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A-769662

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Catalog No.
A3963
AMPK激活剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 700.00
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10mg
¥ 650.00
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25mg
¥ 1,400.00
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50mg
¥ 2,600.00
现货

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Background

A-769662 is a potent activator of AMPK with EC50 value of 0.8 μM in vitro[1].

AMPK(AMP-activated protein kinase) is a serine/threonine protein kinase which is formed by three proteins: α,β and γ subunits. They play important roles in both the activity and stabilities of AMPK. AMPK functions as sensors of cellular energy by detecting and reacting to the change of AMP: ATP ratio. AMPK plays an important role in regulating intracellular energy metabolism. AMPK inhibits ATP-consuming pathways containing cholesterol synthesis, fatty acid synthesisand gluconeogenesis. AMPK stimulates fatty acid oxidation and glycolysis which are ATP-generating processes. AMPK inhibits gluconeogenesis by suppressing the expression of glucose-6-phosphatase and PEPCK wich are two key gluconeogenic enzymes.[1]

A-769662 belongs to the thienopyridone family. It activates the activity of purified AMPK from diffrent tissues with a dose-dependent manner. A-769662 activated the activity of AMPK extracted from human embryonic kidney cells (HEKs), rat muscle, or rat heart with EC50 values of 1.1 mM, 1.9 mM, or 2.2mM, respectively. A-769662 inhibited the synthesis of fatty acid with IC50 value of 3.2mM in primary rat hepatocytes.[1] A769662 also has inhibition effect on the 26S proteasome with an AMPK-independent mechanism. A769662 does not inhibit the proteolytic activities of the 20S core subunit which is a novel mechanism. A769662 can cause the arrest of cell cycle by inhibiting the 26S proteasome[2]. A-769662 activates AMPK in an allosterically manner. It also inhibits Thr-172 dephosphorylation of AMPK.[3]

In mice treated with dose of 30mg/kg, A-769662 decreased the expression of FAS, G6Pase, and PEPCK in liver of. It also lowered plasma glucose by 40% and reduced body weight gain.[1]

References:
[1].  Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R et al: Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 2006, 3(6):403-416.
[2].  Moreno D, Knecht E, Viollet B, Sanz P: A769662, a novel activator of AMP-activated protein kinase, inhibits non-proteolytic components of the 26S proteasome by an AMPK-independent mechanism. FEBS Lett 2008, 582(17):2650-2654.
[3].  Sanders MJ, Ali ZS, Hegarty BD, Heath R, Snowden MA, Carling D: Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem 2007, 282(45):32539-32548.

文献引用

1. Cannon, Danielle Kathryn. "ASSESSING MENOPAUSAL FEMALE SUSCEPTIBILITY TO HEART DISEASE: A FOCUS ON AMPK’S ABILITY TO MITIGATE CARDIAC REMODELING THROUGH ESTROGEN-DEPENDENT GENE PROGRAMS." The University of Arizona. 2019.
2. Wen Z, Jin K, et al. "N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation." Nat Immunol. 2019 Mar;20(3):313-325. PMID:30718913
3. Hubbard JA, Xiao B, et al. "Production and Crystallization of Full-Length Human AMP-Activated Protein Kinase (α1β1γ1)." Methods Mol Biol. 2018;1732:1-14. PMID:29480465
4. Oladimeji PO, Lin W, et al. "Glucose-dependent regulation of pregnane X receptor is modulated by AMP-activated protein kinase." Sci Rep. 2017 Apr 24;7:46751. PMID:28436464

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt360.39
Cas No.844499-71-4
FormulaC20H12N2O3S
SynonymsA-769662;A769662
Solubility≥18.0195 mg/mL in DMSO, <2.35 mg/mL in EtOH, <2.39 mg/mL in H2O
Chemical Name4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-6-oxo-7H-thieno[2,3-b]pyridine-5-carbonitrile
SDFDownload SDF
Canonical SMILESC1=CC=C(C(=C1)C2=CC=C(C=C2)C3=CSC4=C3C(=C(C(=O)N4)C#N)O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

原代大鼠肝细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

4 h

实验结果

A-769662以剂量依赖性方式增加ACC磷酸化,ACC被AMPK磷酸化。A-769662抑制脂肪酸合成,IC50值为3.2 μM。浓度高达100 μM的A-769662处理大鼠肝细胞未观察到细胞毒性。

动物实验[1]:

动物模型

Sprague Dawley (SD) 大鼠

剂量

30 mg/kg,口服灌胃

实验结果

在前3小时,A-769662显著降低呼吸交换率(RER),在随后的3小时内,RER有一个较小程度但显著的增加。A-769662将大鼠肝脏中丙二酰CoA水平降低33%。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Cool B, Zinker B, Chiou W, et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab, 2006, 3(6): 403-416.

生物活性

描述 A-769662是AMPK的小分子激活剂,IC50值为116 nM。
靶点 AMPK          
IC50 116 nM (EC50)          

质量控制

化学结构

A-769662

相关生物数据

A-769662

相关生物数据

A-769662

相关生物数据

A-769662

相关生物数据

A-769662