A-769662

製品コードS2697 バッチS269706

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H12N2O3S
分子量 360.39 CAS No. 844499-71-4
Solubility (25°C)* 体外 DMSO 72 mg/mL (199.78 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (13.87mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 A-769662は、強力で可逆的なAMPK活性化剤であり、細胞フリーアッセイでのEC50は0.8 µMで、GPPase/FBPase活性にはほとんど影響を与えません。
in vitro

A-769662 stimulates partially purified rat liver AMPK with EC50 with 0.8 μM. This compound activates AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC50s. EC50s determined for this chemical using partially purified AMPK extracts from rat heart, rat muscle, or human embryonic kidney cells (HEKs) are 2.2 mM, 1.9 mM, or 1.1 mM, respectively. A 4 hours treatment of primary rat hepatocytes with this compound dose-dependently increases ACC phosphorylation, which correlated inhibition of fatty acid synthesis with IC50 of 3.2 μM. It also inhibits fatty acid sythesis in mouse hepatocytes with IC50 with 3.6 μM This compound activates AMPK both allosterically and by inhibiting dephosphorylation of AMPK on Thr-172, similar to the effects of AMP. It inhibits proteasomal function by an AMPK-independent mechanism. This chemical affects the in vitro activity of purified 26S proteasomes but not the in vitro activity of purified 20S proteasomes. It has toxic effects on MEF cells. A recent research shows this compound inhibited cell proliferation and DNA synthesis.

in vivo

Short-term treatment of normal Sprague Dawley rats with A-769662 decreases liver malonyl CoA levels and the respiratory exchange ratio, VCO2/VO2, indicating an increased rate of whole-body fatty acid oxidation. Treatment of ob/ob mice with 30 mg/kg b.i.d. of this compound decreases hepatic expression of PEPCK, G6Pase, and FAS, lowers plasma glucose by 40%, reduced body weight gain and significantly decreases both plasma and liver triglyceride levels.

プロトコル(参考用のみ)

キナーゼアッセイ 96-well AMPK assay
AMPK activity is measured by monitoring phosphorylation of the SAMS peptide substrate (20 μM in standard assays and 100 μM in additivity assays) following a previously described protocol (Anderson et al., 2004). To determine whether A-769662-induced AMPK activation occurs in a reversible manner, AMP or this compound are preincubated with rat liver AMPK for 10 minutes at 20 times standard assay concentrations prior to dilution and measurement of AMPK activity.
細胞アッセイ 細胞株 MEF cells
濃度 300 μM
反応時間 24 hours
実験の流れ

Cell viability of MEF cells treated or not with A-769662 is performed as follows: cells are harvested by trypsinization and incubated with 0.5 mg/mL RNase and 50 μg/mL propidium iodine at room temperature in the dark; cell viability is analyzed by flow cytometry using a FACScanto flow cytometer, using an excitation laser at 488 nm and a propidium iodine fluorescence detection at 600 nm. To determine the proportion of cells in each phase of the cell cycle, cells are harvested by trypsinization, collected by centrifugation, washed in PBS and fixed overnight in 80% ethanol at -20 °C. Subsequently, these fixed cells are centrifuged to remove the fixative and incubated for 20 minutes in the dark at room temperature in PBS containing 0.5 mg/mL RNase and 50 μg/mL propidium iodine. Flow cytometry analysis is performed as above. The proportion of cells in G1, S, and G2 is determined using the MODFIT program. Cell culture pictures are taken at the indicated times using a camera coupled to an inverted microscope with a 20 × objective.
動物実験 動物モデル Sprague Dawley rats
投薬量 30 mg/kg
投与方法 Administered via i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/16753576/
  • https://pubmed.ncbi.nlm.nih.gov/17728241/
  • https://pubmed.ncbi.nlm.nih.gov/18593584/
  • https://pubmed.ncbi.nlm.nih.gov/22700432/

カスタマーフィードバック

Data from [Cancer Res, 2014, 74(1), 298-308]

Data from [Data independently produced by Pharmacol Res, 2014, 81, 34-43]

Data from [Data independently produced by J Lipid Res, 2014, 55(7), 1254-1266]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Propionibacterium acnes evades microbicidal phagocytosis by inhibiting the mitochondrial biogenesis of nucleus pulposus cells [ FEBS J, 2025, 10.1111/febs.70247] PubMed: 40891515
AMPK-YAP signaling pathway-mediated mitochondrial dynamics and mitophagy participate in the protective effect of silibinin on HaCaT cells under high glucose conditions [ Arch Biochem Biophys, 2025, 769:110433] PubMed: 40268264
Nuclear PD-L1 compartmentalization suppresses tumorigenesis and overcomes immunocheckpoint therapy resistance in mice via histone macroH2A1 [ J Clin Invest, 2024, 134(22)e181314] PubMed: 39545415
Maternal adiponectin restores cholinergic vasodilation in resistance vessels from adult offspring exposed to maternal obesity in utero [ bioRxiv, 2024, 2024.09.21.612123] PubMed: 39345365
Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas [ Nat Commun, 2023, 14(1):5913] PubMed: 37737247
Pathogenesis-related protein 1 suppresses oomycete pathogen by targeting against AMPK kinase complex [ J Adv Res, 2023, 43:13-26] PubMed: 36585103
A subset of VEGFR-TKIs activates AMPK in LKB1-mutant lung cancer [ Cancer Sci, 2023, 114(4):1651-1662] PubMed: 36459496
Loss of Lactate/Proton Monocarboxylate Transporter 4 Induces Ferroptosis via the AMPK/ACC Pathway and Inhibition of Autophagy on Human Bladder Cancer 5637 Cell Line [ J Oncol, 2023, 2023:2830306] PubMed: 36718218
Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis [ Mar Life Sci Technol, 2023, 5(2):196-210] PubMed: 37275542
Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress [ Nat Commun, 2022, 13(1):7031] PubMed: 36396642

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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