A Potent and Selective AMPK Activator That Inhibits de Novo Lipogenesis.
ACS Med Chem Lett
; 1(9): 478-82, 2010 Dec 09.
Article
en En
| MEDLINE
| ID: mdl-24900234
ABSTRACT
AMP-activated protein kinase (AMPK) is a heterotrimeric kinase that regulates cellular energy metabolism by affecting energy-consuming pathways such as de novo lipid biosynthesis and glucose production as well as energy-producing pathways such as lipid oxidation and glucose uptake. Accordingly, compounds that activate AMPK represent potential drug candidates for the treatment of hyperlipidemia and type 2 diabetes. Screening of a proprietary library of AMP mimetics identified the phosphonic acid 2 that bears little structural resemblance to AMP but is capable of activating AMPK with high potency (EC50 = 6 nM vs AMP EC50 = 6 µM) and specificity. Phosphonate prodrugs of 2 inhibited de novo lipogenesis in cellular and animal models of hyperlipidemia.
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MEDLINE
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En
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ACS Med Chem Lett
Año:
2010
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Article