A-769662
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
A-769662是一种有效的AMPK激活剂，在体外的EC50值为0.8μM[1]。
AMP激活蛋白激酶（AMPK）是一种丝氨酸/苏氨酸蛋白激酶，由三种亚基形成：α、β和γ亚基，它们在AMPK的活性和稳定性方面具有重要作用。 AMPK作为细胞能量的传感器，检测和反应AMP: ATP比值的变化。AMPK在调控细胞内能量代谢方面具有重要作用。AMPK抑制ATP消耗通路，包括胆固醇合成、脂肪酸合成和糖异生。AMPK刺激产生ATP的脂肪酸氧化和糖酵解过程。AMPK通过抑制葡萄糖-6-磷酸酶和PEPCK的表达（两个关键的糖异生酶），从而抑制糖异生[1]。
A-769662属于thienopyridone家族，以剂量依赖的方式激活不同组织来源的纯化AMPK的活性。A-769662激活从人胚胎肾细胞（HEKs）、大鼠肌肉或大鼠心脏提取的AMPK活性，EC50值分别为1.1 mM、1.9 mM或2.2 mM。在原代大鼠肝细胞中，A-769662抑制脂肪酸的合成，IC50值为3.2 mM [1]。A769662也以AMPK不依赖的机制抑制26S蛋白酶体，从而引起细胞周期停滞，而不抑制20S核心亚基的蛋白水解活性[2]。A-769662以变构的方式激活AMPK，也抑制AMPK的Thr-172去磷酸化[3]。
在小鼠中，A-769662以30 mg/kg的剂量给药后减少肝脏中FAS、G6Pase和PEPCK的表达，也降低了40%的血浆葡萄糖水平，并减少体重的增加[1]。
参考文献：
[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.
- 1. Pier, Marissa. "AMP-Activated Protein Kinase (AMPK) and Estrogen-Dependent Mechanisms Underlying Increased Susceptibility to Cardiovascular Disease During Menopause." The University of Arizona.
- 2. Yong Heui Jeon, Minzhen He, et al. "Adiponectin enhances the bioenergetics of cardiac myocytes via an AMPK-and succinate dehydrogenase-dependent mechanism." Cell Signal. 2021 Feb;78:109866. PMID: 33271223
- 3. Tereza Moore, Rolando E. Yanes, et al. "AMP-independent activator of AMPK for treatment of mitochondrial disorders." PLoS One. 2020 Oct 14;15(10):e0240517. PMID: 33052980
- 4. Matzinger M, Fischhuber K, et al. "AMPK leads to phosphorylation of the transcription factor Nrf2, tuning transactivation of selected target genes." Redox Biol. 2019 Nov 27;29:101393. PMID: 31805502
- 5. 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.
- 6. 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
- 7. 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
- 8. 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 360.39 |
| Cas No. | 844499-71-4 |
| Formula | C20H12N2O3S |
| Synonyms | A-769662; A769662 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥18.02 mg/mL in DMSO |
| Chemical Name | 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-6-oxo-7H-thieno[2,3-b]pyridine-5-carbonitrile |
| SDF | Download SDF |
| Canonical SMILES | C1=CC=C(C(=C1)C2=CC=C(C=C2)C3=CSC4=C3C(=C(C(=O)N4)C#N)O)O |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验[1]: | |
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细胞系 |
原代大鼠肝细胞 |
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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 |
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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]: | |
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动物模型 |
Sprague Dawley (SD) 大鼠 |
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剂量 |
30 mg/kg，口服灌胃 |
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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。 |
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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. |
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| 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) | |||||
质量控制和MSDS
- 批次:
化学结构
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