AS1842856
(Synonyms: 5-氨基-7-(环己基氨基)-1-乙基-6-氟-1,4-二氢-4-氧代-3-喹啉羧酸) 目录号 : GC19040
AS1842856 is a cell permeable inhibitor that inhibits Foxo1 transcriptional activity with IC50=33 nM.
Cas No.:836620-48-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
3T3L1 preadipocytes |
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Preparation Method |
Cell were cultured(with or without AS1842856) in basal medium (0-2 days), adipocyte differentiation was induced with differentiation medium I(3-4 days) and differentiation medium (5-6 days), and then the cells were maintained in basal medium (7-12 days). |
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Reaction Conditions |
1.0 µM AS1842856; 0-12 days |
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Applications |
AS1842856 continued to inhibit Foxo1, preventing adipocyte differentiation. |
| Animal experiment [2]: | |
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Animal models |
Foxc2 +/- mice(lymphedema-distichiasis mouse model ) |
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Preparation Method |
Mice were injected with AS1842856 for 2 weeks. |
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Dosage form |
10 mg/kg AS1842856;i.p.;(P) 7-21(2 weeks) |
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Applications |
AS1842856 treatment increases the valve number in Foxc2 heterozygous mice. |
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References: [1]. Zou P, Liu L, et,al. Targeting Foxo1 with AS1842856 suppresses adipogenesis. Cell Cycle. 2014;13(23):3759-67. doi: 10.4161/15384101.2014.965977. PMID: 25483084; PMCID: PMC4613185. | |
AS1842856 is a cell permeable inhibitor that inhibits Foxo1 transcriptional activity with IC50=33 nM.AS1842856 can directly bind activated Foxo1, but does not bind Foxo1 phosphorylated at Ser256. AS1842856 reduces Foxo1 activity only by binding to Foxo1, without affecting its transcription and protein expression. AS1842856 can inhibit autophagy[1-3].
AS1842856(1.0 µM; 0-12 days) continued to inhibit Foxo1, preventing adipocyte differentiation[4]. Treatment of BBC and GBM cancer cells with AS1842856(0.2-1.0 µM)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[5].
AS1842856-mediated(10 days ;5 mg/kg) chemical inhibition of Foxo1 reduced the expression of the atrophy-related ubiquitin ligases and significantly reversed the adverse cardiac remodeling while improving the contractile functions in the TLR2-KO mice[6].AS1842856(10 mg/kg;i.p.;(P) 7-21(2 weeks)) treatment increases the valve number in Foxc2 heterozygous mice[7].
AS1842856是一种细胞渗透性抑制剂,抑制Foxo1转录活性,IC50=33 nM。它可以直接结合活化的Foxo1,但不结合Ser256磷酸化的Foxo1。AS1842856仅通过与Foxo1结合而降低FoxO1活性,而不影响其转录和蛋白表达。AS1842856可以抑制自噬[1-3]。
AS1842856(1.0µM;0 ~ 12days)持续抑制Foxo1,阻止脂肪细胞分化[4]。AS1842856(0.2 ~ 1.0 µM)处理BBC和GBM癌细胞后,FAS (FAS细胞表面死亡受体)和BIM (BCL2L11)基因表达增加,凋亡标志物如膜联蛋白V和碘化丙啶阳性增加[5]。
AS1842856介导(10days;5 mg/kg)的Foxo1化学抑制降低了TLR2-KO小鼠萎缩相关泛素连接酶的表达,改善心脏收缩功能,逆转心脏重构[6]。AS1842856(10 mg/kg;i.p;(P) 7 - 21)处理可增加Foxc2杂合小鼠的瓣膜数[7]。
References:
[1]. Nagashima T, Shigematsu N, et,al. Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: improvement of fasting glycemia in diabetic db/db mice. Mol Pharmacol. 2010 Nov;78(5):961-70. doi: 10.1124/mol.110.065714. Epub 2010 Aug 24. PMID: 20736318.
[2]. He J, Zhang A, et,al. The resistant effect of SIRT1 in oxidative stress-induced senescence of rat nucleus pulposus cell is regulated by Akt- Foxo1 pathway. Biosci Rep. 2019 May 10;39(5):BSR20190112. doi: 10.1042/BSR20190112. PMID: 30967498; PMCID: PMC6509061.
[3]. Tanaka H, Nagashima T, 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. doi: 10.1016/j.ejphar.2010.07.018. Epub 2010 Jul 23. PMID: 20655898.
[4]. Zou P, Liu L, et,al. Targeting Foxo1 with AS1842856 suppresses adipogenesis. Cell Cycle. 2014;13(23):3759-67. doi: 10.4161/15384101.2014.965977. PMID: 25483084; PMCID: PMC4613185.
[5]. Flores D, Lopez A, et,al. The Foxo1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells. FEBS Open Bio. 2023 Feb;13(2):352-362. doi: 10.1002/2211-5463.13547. Epub 2023 Jan 16. PMID: 36602390; PMCID: PMC9900086.
[6]. Spurthi KM, Sarikhani M, et,al.Toll-like receptor 2 deficiency hyperactivates the Foxo1 transcription factor and induces aging-associated cardiac dysfunction in mice. J Biol Chem. 2018 Aug 24;293(34):13073-13089. doi: 10.1074/jbc.RA118.001880. Epub 2018 Jun 21. PMID: 29929978; PMCID: PMC6109936.
[7]. Ogunsina O, Banerjee R, et,al.Pharmacological inhibition of Foxo1 promotes lymphatic valve growth in a congenital lymphedema mouse model. Front Cell Dev Biol. 2023 Jan 5;10:1024628. doi: 10.3389/fcell.2022.1024628. PMID: 36742198; PMCID: PMC9890395.
| Cas No. | 836620-48-5 | SDF | |
| 别名 | 5-氨基-7-(环己基氨基)-1-乙基-6-氟-1,4-二氢-4-氧代-3-喹啉羧酸 | ||
| Canonical SMILES | O=C(C1=CN(CC)C2=C(C(N)=C(F)C(NC3CCCCC3)=C2)C1=O)O | ||
| 分子式 | C18H22FN3O3 | 分子量 | 347.38 |
| 溶解度 | DMSO : 7.6 mg/mL (21.88 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8787 mL | 14.3935 mL | 28.7869 mL |
| 5 mM | 0.5757 mL | 2.8787 mL | 5.7574 mL |
| 10 mM | 0.2879 mL | 1.4393 mL | 2.8787 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。