A-769662 化学構造
分子量: 360.39

品質と確認

カスタマーレビュー(4)

Quality Control & MSDS

製品情報

  • Compare AMPK Inhibitors
    AMPK阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 A-769662は0.8μMのEC50による強力な、可逆的なAMPを起動するプロテインキナーゼ(AMPK)活性剤で、3.2μMでIC50で脂肪酸合成を禁止します。
目標

AMPK

Fatty acid synthesis

IC50

0.8 μM

3.2 μM [1]

In vitro試験 A-769662 stimulates partially purified rat liver AMPK with EC50 with 0.8 μM. A-769662 activates AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC50s. EC50s determined for A-769662 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 A-769662 dose-dependently increases ACC phosphorylation, which correlated inhibition of fatty acid synthesis with IC50 of 3.2 μM. A-769662 also inhibits fatty acid sythesis in mouse hepatocytes with IC50 with 3.6 μM [1] A-769662 activates AMPK both allosterically and by inhibiting dephosphorylation of AMPK on Thr-172, similar to the effects of AMP. [2] A-769662 inhibits proteasomal function by an AMPK-independent mechanism. A-769662 affects the in vitro activity of purified 26S proteasomes but not the in vitro activity of purified 20S proteasomes. A-769662 has toxic effects on MEF cells. [3] A recent research shows A-769662 inhibited cell proliferation and DNA synthesis. [4]
In vivo試験 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. A-769662 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. [1]
臨床試験
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ:

[1]

96-well AMPK assay AMPK activity is measured by monitoring phosphorylation of the SAMS peptide substrate (20 mM in standard assays and 100 mM 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 A-769662 are preincubated with rat liver AMPK for 10 minutes at 20 times standard assay concentrations prior to dilution and measurement of AMPK activity.
Fatty Acid Synthesis Assay Primary rat hepatocytes are isolated and plated at 5 × 104 cells per well on BioCoat, collagen-coated, black-walled 96-well plates in DMEM supplemented with 10% FBS, 5 mM glucose, 1 mM sodium pyruvate, 2 mM L-glutamine, 25 mM HEPES, 0.1 m

細胞アッセイ:

[3]

細胞系 MEF cells
濃度 300 μM
処理時間 24 hours
方法

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:

[1]

動物モデル Sprague Dawley rats
製剤 A-769662 is dissolved in DMSO.
投薬量 30 mg/kg
管理 Administered via i.p.
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80 30 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download A-769662 SDF
分子量 360.39
化学式

C20H12N2O3S

CAS No. 844499-71-4
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 72 mg/mL (199.78 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 30 mg/mL
* <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.
化学名 Thieno[2,3-b]pyridine-5-carbonitrile, 6,7-dihydro-4-hydroxy-3-(2'-hydroxy[1,1'-biphenyl]-4-yl)-6-oxo-

研究分野

カスタマーレビュー (4)


Click to enlarge
Rating
Source Cancer Res, 2014, 74(1), 298-308. A-769662 purchased from Selleck
Method MTT
Cell Lines H1299, A549
Concentrations 100 nM
Incubation Time 48 h
Results A SIRT1 inhibitor (EX527) induced drug resistances under normoxia, which was reversed by an AMPK activator (A769662).

Click to enlarge
Rating
Source J Lipid Res, 2014, 55(7), 1254-1266. A-769662 purchased from Selleck
Method Immunoblotting
Cell Lines Ldlr-/- mice
Concentrations 30 mg/kg
Incubation Time 90 min
Results Mice were also injected with the potent synthetic AMPK activator A-76966, which increased AMPK and ACC phosphorylation ~ 2-fold.

Click to enlarge
Rating
Source Pharmacol Res, 2014, 81, 34-43. A-769662 purchased from Selleck
Method H<sub>2</sub>S-selective sensor
Cell Lines
Concentrations 0-250 uM
Incubation Time 10 min
Results Synthetic AMPK activator, A-769662, increased AMPK phosphorylation in a concentration-dependent manner. AMPK inhibitor, compound C, had no effect on AMPK phosphorylation in the absence of A-769662 but abolished enzyme stimulation induced by this activator.

Click to enlarge
Rating
Source Biochem Biophys Res Commun, 2013, 437(1), 1-6. A-769662 purchased from Selleck
Method Western blot
Cell Lines PANC-1 cells
Concentrations 10 uM
Incubation Time 2 h
Results Western blot results demonstrated that belinostat induced AMPK activation in a time-dependent manner. It showed that belinostat induced AMPK activation in a dose-dependent manner, and significant AMPK/ACC phosphorylation was observed by 1 or 10 uM of belinostat treatment. Two well-known AMPK activators AICAR and A-769662 also promoted AMPK activation in PANC-1 cells.

製品表彰状 (4)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の問い合わせをするならば、メッセージを残してください。

* 必須

Related AMPK 阻害剤

  • WZ4003

    WZ4003 is a highly specific NUAK kinase inhibitor with IC50 of 20 nM and 100 nM for NUAK1 and NUAK2, respectively, without significant inhibition on 139 other kinases.

  • VE-822

    VE-822 is a selective ATR inhibitor with Ki of < 0.2 nM, >170-fold ATR-selectivity over the closely related PI3K-related kinases ATM/DNA-PK.

  • AZ20

    AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM, 8-fold selectivity over mTOR.

  • AR-A014418

    AR-A014418 is an ATP-competitive, and selective GSK3β inhibitor with IC50 and Ki of 104 nM and 38 nM, without significant inhibition on 26 other kinases tested.

  • Acadesine

    ZMPの蓄積のアカデシン結果(それはAMPの両方の活性化効果を模倣します) AMPKとAMPKKの上で。

    Features:Acadesine is potentially first-in-class adenosine regulating agent (ARA)

  • Phenformin HCl

    Phenformin HCl is a hydrochloride salt of phenformin that is an anti-diabetic drug from the biguanide class.

  • Dorsomorphin 2HCl

    Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3.

  • MK-2206 2HCl

    MK-2206 2HClは高度選択的に Akt1, Akt2 and Akt3を抑制して、 IC50がそれぞれ 8 nM, 12 nM と 65 nMになる。

    Features:MK-2206是第一个进入临床研究阶段的Akt小分子变构抑制剂。

  • CHIR-99021 (CT99021) HCl

    CHIR-99021 (CT99021) HCl is hydrochloride of CHIR-99021, which is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; ability to distinguish between GSK-3 and its closest homologs Cdc2 and ERK2.

最近見られたアイテム

Tags: A-769662を買う | A-769662供給者 | A-769662を購入する | A-769662費用 | A-769662生産者 | オーダーA-769662 | A-769662代理店
お問い合わせ