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Literature DB >> 24900234

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

Jorge E Gómez-Galeno¹, Qun Dang¹, Thanh H Nguyen¹, Serge H Boyer¹, Matthew P Grote¹, Zhili Sun¹, Mingwei Chen¹, William A Craigo¹, Paul D van Poelje¹, Deidre A MacKenna¹, Edward E Cable¹, Paul A Rolzin¹, Patricia D Finn¹, Bert Chi¹, David L Linemeyer¹, Scott J Hecker¹, Mark D Erion¹.

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.

Entities: Chemical Disease Gene

Keywords: 5-(5-Hydroxy-isoxazol-3-yl)-furan-2-phosphonic acid; AMPK activator; hepatocytes; lipogenesis

Year: 2010 PMID： 24900234 PMCID： PMC4007905 DOI： 10.1021/ml100143q

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

30 in total

Review 1. The AMP-activated protein kinase--fuel gauge of the mammalian cell?

Authors: D G Hardie; D Carling
Journal: Eur J Biochem Date: 1997-06-01

2. Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay.

Authors: S P Davies; D Carling; D G Hardie
Journal: Eur J Biochem Date: 1989-12-08

3. Hypoglycaemic effect of AICAriboside in mice.

Authors: M F Vincent; M D Erion; H E Gruber; G Van den Berghe
Journal: Diabetologia Date: 1996-10 Impact factor: 10.122

Review 4. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer.

Authors: S Fogarty; D G Hardie
Journal: Biochim Biophys Acta Date: 2009-09-22

5. Stimulation of rat liver AMP-activated protein kinase by AMP analogues.

Authors: N Henin; M F Vincent; G Van den Berghe
Journal: Biochim Biophys Acta Date: 1996-06-04

6. Discovery and SAR development of thienopyridones: a class of small molecule AMPK activators.

Authors: Gang Zhao; Rajesh R Iyengar; Andrew S Judd; Barbara Cool; William Chiou; Lemma Kifle; Ernst Frevert; Hing Sham; Philip R Kym
Journal: Bioorg Med Chem Lett Date: 2007-04-10 Impact factor: 2.823

Review 7. Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity.

Authors: Neil B Ruderman; Asish K Saha; Edward W Kraegen
Journal: Endocrinology Date: 2003-09-18 Impact factor: 4.736

Review 8. AMPK: a key regulator of energy balance in the single cell and the whole organism.

Authors: D G Hardie
Journal: Int J Obes (Lond) Date: 2008-09 Impact factor: 5.095

9. Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes.

Authors: Qun Dang; Srinivas Rao Kasibhatla; K Raja Reddy; Tao Jiang; M Rami Reddy; Scott C Potter; James M Fujitaki; Paul D van Poelje; Jingwei Huang; William N Lipscomb; Mark D Erion
Journal: J Am Chem Soc Date: 2007-11-28 Impact factor: 15.419

Review 10. AMPK: an emerging drug target for diabetes and the metabolic syndrome.

Authors: Bei B Zhang; Gaochao Zhou; Cai Li
Journal: Cell Metab Date: 2009-05 Impact factor: 27.287

33 in total

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Journal: Tumour Biol Date: 2015-08-14

2. Novel substituted pyrazolone derivatives as AMP-activated protein kinase activators to inhibit lipid synthesis and reduce lipid accumulation in ob/ob mice.

Authors: Mei Zhang; Zhi-Fu Xie; Run-Tao Zhang; Da-Kai Chen; Min Gu; Shi-Chao Cui; Yang-Ming Zhang; Xin-Wen Zhang; Yan-Yan Yu; Jia Li; Fa-Jun Nan; Jing-Ya Li
Journal: Acta Pharmacol Sin Date: 2018-05-24 Impact factor: 6.150

Review 3. Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK) modulators and human diseases.

Authors: Sandeep Rana; Elizabeth C Blowers; Amarnath Natarajan
Journal: J Med Chem Date: 2014-08-28 Impact factor: 7.446

Review 4. AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance.

Authors: Daniel Garcia; Reuben J Shaw
Journal: Mol Cell Date: 2017-06-15 Impact factor: 17.970

5. Discovery of Pyridones As Oral AMPK Direct Activators.

Authors: Olivier Mirguet; Stéphane Sautet; Catherine-Anne Clément; Jérôme Toum; Frédéric Donche; Celine Marques; Emilie Rondet; Mathieu Pizzonero; Benjamin Beaufils; Yann Dudit; Pascal Huet; Lionel Trottet; Pascal Grondin; Jean-Marie Brusq; Eric Boursier; Yannick Saintillan; Edwige Nicodeme
Journal: ACS Med Chem Lett Date: 2013-05-17 Impact factor: 4.345