| Autor: |
William Craigo, Thanh H Nguyen, Matthew P. Grote, Qun Dang, Mingwei Chen, Deidre A. MacKenna, Edward Earl Cable, Scott J. Hecker, Zhili Sun, Paul A. Rolzin, Mark D. Erion, Serge H. Boyer, Jorge Gomez-Galeno, Paul D. van Poelje, Patricia D. Finn, David L. Linemeyer, Bert Chi |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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