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^[1].

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.

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.

317.34

C₁₉H₁₅N₃O₂

3093938-66-7

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

Room temperature in continental US; may vary elsewhere.

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