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A Potent and Selective AMPK Activator That Inhibits de Novo Lipogenesis.

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 ?M) and specificity. Phosphonate prodrugs of 2 inhibited de novo lipogenesis in cellular and animal models of hyperlipidemia.

SUBMITTER: Gomez-Galeno JE

PROVIDER: S-EPMC4007905 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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A Potent and Selective AMPK Activator That Inhibits de Novo Lipogenesis.

Gómez-Galeno Jorge E JE Dang Qun Q Nguyen Thanh H TH Boyer Serge H SH Grote Matthew P MP Sun Zhili Z Chen Mingwei M Craigo William A WA van Poelje Paul D PD MacKenna Deidre A DA Cable Edward E EE Rolzin Paul A PA Finn Patricia D PD Chi Bert B Linemeyer David L DL Hecker Scott J SJ Erion Mark D MD

ACS medicinal chemistry letters 20100830 9

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 ...[more]

PMID: 24900234

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