A potent and selective AMPK activator that inhibits de novo lipogenesis

ACS Medicinal Chemistry Letters

Volumn 1, Issue 9, 2010, Pages 478-482

  Gómez Galeno, Jorge E ^a,b   Dang, Qun ^a,c   Nguyen, Thanh H ^a   Boyer, Serge H ^a,d   Grote, Matthew P ^a   Sun, Zhili ^a   Chen, Mingwei ^a   Craigo, William A ^a   Van Poelje, Paul D ^a,e   MacKenna, Deidre A ^a,f   Cable, Edward E ^a,g   Rolzin, Paul A ^a,h   Finn, Patricia D ^a   Chi, Bert ^a   Linemeyer, David L ^a,i   Hecker, Scott J ^a,d   Erion, Mark D ^a,c  

^a Metabasis Therapeutics Inc   (United States)

^b Merck Research Laboratories ^*  (United States)

^c MERCK RESEARCH LABORATORIES   (United States)

^d Mpex Pharmaceuticals Inc   (United States)

^e PFIZER INC   (United States)

^f REGULUS THERAPEUTICS   (United States)

^g Ferring Pharmaceuticals AS   (Denmark)

^h Takeda San Diego Inc   (United States)

ⁱ Senomix Inc   (United States)

Author keywords

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

Indexed keywords

5 (5 HYDROXY ISOXAZOL 3 YL) FURAN 2 PHOSPHONIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ACTIVATOR; PHOSPHONIC ACID DERIVATIVE; PRODRUG; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG SCREENING; ENZYME ACTIVATION; HYPERLIPIDEMIA; LIPOGENESIS; LIVER CELL; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; RAT; WESTERN BLOTTING;

ANIMALIA;

EID: 78650224772     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml100143q     Document Type: Article

References (31)

1. Nathan, D. M.; Buse, J. B.; Davidson, M. B.; Ferrannini, E.; Holman, R. R.; Sherwin, R.; Zinman, B. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care 2009, 32, 193-203
2. Zhang, B. B.; Zhou, G.; Liu, C. AMPK: An emerging drug target for diabetes and the metabolic syndrome Cell Metab. 2009, 9, 407-416
3. Hardie, D. G. AMP-activated protein kinase as a drug target Annu. Rev. Pharmacol. Toxicol. 2007, 47, 185-210
4. Hardie, D. G.; Carling, D. Cellular energy sensing and signaling by AMP-activated protein kinase Cell Biochem. Biophys. 2007, 47, 332-347
5. Hardie, D. G.; Carling, D. The AMP-activated protein kinase-Fuel gauge of the mammalian cell? Eur. J. Biochem. 1997, 246, 259-273
6. Winder, W. W.; Hardie, D. G. AMP-activated protein kinase, a metabolic master switch: Possible roles in type 2 diabetes Am. J. Physiol. 1999, 277 (1 Part 1) E1-E10
7. Hardie, D. G. AMPK: A key regulator of energy balance in the single cell and the whole organism Int. J. Obes. (London) 2008, 32 (Suppl. 4) S7-S12
8. Erion, M. D.; Dang, Q.; Reddy, M. R.; Kasibhatla, S. R.; Huang, J.; Lipscomb, W. N.; van Poelje, P. D. Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity J. Am. Chem. Soc. 2007, 129, 15480-15490
9. Dang, Q.; Kasibhatla, S. R.; Reddy, K. R.; Jiang, T.; Reddy, M. R.; Potter, S. C.; Fujitaki, J. M.; van Poelje, P. D.; Huang, J.; Lipscomb, W. N.; Erion, M. D. 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 J. Am. Chem. Soc. 2007, 129, 15491-15502
10. Vincent, M. F.; Erion, M. D.; Gruber, H. E.; Van den Berghe, G. Hypoglycaemic effect of AICAriboside in mice Diabetologia 1996, 39, 1148-1155
11. Henin, N.; Vincent, M. F.; Van den Berghe, G. Stimulation of rat liver AMP-activated protein kinase by AMP analogues Biochim. Biophys. Acta 1996, 1290, 197-203
12. Guigas, B.; Sakamoto, K.; Taleux, N.; Reyna, S. M.; Musi, N.; Viollet, B.; Hue, L. Beyond AICA ribosida: In search of new specific AMP-activated protein kinase activators IUBMB Life 2009, 61, 18-26
13. Fogarty, S.; Hardie, D. G. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer Biochim. Biophys. Acta 2010, 1804, 581-591
14. Taylor, E. B.; An, D.; Kramer, H. F.; Yu, H.; Fujii, N. L.; Roeckl, K. S.; Bowles, N.; Hirshman, M. F.; Xie, J.; Feener, E. P.; Goodyear, L. J. Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle J. Biol. Chem. 2008, 283, 9787-9796
15. Ho, R. C.; Fujii, N; Witters, L. A.; Hirshman, M. F.; Goodyear, L. J. Dissociation of AMP-activated protein kinase and p38 mitogen-activated protein kinase signaling in skeletal muscle Biochem. Biophys. Res. Commun. 2007, 362, 354-359 (Pubitemid 47332415)
16. Pold, R.; Jensen, L. S.; Jessen, N.; Buhl, E. S.; Schmitz, O.; Flyvbjerg, A.; Fujii, N.; Goodyear, L. J.; Gotfredsen, C. F.; Brand, C. L.; Lund, S. Long-term AICAR administration and exercise prevents diabetes in ZDF rats Diabetes 2005, 54, 928-934
17. Zhou, G.; Myers, R.; Li, Y.; Chen, Y.; Shen, X.; Fenyk-Melody, J.; Wu, M.; Ventre, J.; Doebber, T.; Fujii, N.; Musi, N.; Hirshman, M. F.; Goodyear, L. J.; Moller, D. E. Role of AMP-activated protein kinase in mechanism of metformin action J. Clin. Invest. 2001, 108, 1167-1174
18. LeBrasseur, N. K.; Kelly, M.; Tsao, T. S.; Farmer, S. R.; Saha., A. K.; Ruderman, N. B.; Tomas, E. Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues Am. J. Physiol. Endocrinol. Metab. 2006, 291, E175-E181
19. Saha, A. K.; Avilucea, P. R.; Ye, J. M.; Assifi, M. M.; Kraegen, E. W.; Ruderman, N. B. Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo Biochem. Biophys. Res. Commun. 2004, 314, 580-585
20. Cool, B.; Zinker, B.; Chiou, W.; Kifle, L.; Cao, N.; Perham, M.; Dickinson, R.; Adler, A.; Gagne, G.; Iyengar, R.; Zhao, G.; Marsh, K.; Kym, P.; Jung, P.; Camp, H. S.; Frevert, E. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome Cell Metab. 2006, 3, 403-416
21. Zhao, G.; Iyengar, R. R.; Judd, A. S.; Cool, B.; Chiou, W.; Kifle, L.; Frevert, E.; Sham, H.; Kym, P. R. Discovery and SAR development of thienopyridones: a class of small molecule AMPK activators Bioorg. Med. Chem. Lett. 2007, 17, 3254-3257
22. Inouye, Y.; Taguchi., M.; Hashimoto, H. N-Alkylation of Imides with O-Alkylisourea under Neutral Conditions Synthesis 1986, 1986, 332-334
23. Dudley, G. B.; Takaki, K. S.; Cha, D. D.; Danheiser, R. L. Total Synthesis of (-)-Asochlorin via a Cyclobutenone-Based Benzannulation Org. Lett. 2000, 2, 3407-3410
24. Davies, S. P.; Carling, D.; Hardie, D. G. 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 Eur. J. Biochem. 1989, 186, 123-128
25. Carling, D.; Zammit, V. A.; Hardie, D. G. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis FEBS Lett. 1987, 223, 217-222
26. Ruderman, N. B.; Saha, A. K.; Kraegen, E. W. Minireview: Malonyl CoA, AMP-activated protein kinase, and adiposity Endocrinology 2003, 144, 5166-5171
27. Hecker, S. J.; Erion, M. D. Prodrugs of phosphates and phoshonates J. Med. Chem. 2008, 51 (8) 2328-2345
28. Folch, J.; Lees, M.; Stanley, G. H. S. A simple method for the isolation and purification of total lipids from animal tissues J. Biol. Chem. 1957, 226, 497-509
29. Nguyen, P. H.; Le, T. V. T.; Kang, H. W.; Chae, J.; Kim, S. K.; Kwon, K.; Seo, D. B.; Lee, S. J.; Oh, W. K. AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect Bioorg. Med. Chem. Lett. 2010, 20, 4128-4131
30. Guh, J.-H.; Chang, W.-L.; Yang, J.; Lee, S.-L.; Wei, S.; Wang, D.; Kulp, S. K.; Chen, C.-S. Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators J. Med. Chem. 2010, 53, 2552-2561
31. Pang, T.; Zhang, Z.-S.; Gu, M.; Qiu, B.-Y.; Yu, L.-F.; Cao, P.-R.; Shao, W.; Su, M.-B.; Li, J.-Y.; Nan, F.-J.; Li, J. Small molecule antagonizes autoinhibition and activates AMP-activated protein kinase in cells J. Biol. Chem. 2008, 283, 16051-16060