A-769662

Catalog No.S2697 Batch:S269704

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Technical Data

Formula

C20H12N2O3S
Molecular Weight 360.39 CAS No. 844499-71-4
Solubility (25°C)* In vitro DMSO 72 mg/mL (199.78 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM in cell-free assays, little effect on GPPase/FBPase activity.
Targets
AMPK [1]
(Cell-free assay)		 Fatty acid synthesis [1]
(in primary rat hepatocytes)
0.8 μM(EC50) 3.2 μM
In vitro 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 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]

Protocol (from reference)

Kinase Assay:

[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.
Cell Assay:

[3]
  • Cell lines

    MEF cells

  • Concentrations

    300 μM

  • Incubation Time

    24 hours

  • Method

    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.
Animal Study:

[1]
  • Animal Models

    Sprague Dawley rats

  • Dosages

    30 mg/kg

  • Administration

    Administered via i.p.

Customer Product Validation

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]

Data from [Data independently produced by Biochem Biophys Res Commun, 2013, 437(1), 1-6]

Selleck's A-769662 has been cited by 75 publications

Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas [ Nat Commun, 2023, 14(1):5913] PubMed: 37737247
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
AMPK regulates homeostasis of invasion and viability in trophoblasts by redirecting glucose metabolism: Implications for pre-eclampsia [ Cell Prolif, 2022, e13358.] PubMed: 36480593
Perfluorooctanoic acid alters the developmental trajectory of female germ cells and embryos in rodents and its potential mechanism [ Ecotoxicol Environ Saf, 2022, 236:113467] PubMed: 35390687
Akt/mTOR integrate energy metabolism with Wnt signal to influence wound epithelium growth inGekko Japonicus [ Communications Biology, 2022, 1018 (2022)] PubMed: None

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.