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Compound class: Synthetic organic
Comment: A-769662 is a small molecule activator of AMP-activated protein kinase (AMPK). Its chemical structure was originally disclosed by Cool et al. (2006) , in which it was used to demonstrate that AMPK activation is a feasible approach for the treatment of the metabolic syndrome and type 2 diabetes. A-769662 activates AMPK both allosterically (as evidenced by its ability to activate a mutant AMPK γ subunit that is resistant to endogenous AMP-induced activation) and by inhibiting dephosphorylation of AMPK on Thr172 . A-769662 is suitable as as experimental tool to understand the physiological roles of AMPK in vitro and in vivo. Use of A-769662 has also confirmed AMPK's role as an autophagy target, whose activation is able to ameliorate neurodegeneration in animal models . AMPK activation induces autophagy in an mTOR-independent manner, so limits the risk of the potentially detrimental effects that mTOR inhibition may have on important cellular pathways in addition to autophagy.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
1. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R et al.. (2006)
Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome.
Cell Metab, 3 (6): 403-16. [PMID:16753576]
2. Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, Viollet B, Hardie DG, Sakamoto K. (2007)
Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase.
J Biol Chem, 282 (45): 32549-60. [PMID:17855357]
3. Sanders MJ, Ali ZS, Hegarty BD, Heath R, Snowden MA, Carling D. (2007)
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 (45): 32539-48. [PMID:17728241]
4. Walter C, Clemens LE, Müller AJ, Fallier-Becker P, Proikas-Cezanne T, Riess O, Metzger S, Nguyen HP. (2016)
Activation of AMPK-induced autophagy ameliorates Huntington disease pathology in vitro.
Neuropharmacology, 108: 24-38. [PMID:27133377]