A-769662 (Synonyms: A-769662;A769662) |
| Catalog No.GC11234 |
A-769662 is an activator of AMP-activated protein kinase, which has an EC50 value of 0.8μM.
Products are for research use only. Not for human use. We do not sell to patients.
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.
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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 | |
| Synonyms | A-769662;A769662 | ||
| Chemical Name | 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 | ||
| Formula | C20H12N2O3S | M.Wt | 360.39 |
| Solubility | ≥ 18.0195 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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