A-769662   Click here for help

GtoPdb Ligand ID: 10069

Synonyms: A769662
PDB Ligand
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) [1], 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 [3]. 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 [4]. 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.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 125.35
Molecular weight 360.06
XLogP 4.39
No. Lipinski's rules broken 0
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Canonical SMILES N#Cc1c(=O)[nH]c2c(c1O)c(cs2)c1ccc(cc1)c1ccccc1O
Isomeric SMILES N#Cc1c(=O)[nH]c2c(c1O)c(cs2)c1ccc(cc1)c1ccccc1O
InChI InChI=1S/C20H12N2O3S/c21-9-14-18(24)17-15(10-26-20(17)22-19(14)25)12-7-5-11(6-8-12)13-3-1-2-4-16(13)23/h1-8,10,23H,(H2,22,24,25)
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]