MBX-102/JNJ39659100, a novel non-TZD selective partial PPAR-γ agonist lowers triglyceride independently of PPAR-α activation

PPAR Research

Volumn , Issue , 2009, Pages

  Gregoire, Francine M ^a   Chandalia, Apurva ^a   Clarke, Holly J ^a,b   Clemens, L Edward ^a   Pandey, Bindu ^a   Vicena, Vic ^a   Lee, Paul ^a   Lavan, Brian E ^a  

^a Metabolex Inc   (United States)

^b GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HALOFENATE; METAGLIDASEN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; PIRINIXIC ACID; ROSIGLITAZONE; TRIACYLGLYCEROL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DIABETES MELLITUS; DRUG MECHANISM; DRUG STRUCTURE; GENE EXPRESSION; HUMAN; HUMAN CELL; IN VIVO STUDY; KNOCKOUT MOUSE; LIVER CELL; LIVER WEIGHT; MALE; MOUSE; NONHUMAN; RAT; TRIACYLGLYCEROL BLOOD LEVEL; ZUCKER DIABETIC FATTY RAT;

EID: 65649104489     PISSN: 16874757     EISSN: 16874765     Source Type: Journal    
DOI: 10.1155/2009/706852     Document Type: Article

References (54)

1. Feige J. N., Gelman L., Michalik L., Desvergne B., Wahli W., From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions Progress in Lipid Research 2006 45 2 120 159 (Pubitemid 43248732)
2. Michalik L., Auwerx J., Berger J. P., International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors Pharmacological Reviews 2006 58 4 726 741
3. Kersten S., Peroxisome proliferator activated receptors and lipoprotein metabolism PPAR Research 2008 2008 11 (Pubitemid 350243189)
4. Staels B., Dallongeville J., Auwerx J., Schoonjans K., Leitersdorf E., Fruchart J.-C., Mechanism of action of fibrates on lipid and lipoprotein metabolism Circulation 1998 98 19 2088 2093 (Pubitemid 28512236)
5. Sprecher D. L., Lipids, lipoproteins, and peroxisome proliferator activated receptor- The American Journal of Cardiology 2007 100 11, supplement 1 S20 S24 (Pubitemid 350161784)
6. Sprecher D. L., Massien C., Pearce G., Triglyceride: high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor agonist Arteriosclerosis, Thrombosis, and Vascular Biology 2007 27 2 359 365 (Pubitemid 46143052)
7. Reilly S. M., Lee C.-H., PPAR as a therapeutic target in metabolic disease FEBS Letters 2008 582 1 26 31 (Pubitemid 350297247)
8. Madrazo J. A., Kelly D. P., The PPAR trio: regulators of myocardial energy metabolism in health and disease Journal of Molecular and Cellular Cardiology 2008 44 6 968 975
9. Schmuth M., Jiang Y. J., Elias P. M., Feingold K. R., Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology Journal of Lipid Research 2008 49 3 499 509
10. Iwashita A., Muramatsu Y., Yamazaki T., Neuroprotective efficacy of the peroxisome proliferator-activated receptor -selective agonists in vitro and in vivo Journal of Pharmacology and Experimental Therapeutics 2007 320 3 1087 1096 (Pubitemid 46294065)
11. Peters J. M., Hollingshead H. E., Gonzalez F. J., Role of peroxisome-proliferator-activated receptor / (PPAR / ) in gastrointestinal tract function and disease Clinical Science 2008 115 3-4 107 127
12. Willson T. M., Cobb J. E., Cowan D. J., The structure-activity relationship between peroxisome proliferator-activated receptor agonism and the antihyperglycemic activity of thiazolidinediones Journal of Medicinal Chemistry 1996 39 3 665 668 (Pubitemid 26065821)
13. Deeg M. A., Tan M. H., Pioglitazone versus rosiglitazone: effects on lipids, lipoproteins, and apolipoproteins in head-to-head randomized clinical studies PPAR Research 2008 2008 6
14. Bavirti S., Ghanaat F., Tayek J. A., Peroxisome proliferator-activated receptor-gamma agonist increases both low-density lipoprotein cholesterol particle size and small high-density lipoprotein cholesterol in patients with type 2 diabetes independent of diabetic control Endocrine Practice 2003 9 6 487 493
15. Rubenstrunk A., Hanf R., Hum D. W., Fruchart J.-C., Staels B., Safety issues and prospects for future generations of PPAR modulators Biochimica et Biophysica Acta 2007 1771 8 1065 1081 (Pubitemid 47208546)
16. Yang T., Soodvilai S., Renal and vascular mechanisms of thiazolidinedione-induced fluid retention PPAR Research 2008 2008 8
17. Shearer B. G., Billin A. N., The next generation of PPAR drugs: do we have the tools to find them? Biochimica et Biophysica Acta 2007 1771 8 1082 1093 (Pubitemid 47202036)
18. Grey A., Skeletal consequences of thiazolidinedione therapy Osteoporosis International 2008 19 2 129 137
19. Fonseca V., Effect of thiazolidinediones on body weight in patients with diabetes mellitus The American Journal of Medicine 2003 115 8, supplement 1 42 48 (Pubitemid 37532891)
20. Zhang F., Lavan B. E., Gregoire F. M., Selective modulators of PPAR- activity: molecular aspects related to obesity and side-effects PPAR Research 2007 2007 7
21. Nesto R. W., Bell D., Bonow R. O., Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association Diabetes Care 2004 27 1 256 263 (Pubitemid 38196741)
22. Lincoff A. M., Wolski K., Nicholls S. J., Nissen S. E., Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials The Journal of the American Medical Association 2007 298 10 1180 1188 (Pubitemid 47403104)
23. Nissen S. E., Wolski K., Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes The New England Journal of Medicine 2007 356 24 2457 2471 (Pubitemid 46919772)
24. Lazarenko O. P., Rzonca S. O., Hogue W. R., Swain F. L., Suva L. J., Lecka-Czernik B., Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone Endocrinology 2007 148 6 2669 2680 (Pubitemid 46984815)
25. Rzonca S. O., Suva L. J., Gaddy D., Montague D. C., Lecka-Czernik B., Bone is a target for the antidiabetic compound rosiglitazone Endocrinology 2004 145 1 401 406 (Pubitemid 38094536)
26. Sottile V., Seuwen K., Kneissel M., Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone) Calcified Tissue International 2004 75 4 329 337 (Pubitemid 40064235)
27. Meier C., Kraenzlin M. E., Bodmer M., Jick S. S., Jick H., Meier C. R., Use of thiazolidinediones and fracture risk Archives of Internal Medicine 2008 168 8 820 825
28. Schwartz A. V., TZDs and bone: a review of the recent clinical evidence PPAR Research 2008 2008 6
29. Balint B. L., Nagy L., Selective modulators of PPAR activity as new therapeutic tools in metabolic diseases Endocrine, Metabolic and Immune Disorders Drug Targets 2006 6 1 33 43 (Pubitemid 43796712)
30. Carmona M. C., Louche K., Lefebvre B., S 26948: a new specific peroxisome proliferator-activated receptor modulator with potent antidiabetes and antiatherogenic effects Diabetes 2007 56 11 2797 2808 (Pubitemid 350044924)
31. Einstein M., Akiyama T. E., Castriota G. A., The differential interactions of peroxisome proliferator-activated receptor ligands with Tyr473 is a physical basis for their unique biological activities Molecular Pharmacology 2008 73 1 62 74 (Pubitemid 350294197)
32. Gelman L., Feige J. N., Desvergne B., Molecular basis of selective PPAR modulation for the treatment of type 2 diabetes Biochimica et Biophysica Acta 2007 1771 8 1094 1107 (Pubitemid 47214561)
33. Chang F., Jaber L. A., Berlie H. D., OConnell M. B., Evolution of peroxisome proliferator-activated receptor agonists Annals of Pharmacotherapy 2007 41 6 973 983 (Pubitemid 46917624)
34. Aronow W. S., Harding P. R., Khursheed M., Vangrow J. S., Papageorges N. P., Effect of halofenate on serum uric acid Clinical Pharmacology and Therapeutics 1973 14 3 371 373
35. Aronow W. S., Harding P. R., Khursheed M., Vangrow J. S., Papageorges N. P., Mays J., Effect of halofenate on serum lipids Clinical Pharmacology and Therapeutics 1973 14 3 358 365
36. Feldman E. B., Gluck F. B., Carter A. C., Effects of halofenate on glucose tolerance in patients with hyperlipoproteinemia Journal of Clinical Pharmacology 1978 18 5-6 241 248 (Pubitemid 8384291)
37. Krut L. H., Seftel H. C., Joffe B. I., Comparison of clofibrate with halofenate in diabetics with hyperlipidaemia South African Medical Journal 1977 51 11 348 352 (Pubitemid 8059986)
38. Allen T., Zhang F., Moodie S. A., Halofenate is a selective peroxisome proliferator-activated receptor modulator with antidiabetic activity Diabetes 2006 55 9 2523 2533
39. Trinder P., Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen Journal of Clinical Pathology 1969 22 2 158 161
40. Stumvoll M., Goldstein B. J., van Haeften T. W., Type 2 diabetes: principles of pathogenesis and therapy The Lancet 2005 365 9467 1333 1346 (Pubitemid 40501297)
41. Campbell I. W., The clinical significance of PPAR gamma agonism Current Molecular Medicine 2005 5 3 349 363 (Pubitemid 40663140)
42. Waugh J., Keating G. M., Plosker G. L., Easthope S., Robinson D. M., Pioglitazone: a review of its use in type 2 diabetes mellitus Drugs 2006 66 1 85 109 (Pubitemid 43144963)
43. Remick J., Weintraub H., Setton R., Offenbacher J., Fisher E., Schwartzbard A., Fibrate therapy: an update Cardiology in Review 2008 16 3 129 141
44. Duriez P., Mechanisms of actions of statins and fibrates Therapie 2003 58 1 5 14
45. Goldberg R. B., Kendall D. M., Deeg M. A., A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia Diabetes Care 2005 28 7 1547 1554 (Pubitemid 40923063)
46. Rosenstock J., Flores-Lozano F., Schartz S., Gonzalez-Galvez G., Karpf D., MBX-102: a novel non-TZD insulin sensitizer that improves glycemic control without causing edema or weight gain in patients with type 2 diabetes (T2DM) on concomitant insulin therapy Diabetes 2005 54 supplement 1. abstract no. 44-OR
47. Aronow W. S., Vicario M. D., Moorthy K., King J., Vawter M., Papageorges N. P., Long term efficacy of halofenate on serum triglyceride levels Current Therapeutic Research, Clinical and Experimental 1975 18 6 855 861
48. Dujovne C. A., Azarnoff D. L., Huffman D. H., Pentikinen P., Hurwitz A., Shoeman D. W., One year trials with halofenate, clofibrate, and placebo Clinical Pharmacology and Therapeutics 1976 19 3 352 359
49. Dujovne C. A., Azarnoff D. L., Pentikainen P., Manion C., Hurwitz A., Hassanein K., A two year crossover therapeutic trial with halofenate and clofibrate The American Journal of the Medical Sciences 1976 272 3 277 284 (Pubitemid 8033554)
50. Patsouris D., Reddy J. K., Mller M., Kersten S., Peroxisome proliferator-activated receptor mediates the effects of high-fat diet on hepatic gene expression Endocrinology 2006 147 3 1508 1516 (Pubitemid 43244386)
51. Staels B., Vu-Dac N., Kosykh V. A., Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates The Journal of Clinical Investigation 1995 95 2 705 712
52. Sakamoto J., Kimura H., Moriyama S., Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone Biochemical and Biophysical Research Communications 2000 278 3 704 711
53. Qin S., Liu T., Kamanna V. S., Kashyap M. L., Pioglitazone stimulates apolipoprotein A-I production without affecting HDL removal in HepG2 cells: involvement of PPAR- Arteriosclerosis, Thrombosis, and Vascular Biology 2007 27 11 2428 2434 (Pubitemid 350203960)
54. Cenedella R. J., Crouthamel W. G., Halofenate and clofibrate: mechanism of hypotriglyceridemic action in the rat Journal of Lipid Research 1976 17 2 156 166