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A-1803 A-769662, >99%
M.W. 360.39
C20H12N2O3S
[844499-71-4]
Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 33 mg/mL; soluble in ethanol at 5 mg/mL with slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A
•A-769662 is a potent, reversible activator of AMP-activated protein kinase (AMPK). AMPK is an αβγ heterotrimer and plays an important role in regulating cellular and whole-body metabolism. A-769662 only activates AMPK heterotrimers containing the β1 subunit. A-769662 activates AMPK through the β subunit carbohydrate-binding module and the γ subunit but not the AMP-binding sites. Scott, J.W., et al. "Thienopyridone drugs are selective activators of AMP-activated protein kinase β1-containing complexes." Chem. Biol. 15: 1220-1230 (2008).
•A-769662 stimulated partially purified rat liver AMPK with an EC50 of 0.8 µM and inhibited fatty acid synthesis in primary rat hepatocytes with an IC50 of 3.2 µM. A-769662 decreased liver malonyl CoA levels of Sprague Dawley rats and the respiratory exchange ratio, VCO2/VO2, and thus increased rate of whole-body fatty acid oxidation. A-769662 reduced hepatic expression of PEPCK, G6Pase, and FAS, decreased body weight gain, lowered plasma glucose by 40%, and reduced both plasma and liver triglyceride levels in ob/ob mice. Cool, B., et al. "Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome." Cell Metab. 3: 403-416 (2006).
•A-769662 induces allosteric activation of AMP-activated protein kinase (AMPK) and inhibition of dephosphorylation of AMPK on Thr-172, similar to the effects of AMP. Sanders, M.J., et al. "Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family." J. Biol. Chem. 282: 32539-32548 (2007).
•The effects of A-769662 are not dependent on the upstream kinase used in intact cells. Göransson, O., et al. "Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase." J. Biol. Chem. 282: 32549-32560 (2007).
•In skeletal muscle, A-769662 activates β1-containing AMPK complexes, but induces glucose uptake via a PI3 kinase-dependent pathway. Treebak, J.T., et al. "A-769662 activates AMPK β1-containing complexes but induces glucose uptake through a PI3 kinase-dependent pathway in mouse skeletal muscle." Am. J. Physiol. Cell Physiol. 297: C1041-C1052 (2009).
•A-769662 inhibits 3T3-L1 adipocyte differentiation and may be used to treat obesity. Zhou, Y., et al. "Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesis." Biol. Pharm. Bull. 32: 993-998 (2009).
•A-769662 inhibited the function of the 26S proteasome via an AMPK-independent mechanism. Moreno, D., et al. "A769662, a novel activator of AMP-activated protein kinase, inhibits non-proteolytic components of the 26S proteasome by an AMPK-independent mechanism." FEBS Lett. 582: 2650-2654 (2008).
•Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.
•This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, P |