A-769662 (Synonyms: A-769662;A769662) |
| Catalog No.GC11234 |
A-769662 est un activateur de la kinase de protéine [1], ce qui a une valeur EC50 de 0,8µM.
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Cas No.: 844499-71-4
Sample solution is provided at 25 µL, 10mM.
A-769662 est un activateur de la kinase de protéine [1], ce qui a une valeur EC50 de 0,8µM[2]. A-769662 a activé l'activité de AMPK qui est prélevée des cellules rénales humaines (HEKs), de muscle de rat, ou de coeur de rat, les valeurs de EC50 sont respectivement 1,1mM, 1,9mM, ou 2,2mM[3].
A-769662 ( 100μM , 36h ) active la signalisation AMPK et la phosphorylation de complexe de tuberose 2 (TSC2)[4]. A-769662 ( 100μM , 24h ) a augmenté la phosphortlation AMPK dans les cellules rénales de rat que le glucose est normal( 5mM )[5].
Le traitement A -769662 (400/rat; 14 jours; L'injection intra - péritonéale) a réprimé la croissance des tumeurs de côlon de rat (modèèles de tumeurs CT26 de rats) et a entraîné les survies de long - terme[6]. A-769662(20pmol, 3jours, l'injection intravitréale) protège les rats contre la rétinopathie Methylglyoxal (MGO)-induite[7].
L’activation AMPK qui est promue par A -769662 peut induire l’autophagie par faciliter la formation des autophagosomes[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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Expériences cellulaires[1]: |
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Lignées cellulaires
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La lignée cellulaire neuro2a (N2A). |
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Méthode de préparation |
La lignée cellulaire N2A du Centre National de Science Cellulaire a été cultivée dans le substrat minimum essantiel (MEM)(contenant 5mM glucose) supplémenté de 10% sérum foetal bovin(FBS), glutamine(2mM), streptomycine/pénicilline(1%), à 37°C, dans une atmosphère humidifiée composée de 95% d’air et 5% de CO2. La condition de haut glucose a été créée par ajouter 25mM glucose dans le substrat. Les cellules ont été traitées par 25μM ou 50μM A769662 dans les 24h. |
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Conditions de réaction |
25μM ou 50μM A769662 dans les 24h.
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Domaines d'application |
Le traitement de A769662 améliore la inflammation neutre dans les cellules haut glucose - exposées. |
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Expériences animales[2]: |
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Modèles animaux |
Rats fémmininsBALB/cJ |
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Méthode de préparation |
Les tumeurs ont été établies par l’injection sous - cutanée de 1×105 cellules tumorales dans 100mL HBSS à la région flanquée droite des rats féminins BALB/cJ. Sept jours après l’injection des cellules tumorales, les animaux ont été combinés et ont été divisés au hasard en groupes expérimentaux désignés des tailles tumorales moyennnes comparables. Les traitements A769662 ont été effectués par l’injection intra - péritonéale (400mg par rat dans 200mL 5% DMSO + 10% polyéthylène glycol + 1% Tween 80 dans le tampon PBS) tous les jours pendant deux semaines. |
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Forme de dosage |
400mg/rat; 2 semaines; l’injection intra - péritonéale.
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Domaines d'application |
Le traitement A769662 a réprimé la croissance des tumeurs et a entraîné les survies de long - terme. |
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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 | |
| Synonymes | 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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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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