression, without altering body weight or insulin levels^[1].
SKL1223 (p.o.) improves glucose homeostasis in STZ-induced type 1 diabetic male C57BL/6J mice by reducing serum glucagon levels, lowering blood and urine glucose, and preserving pancreatic beta-cell function, with greater efficacy than standard oral anti-diabetic drugs^[1].
SKL1223 (p.o.; 4 weeks) improves glucose homeostasis in obese, leptin receptor-deficient type 2 diabetic db/db mice by reducing serum glucagon levels, lowering blood glucose, and ameliorating hepatic steatosis, without altering body weight or insulin levels^[1].
SKL1223 (70 mg/kg; p.o.; daily; 14 days) does not alter glucose homeostasis in TXNIP knockout male C57BL/6J mice, but causes a marginal increase in fasting serum glucagon levels, confirming its glucose-regulating effects are TXNIP-dependent^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6J TXNIP-/- (8-week-old male; TXNIP deficiency)^[1]
Dosage:

70 mg/kg
Administration:

p.o.; daily; 14 days
Result:

Showed no significant change in body weight compared to untreated TXNIP-/- controls.
Exhibited no significant difference in non-fasting blood glucose levels, unaffected glucose tolerance, and unchanged fasting blood glucose levels.
Caused a marginal increase in fasting serum glucagon levels compared to controls.

Chemical Information

CAS. Nr. 3093938-66-7
Appearance Solid
Molecular Weight 317.34
Formel C₁₉H₁₅N₃O₂
Color White to off-white
SMILES

C1(NCC2=CC=CO2)=CC=C(C=C1)C3=NC(C4=CC=CC=C4)=NO3
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
In solvent	-80°C	6 months
	-20°C	1 month

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Wang X, et al. Orally Available Small Molecule Regulates TXNIP Expression and Glucagon Action for the Treatment of Diabetes.

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Bioz

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100 mg

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Biologische Aktivität
- Beschreibung
- In Vitro
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise

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SKL1223

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