DRF 2655: A unique molecule that reduces body weight and ameliorates metabolic abnormalities

Obesity Research

Volumn 11, Issue 2, 2003, Pages 292-303

  Vikramadithyan, Reeba K ^a   Hiriyan, Jagadheshan ^a   Suresh, Juluri ^a   Gershome, Cynthia ^a   Babu, Ravi K ^a   Misra, Parimal ^a   Rajagopalan, Ramanujam ^a   Chakrabarti, Ranjan ^a  

^a DR REDDY'S LABORATORIES LTD   (India)

Author keywords

Hyperlipidemia; Peroxisome proliferator activated receptor alpha; Peroxisome proliferator activated receptor gamma; Type 2 diabetes

Indexed keywords

ANIMALIA;

ANTIDIABETIC AGENT; ANTILIPEMIC AGENT; ANTIOBESITY AGENT; CELL RECEPTOR; CHOLESTEROL; DRF 2655; FATTY ACID; FENOFIBRATE; HYBRID PROTEIN; OXAZINE DERIVATIVE; PROPIONIC ACID DERIVATIVE; TRANSCRIPTION FACTOR; TRIACYLGLYCEROL;

ADIPOCYTE; ANIMAL; ARTICLE; BIOSYNTHESIS; BLOOD; C57BL MOUSE; CELL DIFFERENTIATION; CELL LINE; CELL STRAIN 3T3; CYTOLOGY; DIABETES MELLITUS; DRUG EFFECT; DRUG POTENTIATION; ENZYMOLOGY; GENETIC TRANSFECTION; GENETICS; HAMSTER; HUMAN; LIVER; MALE; METABOLISM; MOUSE; MOUSE MUTANT; OBESITY; RAT; SYRIAN HAMSTER; TRANSACTIVATION; WEIGHT REDUCTION; ZUCKER RAT;

3T3 CELLS; ADIPOCYTES; ANIMALS; ANTI-OBESITY AGENTS; ANTILIPEMIC AGENTS; CELL DIFFERENTIATION; CELL LINE; CHOLESTEROL; CRICETINAE; DIABETES MELLITUS; FATTY ACIDS, NONESTERIFIED; HUMANS; HYPOGLYCEMIC AGENTS; LIVER; MALE; MESOCRICETUS; MICE; MICE, INBRED C57BL; MICE, OBESE; OBESITY; OXAZINES; PROCETOFEN; PROPIONIC ACIDS; RATS; RATS, ZUCKER; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECOMBINANT FUSION PROTEINS; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION FACTORS; TRANSFECTION; TRIGLYCERIDES; WEIGHT LOSS;

EID: 0042229358     PISSN: 10717323     EISSN: None     Source Type: Journal    
DOI: 10.1038/oby.2003.44     Document Type: Article

References (54)

1. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595-607.
2. DeFronzo RA, Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and artherosclerotic cardiovascular disease. Diabetes Care. 1991;14:173-94.
3. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998;98:2088-93.
4. Olefsky JM. Treatment of insulin resistance with peroxisome proliferator activated receptor gamma agonists. J Clin Invest. 2000;106:467-72.
5. Torra IP, Chinetti G, Duval C, Fruchart JC, Staels B. Peroxisome proliferator activated receptors: from transcriptional control to clinical practice. Curr Opin Lipidol. 2001;12:245-54.
6. Spiegelman BM. PPARγ: adipogenic regulator and thiazolidinediones receptor. Diabetes. 1998;47:507-14.
7. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000;405:421-4.
8. Canada reports 166 ADRs with Avandia. Scrip 2001;2668:23.
9. Knopp RH. Drug treatment of lipid disorders. N Engl J Med. 1999;341:498-511.
10. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527-50.
11. Guerre-Millo M, Gervois MP, Raspe E, et al. PPARα activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000;275:16638-42.
12. Chaput E, Saladin R, Silvestre M, Edgar AD. Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun. 2000;271:445-50.
13. Glaxo Wellcome Group. Use of agonists of peroxisome proliferator activated receptor alpha for treating obesity. WO9736579 1997.
14. Rami HK, Smith SA. Synthetic ligands for PPARγ: review of patent literature 1994-1999. Exp Opin Ther Patents. 2000;10:623-34.
15. Kopelman PG. Obesity as a medical problem. Nature. 2000;404:635-43.
16. Chaki S, Nakazato A. Recent advances in feeding suppressing agents: potential therapeutic strategy for the treatment of obesity. Expert Opin Ther Patents. 2001;11:1677-92.
17. Lefebvre AM, Peinado-Onsurbe J, Leitersdorf I, et al. Regulation of lipoprotein metabolism by thiazolidinediones occurs through a distinct but complementary mechanism relative to fibrates. Arterioscler Thromb Vasc Biol. 1997;17:1756-64.
18. Lohray BB, Lohray VB, Bajji AC, et al. (-)3-[4-[2-(Phenoxazin-10-yl) ethoxy]phenyl]-2-ethoxypropanoic acid [(-) DRF 2725]: a dual PPAR agonist with potent antihyperglycemic and lipid modulating activity. J Med Chem. 2001;44:2675-78.
19. Etgen GJ, Oldham BA, Johnson WT, et al. A tailored therapy for metabolic syndrome. Diabetes. 2002;51:1083-87.
20. Dahllof B, Ostling J, Wettesten M, et al. AZ 242, a novel di-hydro cinnamate derivative, shows PPARα and PPARγ mediated effects in vitro and in vivo. Diabetes 2001;50(Suppl 2):A122 (abstr).
21. Murukami K, Tabe K, Ide T, et al. A novel insulin sensitizer acts as a coligand for PPARα and PPARγ. Diabetes. 1998;47:1841-7.
22. Shinkai H. The chemical structure and pharmacological properties of a novel isoxazolidinedione insulin sensitizer, JTT-501. Nippon Rinsho. 2001;59:2207-10.
23. Chakrabarti R, Reeba KV, Suresh J, et al. (-) DRF 2725, a novel dual activator of PPARα and PPARγ with unique antidiabetic and hypolipidemic activity. Diabetes 2001; 50(Suppl 2):432P.
24. Harrity T, Chandrasena G, Chen C, et al. BMS-298585, a novel, uniquely balanced dual activator of PPARα and PPARγ shows robust lipid and glucose lowering effects in high fat diet induced hyperlipidemic insulin resistant hamsters. Diabetes 2002;51(Suppl 2):407P.
25. Borstel RV, Cardin S, Song X, et al. PN 2034: reversal of insulin resistance and attenuation of weight gain in mice with high-fat diet. Diabetes 2002;51(Suppl 2):586p.
26. Olney JW. Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate. Science. 1969;164:719-21.
27. Zhang Y, Scislowski PW, Prevelige R, Phaneuf S, Cincotta AH. Bromocryptine/SKF38393 treatment ameliorates dyslipidemia in ob/ob mice. Metabolism. 1999;48:1033-40.
28. Gallwitz WE, Jacoby GH, Ray PD, Lambeth DO. Purification and characterization of the isozymes of phosphoenolpyruvate carboxykinase from rabbit liver. Biochim Biophys Acta. 1988;964:36-45.
29. Vikramadithyan RK, Chakrabarti R, Misra P, et al. Euglycemic and hypolipidemic activity of PAT5A: a unique thiazolidinedione with weak PPARy activity. Metabolism. 2000;49:1417-24.
30. Bieber LL, Abraham T, Helmrath T. A rapid spectrophotometric method for carnitine palmitoyltransferase. Anal Biochem. 1972;50:509-18.
31. Bieber LL, Markwell MAK. Peroxisomal and microsomal carnitine acetyltransferase. Methods Enzymol. 1981;71:351-8.
32. Mittal B, Kurup R. Purification of clofibrate induced carnitine acetyltransferase from rat liver mitochondria. Biochim Biophys Acta. 1980;619:90-7.
33. Iverius PH, Lindqvist AMO. Preparation, characterization and measurement of lipoprotein lipase. Methods Enzymol. 1986;129:691-704.
34. Wang M, Wise SC, Leff T, Su TZ. Troglitazone, an antidiabetic agent, inhibits cholesterol biosynthesis through a mechanism independent of PPARγ. Diabetes. 1999;48:254-60.
35. Mukherjee R, Hoener PA, Jow L, et al. A selective PPARγ modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes. Mol Endocrinol. 2000;14:1425-33.
36. Canan KSS, Dardashti LJ, Cesario RM, et al. Synthesis of RXR specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells. J Med Chem. 1999;42:742-50.
37. Patel J, Miller E, Hu J, Graneth J. BRL 49653 improves glycemic control in NIDDM patients. Diabetes 1997;46(Suppl 1):0578p
38. Balfour JA, Plosker GL. Rosiglitazone. Drugs. 1999;57:921-30.
39. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkinson WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for PPARγ. J Biol Chem. 1995;270:12953-6.
40. Kliewer SA, Lenhard JM, Willsom TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds PPARγ and promotes adipocyte differentiation. Cell. 1995;83:813-9.
41. Assimacopoulos-Janet F, Jeanrenaud B. The hormonal and metabolic basis of experimental obesity. Clin Endocrinol Metabol. 1976;5:337-65.
42. Brown PJ, Chapman JM, Oplinger JA, Stuart LW, Willson TM, Wu Z. New derivatives are PPARα activators: useful for the treatment of a PPARα mediated disease, e.g. obesity, dyslipidemia, Alzheimer's disease or diabetes. WO200023407-A2 2000.
43. Fujiwara T, Wada M, Fukuda K. Characterization of CS-045, a new oral antidiabetic agent: II. Effect on glycemic control and pancreatic islet structure at a late stage of the diabetic syndrome in C57BL/Ks-db/db mice. Metabolism. 1991;40:1213-8.
44. Genuth SM, Przybylski RJ, Rosenberg DM. Insulin resistance in genetically obese, hyperglycemic mice. Endocrinology. 1971;88:1230-8.
45. Kobayashi M, Shigeta Y, Hirata Y, et al. Improvement of glucose tolerance in NIDDM by clofibrate. Randomized double blind study. Diabetes Care. 1988;11:495-9.
46. Ogawa S, Takeuchi K, Sugimura K, et al. Bezafibrate reduces blood glucose in type 2 diabetes mellitus. Metabolism. 2000;49:331-4.
47. Petit D, Bonnefis MT, Rey C. Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo and hyperlipidemic rats. Atherosclerosis. 1988;74:215-25.
48. Li X, Catalina F, Grundy SM, Patel S. Method to measure apolipoprotein B-48 and B-100 secretion rates in an individual mouse: evidence for a very rapid turnover of VLDL and preferential removal of B-48 relative to B-100 containing lipoproteins. J Lipid Res. 1996;37:210-20.
49. Staels B, Vu-Dac N, Kosykh V, et al. Fibrates down-regulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. J Clin Invest. 1996;97:705-12.
50. Schoonjans K, Peinado-Onsurbe J, Heyman R, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996;15:5336-48.
51. Goldberg IJ. Lipoprotein lipase and lipolysis. J Lipid Res. 1996;37:693-707.
52. Hoffmann A, Schmalz M, Leineweber M. Cholesterol lowering action on HOE 402 in the normolipidemic and hypercholesterolemic golden Syrian hamster. Biochim Biophys Acta. 1996;1299:95-102.
53. Schoonjans K, Steals B, Auwerx J. Role of peroxisome proliferator activated receptor in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res. 1996;37:907-25.
54. Dryer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992;68:879-87.