A-769662
(Synonyms: 4-羟基-3-(2'-羟基-1,1'-联苯-4-基)-6-氧代-6,7-二氢噻吩并[2,3-B]吡啶-5-甲腈,A-769662;A769662) 目录号 : GC11234
A-769662是AMP活化蛋白激酶的激活剂，EC50值为0.8μM。
Cas No.:844499-71-4
Sample solution is provided at 25 µL, 10mM.
A-769662 is an activator of AMP-activated protein kinase[1], which has an EC50 value of 0.8μM[2]. A-769662 activated the activity of AMPK extracted from human embryonic kidney cells (HEKs) , rat muscle, or rat heart with EC50 values of 1.1mM , 1.9mM , or 2.2mM, respectively[3].
A-769662 ( 100μM , 36h ) activates AMPK signaling and tumor suppressor tuberous sclerosis complex 2 ( TSC2 ) phosphorylation[4]. A-769662 ( 100μM , 24h ) increased AMPK phosphorylation in normal rat kidney cells under normal glucose ( 5mM )[5].
A-769662 (400mg/mouse; 14 days; intraperitoneal injection) treatment reduced mouse colon tumor (CT26 mice tumor models) growth and resulted in long-term survivors[6]. A-769662 (20pmol, 3 days, intravitreal injection) protect mice from Methylglyoxal (MGO)-induced retinopathy[7].
A-769662 promoting AMPK activation can induce the autophagy through facilitation of autophagosome formation[8] .
References:
[1] GORANSSON O, MCBRIDE A, HAWLEY S A, et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase [J]. J Biol Chem, 2007, 282(45): 32549-60.
[2] 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 [J]. Cell Metab, 2006, 3(6): 403-16.
[3] MORENO D, KNECHT E, VIOLLET B, et al. A769662, a novel activator of AMP-activated protein kinase, inhibits non-proteolytic components of the 26S proteasome by an AMPK-independent mechanism [J]. FEBS Lett, 2008, 582(17): 2650-4.
[4] KAKADIA J H, KHALID M U, HEINEMANN I U, et al. AMPK-mTORC1 pathway mediates hepatic IGFBP-1 phosphorylation in glucose deprivation: a potential molecular mechanism of hypoglycemia-induced impaired fetal growth [J]. J Mol Endocrinol, 2024, 72(3):
[5] SHRIKANTH C B, JAGANNATH S, CHILKUNDA N D. AMPK differentially alters sulphated glycosaminoglycans under normal and high glucose milieu in proximal tubular cells [J]. J Biochem, 2021, 169(1): 75-86.
[6] DAI X, BU X, GAO Y, et al. Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade [J]. Mol Cell, 2021, 81(11): 2317-31 e6.
[7] SEKAR P, HSIAO G, HSU S H, et al. Metformin inhibits methylglyoxal-induced retinal pigment epithelial cell death and retinopathy via AMPK-dependent mechanisms: Reversing mitochondrial dysfunction and upregulating glyoxalase 1 [J]. Redox Biol, 2023, 64(102786.
[8] YERRA V G, ARETI A, KUMAR A. Adenosine Monophosphate-Activated Protein Kinase Abates Hyperglycaemia-Induced Neuronal Injury in Experimental Models of Diabetic Neuropathy: Effects on Mitochondrial Biogenesis, Autophagy and Neuroinflammation [J]. Mol Neurobiol, 2017, 54(3): 2301-12.
A-769662是AMP活化蛋白激酶的激活剂[1]，EC50值为0.8μM[2]。A-769662可激活人胚胎肾细胞（HEKs）、大鼠肌肉细胞和大鼠心脏细胞中提取的AMPK的活性，EC50值分别为1.1mM、1.9mM和2.2mM[3]。
A-769662（100μM，36h）能激活AMPK信号和促进肿瘤抑制因子结节硬化复合体2（TSC2）的磷酸化[4]。A-769662（100μM，24h）在标准葡萄糖浓度（5mM）下可提高健康大鼠肾细胞内的AMPK磷酸化水平[5]。
A-769662 (400mg/只；14天；腹腔注射治疗可抑制小鼠结肠癌（CT26小鼠肿瘤模型）的生长并延长小鼠存活[6]。A-769662（20pmol，3天，玻璃体内注射）保护小鼠免受甲基乙二醛（MGO）诱导的视网膜病变[7]。
A-769662上调AMPK激活可通过自噬体形成诱导自噬[8]。
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Cell experiment[1]: |
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Cell lines |
The neuro2a (N2A) cell line. |
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Preparation method |
The N2A cell line from National Centre for Cell Sciences were grown in minimum essential medium (MEM) (containing 5mM glucose) supplemented with 10 % fetal bovine serum (FBS) , glutamine (2mM) , streptomycin/ penicillin (1%) , at 37℃, in a humidified atmosphere of 95% air and 5% CO2. High glucose condition was created by adding 25mM glucose to medium.The cells were treated with 25μM or 50μM A769662 within 24h. |
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Reaction Conditions |
25μM or 50μM within 24h. |
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Applications |
A769662 treatment ameliorates neuroinflammation in high glucose-exposed N2A cells. |
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Animal experiment[2]: |
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Animal models |
BALB/cJ female mice |
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Preparation method |
Tumors were established by subcutaneously injecting 1×105 tumor cells in 100mL HBSS into the right flank of BALB/cJ female mice .Seven days after tumor cells were injected, animals were pooled and randomly divided into designated experimental groups with comparable average tumor size. A769662 treatments were conducted by intraperitoneal injection (400mg per mouse in 200mL 5% DMSO + 10% polyethylene glycol + 1% Tween 80 in PBS buffer) every day for two weeks. |
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Dosage form |
400mg/mouse ; 2 weeks ; intraperitoneal injection. |
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Applications |
A769662 treatment reduced tumor growth and resulted in long-term survivors. |
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References: [1] YERRA V G, ARETI A, KUMAR A. Adenosine Monophosphate-Activated Protein Kinase Abates Hyperglycaemia-Induced Neuronal Injury in Experimental Models of Diabetic Neuropathy: Effects on Mitochondrial Biogenesis, Autophagy and Neuroinflammation [J]. Mol Neurobiol, 2017, 54(3): 2301-12. [2] DAI X, BU X, GAO Y, et al. Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade [J]. Mol Cell, 2021, 81(11): 2317-31 e6. |
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| Cas No. | 844499-71-4 | SDF | |
| 别名 | 4-羟基-3-(2'-羟基-1,1'-联苯-4-基)-6-氧代-6,7-二氢噻吩并[2,3-B]吡啶-5-甲腈,A-769662;A769662 | ||
| 化学名 | 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-6-oxo-7H-thieno[2,3-b]pyridine-5-carbonitrile | ||
| Canonical SMILES | C1=CC=C(C(=C1)C2=CC=C(C=C2)C3=CSC4=C3C(=C(C(=O)N4)C#N)O)O | ||
| 分子式 | C20H12N2O3S | 分子量 | 360.39 |
| 溶解度 | ≥ 18.0195 mg/mL in DMSO | 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 | 2.7748 mL | 13.8739 mL | 27.7477 mL |
| 5 mM | 0.555 mL | 2.7748 mL | 5.5495 mL |
| 10 mM | 0.2775 mL | 1.3874 mL | 2.7748 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet