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AS1708727 Sale

目录号 : GC62309

AS1708727 是口服有效的 Foxo1 抑制剂,其对 G6Pase 和 PEPCK 的 EC50 值分别为 0.33 μM 和0.59 μM。

AS1708727 Chemical Structure

Cas No.:1253226-93-5

规格 价格 库存 购买数量
5 mg
¥2,700.00
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10 mg
¥4,320.00
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25 mg
¥8,550.00
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50 mg
¥13,050.00
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100 mg
¥20,250.00
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Sample solution is provided at 25 µL, 10mM.

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产品描述

AS1708727 is an orally active Foxo1 inhibitor, with EC50 values of 0.33 μM and 0.59 μM for G6Pase and PEPCK, respectively[1].

AS1708727 suppresses increases in blood glucose level by inhibiting gluconeogenic gene expression[1].

AS1708727 (30 to 300 mg/kg, orally) reduces both blood glucose and triglyceride levels, exhibiting anti-diabetic effects[1].

[1]. Hirotsugu Tanaka, et al. Effects of the Novel Foxo1 Inhibitor AS1708727 on Plasma Glucose and Triglyceride Levels in Diabetic Db/Db Mice. Eur J Pharmacol. 2010 Oct 25;645(1-3):185-91.

Chemical Properties

Cas No. 1253226-93-5 SDF
分子式 C24H24Cl2N2O2 分子量 443.37
溶解度 DMSO : 41.67 mg/mL (93.98 mM; Need ultrasonic) 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 2.2555 mL 11.2773 mL 22.5545 mL
5 mM 0.4511 mL 2.2555 mL 4.5109 mL
10 mM 0.2255 mL 1.1277 mL 2.2555 mL
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Research Update

Effects of the novel Foxo1 inhibitor AS1708727 on plasma glucose and triglyceride levels in diabetic db/db mice

Eur J Pharmacol 2010 Oct 25;645(1-3):185-91.PMID:20655898DOI:10.1016/j.ejphar.2010.07.018.

Recent evidence suggests that the forkhead transcription factor Foxo1 plays an important role in the regulation of glucose and triglyceride metabolism at the gene transcription level for glucose-6 phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), and apolipoprotein C-III (apoC-III). Here, we report on the pharmacological effects of the novel Foxo1 inhibitor AS1708727, which we identified by compound screening. Chronic treatment of diabetic db/db mice with AS1708727 for four days significantly reduced blood glucose and triglyceride levels with decrease of gene expression levels of hepatic G6Pase, PEPCK, and apoC-III. No reports have yet examined the influence of Foxo1 inhibitors on these pharmacological effects. In this study, we newly identified a Foxo1 inhibitor compound capable of exerting both an anti-hypertriglyceridemic and anti-hyperglycemic effect. These effects were dependent on maintaining a stable blood concentration of AS1708727 and achieving a high rate of compound transition to the liver. We also investigated the action mechanism of AS1708727 on gluconeogenesis in vitro and in vivo. The compound inhibited gene expression of key gluconeogenic molecules and suppressed gluconeogenesis in Fao hepatocyte cells in vitro. Further, in the pyruvate challenge study using db/db mice in vivo, AS1708727 suppressed increases in blood glucose level by inhibiting gluconeogenic gene expression. These results indicate that the novel Foxo1 inhibitor AS1708727 may exert anti-diabetic and anti-hypertriglyceridemic effects by improving blood glucose and triglyceride metabolism at the gene expression level, and may represent a new class of drugs useful for treating type 2 diabetes mellitus and hypertriglyceridemia.

The FOXO1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells

FEBS Open Bio 2023 Feb;13(2):352-362.PMID:36602390DOI:10.1002/2211-5463.13547.

Basal-like breast cancer (BBC) and glioblastoma multiforme (GBM) are poor-prognosis cancers that lack effective targeted therapies and harbor embryonic stem gene expression signatures. Recently, our group and others found that forkhead box transcription factor FOXO1 promotes stem gene expression in BBC and GBM cell lines. Given the critical role of cancer stem cells in promoting cancer progression, we examined the impact of FOXO1 inhibition with AS1842856 (a cell-permeable small molecule that directly binds to unphosphorylated FOXO1 protein to block transcriptional regulation) on BBC and GBM cell viability. We treated a set of BBC and GBM cancer cell lines with increasing concentrations of AS1842856 and found reduced colony formation. Treatment of BBC and GBM cancer cells with AS1842856 led to increases in FAS (FAS cell surface death receptor) and BIM (BCL2L11) gene expression, as well as increased positivity for markers for apoptosis such as annexin V and propidium iodide. Treatment with another FOXO1 inhibitor AS1708727 or FOXO1 RNAi also led to FAS induction. This work is the first to show that targeting BBC and GBM with FOXO1 inhibition leads to apoptosis. These novel findings may ultimately expand the repertoire of therapies for poor-prognosis cancers.