Ligands to peroxisome proliferator-activated receptors as therapeutic options for metabolic syndrome

Drug Discovery Today: Therapeutic Strategies

Volumn 2, Issue 2, 2005, Pages 165-169

  Liu, Yanfang ^a   Miller, Anne Reifel ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,2 DICHLORO 12 (4 CHLOROPHENYL)DODECANOIC ACID; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 5 (2,4 DIOXO 5 THIAZOLIDINYLMETHYL) 2 METHOXY N [4 (TRIFLUOROMETHYL)BENZYL]BENZAMIDE; ANTIDIABETIC AGENT; IMIGLITAZAR; LIGAND; LY 465608; MURAGLITAZAR; NAVEGLITAZAR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PIOGLITAZONE; PLACEBO; PLX 204; RAGAGLITAZAR; ROSIGLITAZONE; T 0903131; T 131; T 659; TESAGLITAZAR; TROGLITAZONE; UNCLASSIFIED DRUG; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID;

ARTICLE; CARBOHYDRATE METABOLISM; CLINICAL TRIAL; DISEASE MODEL; DRUG ACTIVITY; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG POTENCY; DRUG TARGETING; DYSLIPIDEMIA; EDEMA; HEMODILUTION; HUMAN; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; LIPID METABOLISM; LIVER TOXICITY; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PROTEIN LOCALIZATION; SIDE EFFECT;

EID: 22144477183     PISSN: 17406773     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ddstr.2005.05.015     Document Type: Review

References (40)

1. E.S. Ford et al. Increasing prevalence of the metabolic syndrome among U.S. adults Diabetes Care 27 2004 2444-2449
2. G.E. Duncan et al. Prevalence and trends of a metabolic syndrome phenotype among U.S. adolescents Diabetes Care 27 2004 2438-2443
3. B. Desvergne et al. Be fit or be sick: Peroxisome proliferator-activated receptors are down the road Mol. Endocrinol. 18 2004 1321-1332
4. J.M. Lehmann et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptorγ (PPARγ) J. Biol. Chem. 270 1995 12953-12956
5. Press Release: Warner-Lambert voluntarily discontinues the sale of Rezulin. 21 March (2000) (http://www.warner-lambert.com/press/ reslease.asp?release=109)
6. M. Diamant R.J. Heine Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence Drugs 63 2003 1373-1405
7. M.J. Ryan et al. PPARγ agonist rosiglitazone improves vascular function and lowers blood pressure in hypertensive transgenic mice Hypertension 43 2004 661-666
8. A. Raji et al. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients Diabetes Care 26 2003 172-178
9. K.J. Moore et al. Peroxisome proliferator-activated receptors in macrophage biology: Friend or foe? Curr. Opin. Lipidol. 12 2001 519-527
10. C. Duval et al. PPARα, fibrates, lipid metabolism and inflammation Arch. Mal. Coeur. 97 2004 665-672
11. Q.N. Diep et al. PPARα activator fenofibrate inhibits myocardial inflammation and fibrosis in angiotensin II-infused rats J. Mol. Cell. Cardiol. 36 2004 295-304
12. J.I. Kim et al. Bezafibrate improves hypertension and insulin sensitivity in humans Hypertension Res. 26 2003 307-313
13. M. Oron-Herman et al. Risk reduction therapy of syndrome X: Comparison of several treatments AJH 18 2005 372-378
14. N.L. Bodkin et al. The effects of K-111, a new insulin-sensitizer, on metabolic syndrome in obese pre-diabetic rhesus monkeys Horm. Metab. Res. 35 2003 617-624
15. Kowa Licenses Antidiabetic Drug from Roche. Regulatory/Business, Pharma Japan:1748, 4th June (2004)
16. S.A. Schafer et al. Biochemical and morphological effects of K-111, a peroxisome proliferator-activated receptors (PPAR) alpha activator, in non-human primates Biochem. Pharmacol. 68 2004 239-251
17. W.R. Oliver et al. A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport Proc. Natl. Acad. Sci. USA 98 2001 5306-5311
18. T. Tanaka et al. Activation of peroxisome proliferator-activated receptor δ induces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome Proc. Natl. Acad. Sci. 100 2003 15924-15929
19. Dressel, U. et al. (2003) The Peroxisome proliferator-activated receptorβ/δ agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Molecular Endocrinology 17, 2477-2493
20. J. Sakamoto et al. Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone Biochem. Biophys. Res. Commun. 278 2000 704-711
21. Press Release: Bristol-Myers Squibb Provides Regulatory Update for Muraglitazar and Abatacept. 23rd December (2004) (http://www.bms.com/news/press/data/fg_press_release_5269.html)
22. Press Release: Bristol-Myers Squibb Showcases Pipeline at Research and Development Overview Meeting. 17th November (2004) (http://www.bms.com/news/press/data/fg_press_release_5134.html)
23. Press Release: AstraZeneca Set to deliver top-tier financial performance through US marketing and R&D success. 2nd October (2003) (http://www.astrazeneca.com/pressrelease/687.aspx)
24. M. Prince et al. Efficacy of LY519818, a novel non-TZD, PPARγ-dominant α/γ dual agonist Diabetes 52 Suppl. 2 2004 A33
25. Press Release: Discontinuation of Development of Anti-Diabetic Agent TAK559. 30th March (2005) (http://www.takeda.co.jp/english/press/ 05033001.htm)
26. Press Release: Facts about Novo Nordisk's clinical trials with ragaglitazar. 26th July (2002) (http://www.novonordisk.com/press/news/ news.asp?s)
27. Faxwatch News Headlines. Merck ends Phase III program for investigational diabetes treatment MK-767; shares fall. 21st November (2003) (http://www.trustbasedmarketing.com/sm/news.1539/newsdetail.aspx)
28. K. Murakami et al. A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor α (PPARα) and PPARγ: Effect of PPARα activation on abnormal lipid metabolism in liver of Zucker fatty rats Diabetes 47 1998 1841-1847
29. K.G. Liu et al. Identification of a series of PPARγ/δ dual agonists via solid-phase parallel synthesis Bioorg. Med. Chem. Lett. 11 2001 2959-2962
30. J.M. Wallace et al. Effects of peroxisome proliferator-activated receptor α/δ agonists on HDL-cholesterol in vervet monkeys J. Lipid Res. 46 2005 1009-1016
31. Press release: Plexxikon and Wyeth Collaborate to Develop Novel Treatments for Diabetes and Metabolic Disorders. 28th October (2004) (http://www.plexxikon.com/release-102804.shtml)
32. PPAR pan-agonist fact sheet. Metabolic DisordersCardiovascular Disease. Plexxikon (July 2004)
33. Sternback, D.D. et al. (2005) Synthesis and crystal structure of a PPARpan agonist that delivers glycemic control and improved lipid profiles without weight gain. Keystone Symposia Abstract Book. Diabetes Mellitus (J3) (Abstract 439)
34. M.C. Lewis et al. The effects of a PPARα, PPARδ and PPARpanα/δ/γ agonists on diet-induced obesity in fat-fed AKR mice Diabetes 53 Suppl. 2 2004 A134
35. G.J. Etgen and N. Mantlo PPAR ligands for metabolic disorders Curr. Top. Med. Chem. 3 2003 1649-1661
36. G.J. Etgen et al. A tailored therapy for the metabolic syndrome. The dual peroxisome proliferator-activated receptor-α/γ agonist LY465608 ameliorates insulin resistance and diabetic hyperglyemia while improving cardiovascular risk factors in preclinical models Diabetes 51 2002 1083-1087
37. C. Knouff and J. Auwerx Peroxisome proliferator-activated receptor-γ calls for activation in moderation: Lessons from genetics and pharmacology Endocr. Rev. 25 2005 899-918
38. Y. Li et al. T0903131 (T131): A selective modulator of PPARγ Diabetes 53 Suppl. 2 2004 A157
39. P. Misra et al. PAT5A: A partial agonist of peroxisome proliferator-activated receptor γ is a potent antidiabetic thiazolidinedione yet weakly adipogenic J. Pharmacol. Exp. Ther. 306 2003 763-771
40. Vikramadithyan et al. Euglycemic and hypolipidemic activity of PAT5A: A unique thiazolidinedione with weak peroxisome proliferator activated receptor gamma activity Metabolism 49 2000 1417-1424