2. GPCR/G Protein
  3. Arrestin
  4. SKL1223

SKL1223 是一种口服有效的硫氧还蛋白相互作用蛋白 (TXNIP) 抑制剂，其 IC50 为 0.64 µM。SKL1223 可与 TXNIP 启动子的 E-box 区域相互作用，抑制 TXNIP 的转录及相关信号通路。SKL1223 可减少肝葡萄糖输出。SKL1223 通过调节胰高血糖素的作用发挥降糖效应，并可调节 Streptozotocin (STZ) (HY-13753) 诱导型及肥胖诱导型糖尿病小鼠的血糖水平。SKL1223 可用于 1 型糖尿病和 2 型糖尿病的研究。

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SKL1223

SKL1223 Chemical Structure

CAS No. : 3093938-66-7

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SKL1223 相关抗体

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

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].

体外研究
(In Vitro)

SKL1223 (10-20 μM; 24 h) 可显著下调大鼠 INS-1 细胞和 NES2Y 细胞中 TXNIP 的 mRNA 表达水平，且在大鼠 INS-1 细胞中通过 RNA 测序证实该下调作用具有剂量依赖性[1]。
SKL1223 (0.2-25 μM; 24 h) 可剂量依赖性降低大鼠 INS-1 细胞、NES2Y 细胞、αTC1-6 细胞及原代小鼠肝细胞中 TXNIP 蛋白的表达，且大鼠 INS-1 细胞中的蛋白水平降低已通过共聚焦显微镜得到证实[1]。
SKL1223 (5-20 μM; 24 h) 可剂量依赖性降低 αTC1-6 细胞的基础胰高血糖素分泌，且不改变细胞内胰高血糖素含量，对精氨酸+去甲肾上腺素或低葡萄糖条件下的刺激分泌无影响[1]。
SKL1223 (5-20 μM; 6-24 h) 可抑制野生型原代小鼠肝细胞中胰高血糖素诱导的糖异生基因表达、葡萄糖生成以及 cAMP 产生，其中葡萄糖生成和 cAMP 相关效应不依赖于 TXNIP，但依赖于胰高血糖素受体[1]。

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

SKL1223 相关抗体:

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.
体内研究
(In Vivo)

SKL1223 (口服；3 周) 可通过减少血清胰高血糖素分泌、降低甘油三酯水平并抑制肝脏糖异生酶的表达，改善正常雄性 C57BL/6J 小鼠的葡萄糖稳态，且不会改变体重或胰岛素水平[1]。
SKL1223 (口服) 可通过降低血清胰高血糖素水平、降低血糖和尿糖并保护胰岛 β 细胞功能，改善 STZ 诱导的 1 型糖尿病雄性 C57BL/6J 小鼠的葡萄糖稳态，且疗效优于标准口服抗糖尿病药物[1]。
SKL1223 (口服，4 周) 可通过降低血清胰高血糖素水平、降低血糖并改善肝脏脂肪变性，改善肥胖的瘦素受体缺陷型 2 型糖尿病 db/db 小鼠的葡萄糖稳态，且不改变体重或胰岛素水平[1]。
SKL1223 (70 mg/kg；口服；每日；14 天) 不会改变 TXNIP 敲除雄性 C57BL/6J 小鼠的葡萄糖稳态，但会导致空腹血清胰高血糖素水平轻微升高，证实其血糖调节作用依赖于 TXNIP[1]。

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.
分子量

317.34

Formula

C19H15N3O2
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

SKL1223 相关分类

  • 摩尔计算器

  • 稀释计算器

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SKL12233093938-66-7SKL 1223SKL-1223Arrestinrat INS-1 cellsE-box regionTXNIPtype 1 diabetesTXNIP promotertype 2 diabetesαTC1-6 cellsC57BL/6J miceprimary mouse hepatocytesNES2Y cellsInhibitorinhibitorinhibit

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