Discovery and development of selective PPARγ modulators as safe and effective antidiabetic agents

Bibliography

• Wild S, Roglic G, Green A, Global prevelance of diabetes; Estimates for year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53
   PubMed Web of Science ®Google Scholar
• Semple RK, Chatterjee VKK, O'Rahilly S. PPAR-gamma and human metabolic disease. J Clin Invest 2006;116:581-9
   PubMed Web of Science ®Google Scholar
• Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-35
   PubMed Web of Science ®Google Scholar
• Seedorf U, Assmann G. The role of PPAR-alpha in obesity. Nutr Metab Cardiovasc Dis 2001;11:189-94
   PubMed Web of Science ®Google Scholar
• Oliver WR, Shenk JL, Snaith MR, A selective peroxisome proliferator-activated receptor d agonist promotes reverse cholesterol transport. Proc Natl Acad Sci USA 2001;98:5306-11
   PubMed Web of Science ®Google Scholar
• Wilson TM, Brown PJ, Sternbach DD, The PPARs: from orphan receptors to drug discovery. J Med Chem 2000;43:527-50
   PubMed Web of Science ®Google Scholar
• Vidal-puig AJ, Considine RV, Jimenez-linan M, Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest 1997;99:2416-22
   PubMed Web of Science ®Google Scholar
• Henry RR. Thiazolidinediones. Endocrinol Metab Clin North Am 1997;26:553-73
   PubMed Web of Science ®Google Scholar
• Guan Y, Hao C, Cha DR, Thiazolidinediones expand body fluid volume through PPAR-gamma stimulation of ENaC-mediated renal salt absorption. Nat Med 2005;11:861-6
   PubMed Web of Science ®Google Scholar
• Werner AL, Travaglini MT. A review of rosiglitazone in type 2 diabetes mellitus. Pharmacotherapy 2001;21:1082-99
   PubMed Web of Science ®Google Scholar
• Mori Y, Murakawa T, Okada K, Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care 1999;22:908-12
   PubMed Web of Science ®Google Scholar
• Hirose H, Kawai T, Yamamoto Y, Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metabolism 2002;51:314-7
   PubMed Web of Science ®Google Scholar
• Wilding J. Thiazolidinediones, Insulin resistance and obesity: finding a balance. Int J Clin Pract 2006;60:1272-80
   PubMed Web of Science ®Google Scholar
• Mudaliar S, Chang AR, Henry RR. Thiazolidinediones, peripheral edema, and Type 2 diabetes: incidence, pathophysiology, and clinical implications. Endocr Pract 2003;9:406-16
   PubMedGoogle Scholar
• Page RL, Gozansky WS, Ruscin JM. Possible exacerbation associated with rosiglitazone: case report and literature review. Pharmacotherapy 2003;23:945-54
   PubMed Web of Science ®Google Scholar
• Shearer BG, Billin AN. The next generation of PPAR drugs: do we have the tools to find them? Biochem Biophy Acta 2007;1771:1082-93
   PubMed Web of Science ®Google Scholar
• Ali AA, Weinstien RS, Stewart SA, Rosiglitazone causes bone loss in mice by suppressing osteoblast and bone formation. Endocrinology 2005;146:1226-35
   PubMed Web of Science ®Google Scholar
• Kahn S, Zinman B, Lachin J, Rosiglitazone-associated fractures in type 2 diabetes. An analysis from a diabetes outcome progression trial (ADOPT). Diabetes Care 2008;31:845-51
   PubMed Web of Science ®Google Scholar
• Home PD, Pocock SJ, Beck-Nielsen H, Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009;373:2125-35
   PubMed Web of Science ®Google Scholar
• Barnett AH. Redefining the role of thiazolidinediones in the management of type 2 diabetes. Vasc Health Risk Manag 2009;5:141-51
   PubMedGoogle Scholar
• Hofmannn CA, Colca JR. New oral thiazolidinediones antidiabetic agents act as insulin sensitizers. Diabetes Care 1992;15:1075-8
   PubMed Web of Science ®Google Scholar
• Kletzien RF, Clarke SD, Ulrich RG. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol 1992;41:393-8
   PubMed Web of Science ®Google Scholar
• Kletzien RF, Foellmi LA, Harris PK, Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 1992;42:558-62
   PubMed Web of Science ®Google Scholar
• Dreyer C, Krey G, Keller H, Control of the peroxisomal b-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992;68:879-87
   PubMed Web of Science ®Google Scholar
• Lehmann JM, Moore LB, Smith-Oilver TA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor (PPAR). J Biol Chem 1995;270:12953-6
   PubMed Web of Science ®Google Scholar
• Willson TM, Cobb JE, Cowan DJ, The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem 1996;39:665-8
   PubMed Web of Science ®Google Scholar
• Berger J, Bailey P, Biswas C, Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology 1996;137:4189-95
   PubMed Web of Science ®Google Scholar
• Nobuo C, Momose Y. Peroxisome proliferator-activated receptor-gamma agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem 2008;8:1483-507
   PubMed Web of Science ®Google Scholar
• Rubenstrunk A, Hanf R, Hum DW, Safety issues and prospects for future generations of PPAR modulators. Biochim Biophys Acta 2007;1771:1065-81
   PubMed Web of Science ®Google Scholar
• Cock TA, Houten SM, Auwrex J. Peroxisome proliferator-activated receptor-gamma: too much of a good thing causes harm. EMBO Rep 2004;5:142-7
   PubMed Web of Science ®Google Scholar
• Kubota N, Terauchi Y, Miki H, PPAR-gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 1999;4:597-609
   PubMed Web of Science ®Google Scholar
• Miles PDG, Barak Y, He W, Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency. J Clin Invest 2000;105:287-92
   PubMed Web of Science ®Google Scholar
• Deeb SS, Fajas L, Nemoto M, A pro12Ala substitution in PPAR-gamma2 associated with decreased receptor activity lower body mass index and improved insulin sensitivity. Nat Genet 1998;20:284-7
   PubMed Web of Science ®Google Scholar
• Savage DB, Tan GD, Acerini CL, Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes 2003;52:910-7
   PubMed Web of Science ®Google Scholar
• Zhang F, Lavan BE, Gregoire FM. Selective modulators of PPAR-gamma activity: molecular aspects related to obesity and side-effects. PPAR Res 2007; 2007:1-7
   Google Scholar
• Rocchi S, Picard F, Vamecq J, A unique PPAR-gamma ligand with potent insulin-sensitizing yet weak adipogenic activity. Mol Cell 2001;8:737-47
   PubMed Web of Science ®Google Scholar
• Feldman PL, Lambert MH, Henke BR. PPAR- modulators and PPAR- pan agonists for metabolic diseases: The next generation of drugs targeting peroxisome proliferator-activated receptors? Curr Top Med Chem 2008;8:728-49
   PubMed Web of Science ®Google Scholar
• Shang Y, Hu X, Direnzo J, Co-factor dynamics and sufficiency in estrogen receptor regulated transcription. Cell 2000;103:843-52
   PubMed Web of Science ®Google Scholar
• Miller AR, Etgen GJ. Novel peroxisome proliferator-activated receptor ligands for type 2 diabetes and the metabolic syndrome. Expert Opin Investig Drugs 2003;12:1489-500
   PubMed Web of Science ®Google Scholar
• Cho MC, Lee K, Paik S, Peroxisome proliferators-activated receptor (PPAR) modulators and metabolic disorders. PPAR Res 2008;2008:1-14
   Google Scholar
• Brzozowski AM, Pike AC, Dauter Z, Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997;389:753-8
   PubMed Web of Science ®Google Scholar
• Einstein M, Akiyama TE, Castriota GA, The differential interaction of peroxisome proliferator-activated receptor gamma ligands with Tyr473 is a physical basis for their unique biological activities. Mol Pharmacol 2008;73:62-74
   PubMed Web of Science ®Google Scholar
• Motani A, Wang Z, Weiszmann J, INT131: a selective modulator of PPAR-gamma. J Mol Biol 2009;386:1301-11
   PubMed Web of Science ®Google Scholar
• Burgermeister E, Schnoebelen A, Flament A, A novel partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) recruits PPAR-gamma-coactivator-1alpha, prevents triglyceride accumulation, and potentiates insulin signaling in vitro. Mol Endocrinol 2006;20:809-30
   PubMed Web of Science ®Google Scholar
• Bruning JB, Chalmers MJ, Prasad S, Partial agonists activate PPAR-gamma using a helix 12 independent mechanism. Structure 2007;15:1258-71
   PubMed Web of Science ®Google Scholar
• Elbrecht A, Chen Y, Adams A, L-764406 is a partial agonist of human peroxisome proliferator-activated receptor gamma. The role of Cys313 in ligand binding. J Biol Chem 1999;274:7913-22
   PubMed Web of Science ®Google Scholar
• Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000;14:121-41
   PubMed Web of Science ®Google Scholar
• Berger JP, Petro AE, Macnaul KL, Distinct properties and advantages of a novel peroxisome proliferator-activated protein g selective modulator. Mol Endocrinol 2003;17:662-76
   PubMed Web of Science ®Google Scholar
• Guan HP, Ishizuka T, Chui PC, Corepressors selectively control the transcriptional activity of PPAR-gamma in adipocytes. Genes Dev 2005;19:453-61
   PubMed Web of Science ®Google Scholar
• Yu S, Reddy JK. Transcription coactivators for peroxisome proliferator-activated receptors. Biochim Biophys Acta 2007;1771:936-51
   PubMed Web of Science ®Google Scholar
• Yu C, Markan K, Temple KA, The nuclear receptor corepressors NCoR and SMRT decrease peroxisome proliferator-activated receptor gamma transcriptional activity and repress 3T3–L1 adipogenesis. J Biol Chem 2005;280:13600-05
   PubMed Web of Science ®Google Scholar
• Cohen RN. Nuclear receptor corepressors and PPAR-gamma. Nucl Recept Signal 2006;4:1-4
   Google Scholar
• Stephen CB, Pershadsingh HA, Ho CI, Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-gamma–modulating activity. Hypertension 2004;43:993-1002
   PubMed Web of Science ®Google Scholar
• Schupp M, Clemenz M, Gineste R, Molecular characterization of new selective peroxisome proliferator-activated receptor gamma modulators with angiotensin receptor blocking activity. Diabetes 2005;54:3442-52
   PubMed Web of Science ®Google Scholar
• Allen T, Zhang F, Moodie SA, Halofenate is a selective peroxisome proliferator-activated receptor gamma modulator with antidiabetic activity. Diabetes 2006;55:2523-33
   PubMed Web of Science ®Google Scholar
• Oberfield JL, Collins JL, Holmes CP, A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation. Proc Natl Acad Sci USA 1999;96:6102-06
   PubMed Web of Science ®Google Scholar
• Fujimura T, Sakuma H, Konishi S, FK614, a novel peroxisome proliferator-activated receptor gamma modulator, induces differential transactivation through a unique ligand-specific interaction with transcriptional coactivators. J Pharmacol Sci 2005;99:342-52
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Oike Y, Kamon J, Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. Nat Genet 2002;30:221-6
   PubMed Web of Science ®Google Scholar
• Picard F, Gehin M, Annicotte JS, SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 2002;111:931-41
   PubMed Web of Science ®Google Scholar
• Coste A, Louet JF, Lagouge M, The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1alpha. Proc Natl Acad Sci USA 2008;105:17187-92
   PubMed Web of Science ®Google Scholar
• Handschin C, Spiegelman BM. Peroxisome proliferator activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 2006;27:728-35
   PubMed Web of Science ®Google Scholar
• Gregoire FM, Zhang F, Clarke HJ, MBX-102/JNJ39659100, a novel peroxisome proliferator-activated receptor-ligand with weak transactivation activity retains antidiabetic properties in the absence of weight gain and edema. Mol Endocrinol 2009;23:975-88
   PubMed Web of Science ®Google Scholar
• Puigserver P, Adelmant G, Wu Z, Activation of PPAR-gamma coactivator-1 through transcription factor docking. Science 1999;286:1368-71
   PubMed Web of Science ®Google Scholar
• Lin J, Handschin C, Spiegelman B. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005;1:361-70
   PubMed Web of Science ®Google Scholar
• Ge K, Guermah M, Yuan CX, Transcription coactivator TRAP220 is required for PPAR- gamma 2-stimulated adipogenesis. Nature 2002;417:563-7
   PubMed Web of Science ®Google Scholar
• Carmona MC, Louche K, Lefebvre B, S26948: a new specific peroxisome proliferator activated receptor gamma modulator with potent antidiabetes and antiatherogenic effects. Diabetes 2007;56:2797-808
   PubMed Web of Science ®Google Scholar
• Kim KR, Lee JH, Kim SJ, KR-62980: a novel peroxisome proliferator-activated receptor gamma agonist with weak adipogenic effects. Biochem Pharmacol 2006;72:446-54
   PubMed Web of Science ®Google Scholar
• Feige JN, Gelman L, Rossi D, The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J Biol Chem 2007;282:19152-66
   PubMed Web of Science ®Google Scholar
• Stanley TB, Leesnitzer LM, Montana VG, Subtype specific effects of peroxisome proliferator-activated receptor ligands on corepressor affinity. Biochemistry 2003;42:9278-87
   Google Scholar
• Liu W, Liu K, Wood HB, Discovery of a peroxisome proliferator activated receptor-gamma (PPAR-gamma) modulator with balanced PPAR-alpha activity for the treatment of type 2 diabetes and dyslipidemia. J Med Chem 2009;52:4443-53
   PubMed Web of Science ®Google Scholar
• Kim MK, Chae YN, Kim HS, PAR-1622 is a selective peroxisome proliferator-activated receptor gamma partial activator with preserved antidiabetic efficacy and broader safety profile for fluid retention. Arch Pharm Res 2009;32:721-7
   PubMed Web of Science ®Google Scholar
• Ching HC, Lesley AM, Margaret SW, A novel selective peroxisome proliferator-activator receptor-gamma modulator—SPPAR-gammaM5 improves insulin sensitivity with diminished adverse cardiovascular effects. Eur J Pharmacol 2008;584:192-01
   PubMed Web of Science ®Google Scholar
• Acton JJ III, Akiyama TE, Chang CH, Discovery of (2R)-2-(3-{3-[(4-Methoxyphenyl) carbonyl]-2-methyl-6- (trifluoromethoxy)-1H- indol-1-}phenoxy) butanoic acid (MK-0533): a novel selective peroxisome proliferator-activated receptor gamma modulator for the treatment of type 2 diabetes mellitus with a reduced potential to increase plasma and extracellular fluid volume. J Med Chem 2009;52:3846-54
   PubMed Web of Science ®Google Scholar
• Dropinski JF, Akiyama T, Einstein M, Synthesis and biological activities of novel aryl indole-2-carboxylic acid analogs as PPAR-gamma partial agonists. Bioorg Med Chem Lett 2005;15:5035-8
   PubMed Web of Science ®Google Scholar
• Kim J, Han DC, Kim JM, PPAR- gamma partial agonist, KR-62776, inhibits adipocyte differentiation via activation of ERK. Cell Mol Life Sci 2009;66:1766-81
   PubMed Web of Science ®Google Scholar
• Higgins LS, Mantzoros CS. The development of INT131 as a selective PPAR-gamma modulator: approach to a safer insulin sensitizer. PPAR Res 2008;2008:1-9
   Google Scholar
• Reginato MJ, Bailey ST, Krakow SL, A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor gamma-activating properties. J Biol Chem 1998;273:32679-84
   PubMed Web of Science ®Google Scholar
• Misra P, Chakrabarti R, Vikramadithyan RK, PAT5A: a partial agonist of peroxisome proliferator-activated receptor gamma is a potent antidiabetic thiazolidinedione yet weakly adipogenic. J Pharmacol Exp Ther 2003;306:763-71
   PubMed Web of Science ®Google Scholar
• Miller A, Otto K, Hawkins E, A peroxisome proliferator-activated receptor a/g dual agonist with a unique in vitro profile and potent glucose and lipid effects in rodent models of type 2 diabetes and dyslipidemia. Mol Endocrinol 2005;19:1593-605
   PubMed Web of Science ®Google Scholar
• Shi G, Dropinski J, McKeever B, Design and synthesis of r-aryloxyphenylacetic acid derivatives: a novel class of PPAR-alpha/g dual agonists with potent antihyperglycemic and lipid modulating activity. J Med Chem 2005;48:4457-68
   PubMed Web of Science ®Google Scholar
• Gregoire F, Clarke H, Chen X, MBX-213, a novel dual PPAR-alpha/gamma agonist with beneficial effects on lipid profiles and insulin resistance [abstract 121]. 16th International Symposium on Drugs Affecting Lipid Metabolism, New York, 4 – 7 October 2007
   Google Scholar
• Artisa D, Lina J, Zhanga C, Scaffold-based discovery of indeglitazar, a PPAR- pan-active anti-diabetic agent. Proc Natl Acad Sci USA 2009;106:262-7
   PubMed Web of Science ®Google Scholar
• Colca JR, Kletzien RF. What has prevented the expansion of insulin sensitisers? Expert Opin Investig Drugs 2006;15:205-10
   PubMed Web of Science ®Google Scholar
• Tontonoz P, Hu E, Graves RA, mPPAR-gamma2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 1994;8:1224-34
   PubMed Web of Science ®Google Scholar
• Dey D, Medicherla S, Neogi P, A novel peroxisome proliferator-activated gamma (PPAR-gamma) agonist, CLX-0921, has potent antihyperglycemic activity with low adipogenic potential. Metabolism 2003;52:1012-18
   PubMed Web of Science ®Google Scholar
• Fujimura T, Kimura C, Oe T, A selective peroxisome proliferator-activated receptor gamma modulator with distinct fat cell regulation properties. J Pharmacol Exp Ther 2006;318:863-71
   PubMed Web of Science ®Google Scholar
• Lu IL, Huang CF, Peng YH, Structure-based drug design of a novel family of PPAR-gamma partial agonists: virtual screening, X-ray crystallography, and in vitro/in vivo biological activities. J Med Chem 2006;49:2703-12
   PubMed Web of Science ®Google Scholar
• Li Y, Wang Z, Furukawa N, T2384, a novel antidiabetic agent with unique peroxisome proliferator-activated receptor gamma binding properties. J Biol Chem 2008;283:9168-76
   PubMed Web of Science ®Google Scholar
• Adamson D, Frew D, Tatoud R, Diclofenac antagonizes peroxisome proliferator-activated receptor-gamma signaling. Mol Pharmacol 2002;61:7-12
   PubMed Web of Science ®Google Scholar
• Adams M, Montague CT, Prins JB, Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J Clin Invest 1997;100:3149-53
   PubMed Web of Science ®Google Scholar
• Wagner JA, Wright EC, Ennis MM, Utility of adiponectin as a biomarker predictive of glycemic efficacy is demonstrated by collaborative pooling of data from clinical trials conducted by multiple sponsors. Clin Pharmacol Ther 2009;86:619-25
   Google Scholar
• Acton JJ III, Black RM, Jones AB, Benzoyl 2-methyl indoles as selective PPAR-gamma modulators. Bioorg Med Chem Lett 2005;15:357-62
   PubMed Web of Science ®Google Scholar
• Larsen PJ, Lykkegaard K, Larsen LK, Dissociation of antihyperglycaemic and adverse effects of partial peroxisome proliferator-activated receptor (PPAR-gamma) agonist balaglitazone. Eur J Pharmacol 2008;596:173-9
   PubMed Web of Science ®Google Scholar
• Xie W, Nie Y, Du L, Preventive effects of fenofibrate on insulin resistance, hyperglycaemia, visceral fat accumulation in NIH mice induced by small-dose streptozotocin and lard. Pharmacol Res 2007;55:392-99
   PubMed Web of Science ®Google Scholar
• Clasen R, Schupp M, Foryst-Ludwig A, PPAR-gamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension 2005;46:137-43
   PubMed Web of Science ®Google Scholar
• Vikramadithyan RK, Chakrabarti R, Misra P, Euglycemic and hypolipidemic activity of PAT5A: a unique thiazolidinedione with weak peroxisome proliferator activated receptor gamma activity. Metabolism 2000;49:1417-23
   PubMed Web of Science ®Google Scholar
• Chandalia A, Clarke HJ, Clemens LE, MBX-102/JNJ39659100, a novel non-TZD selective partial PPAR-gamma agonist lowers triglyceride independently of PPAR-alpha activation. PPAR Res 2009;2009:1-12
   Google Scholar
• Sakamoto J, Kimura H, Moriyama S, Activation of human peroxisome proliferator-activated receptor (PPAR-) subtypes by pioglitazone. Biochem Biophys Res Commun 2000;278:704-11
   PubMed Web of Science ®Google Scholar
• Rizos CV, Elisaf MS, Mikhailidis DP, How safe is the use of thiazolidinediones in clinical practice?. Expert Opin Drug Saf 2009;8:15-32
   PubMed Web of Science ®Google Scholar
• Astellas annual report on investor relations, 2005. Available from: http://www.astellas.com/en/ir/library/pdf/annual2005_eg.pdf [Last accessed 8 October 2009]
   Google Scholar
• Efficacy and tolerability of MK0533 in patients with type 2 diabetes. Available from: http://clinicaltrial.gov/ct2/show/ NCT00543959 [Last accessed 8 October 2009]
   Google Scholar
• Julio R, Fernando F, Sherwyn S, 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 [abstract 44-OR]. 65th Scientific Sessions Am Diabetes Assoc (ADA), 10 – 14 June, San Diego; 2005
   Google Scholar
• Safety and tolerability study of MBX-2044 in patients with type 2 diabetes. Available from: http://www.metabolex.com/MBX-2044.html [Last accessed 8 October 2009]
   Google Scholar
• Dunn F, Higgins L, Depaoli A. INT131: a selective PPAR-gamma modulator (SPPAR-M) for type 2 diabetes mellitus (T2DM). Diabetes 2008:57(Suppl 1): abstract 499-P
   Google Scholar
• Impact of INT131 besylate, a selective PPAR-gamma modulator (SPPAR-M), on glycemic control in patients with type 2 diabetes in a 24-week Phase 2b study (INT131-007), 30 September 2009. Available from: http://www.intekrin.com/news-n-media-press-releases-expanded.html [Last accessed 8 October 2009]
   Google Scholar
• Koev D, Ionescu-Trgoviste C, Rosenthal A, Balaglitazone, a new thiazolidinedione, improves glucose and lipid control in patients with type 2 diabetes. Diabetes 2003;52(Suppl 1):530-P
   Google Scholar
• Katz A, Weisel K, Hickey L, Safety and preliminary efficacy of PPM-204, a novel pan-PPAR- agonist, in treatment-naive type 2 diabetic subjects. 43rd Annu Meet Eur Assoc Study Diabetes (EASD), [abstract 0220 OP 37], 17 – 21 September, Amsterdam; 2007
   Google Scholar
• Nesto RW, Bell D, Bonow RO, Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 2003;108:2941-48
   PubMed Web of Science ®Google Scholar
• Boden G, Zang M. Recent findings concerning thiazolidinediones in the treatment of diabetes. Expert Opin Invest Drugs 2006;15:243-50
   PubMed Web of Science ®Google Scholar
• Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care 2007;30:2148-53
   PubMed Web of Science ®Google Scholar
• Song J, Knepper MA, Hu X, Rosiglitazone activates renal sodium- and water reabsorptive pathways and lowers blood pressure in normal rats. J Pharmacol Exp Ther 2004;308:426-33
   PubMed Web of Science ®Google Scholar
• Yang T, Soodvilai S. Renal and vascular mechanisms of thiazolidinedione-induced fluid retention. PPAR Res 2008;2008:1-8
   Google Scholar
• Berlie HD, Kalus JS, Jaber LA. Thiazolidinediones and the risk of edema: a meta-analysis. Diabetes Res Clin Pract 2007;76:279-89
   PubMed Web of Science ®Google Scholar
• Minoura H, Takeshita S, Ita M, Pharmacological characteristics of a novel nonthiazolidinedione insulin sensitizer, FK614. Eur J Pharmacol 2004;494:273-81
   PubMed Web of Science ®Google Scholar
• DePaoli A, Higgins LS. INT131, a non-TZD selective PPAR-gamma modulator (SPPAR-M) does not cause toxicities typical of TZD full PPAR-gamma agonists following 6-month high dose treatment of rats or monkeys [abstract 922]. 44th Annu Meet European Association for the Study of Diabetes, Rome, Italy, March 09
   Google Scholar
• Pickavance LC, Tadayyon M, Widdowson PS, Therapeutic index for rosiglitazone in dietary obese rats: separation of efficacy and haemodilution. Br J Pharmacol 1999;128:1570-6
   PubMed Web of Science ®Google Scholar
• Guidance for industry diabetes mellitus–evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Clinical/Medical, 1 – 5 December 2008
   Google Scholar
• Kelly IE, Han TS, Walsh K, Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care 1999;22:288-93
   PubMed Web of Science ®Google Scholar
• Bogacka I, Xie H, Bray GA, The effect of pioglitazone on peroxisome proliferator-activated receptor-gamma target genes related to lipid storage in vivo. Diabetes Care 2004;27:1660-7
   PubMed Web of Science ®Google Scholar
• Shimaya A, Kurosaki E, Nakano R, The novel hypoglycemic agent YM440 normalizes hyperglycemia without changing body fat weight in diabetic db/db mice. Metabolism 2000;49:411-7
   PubMed Web of Science ®Google Scholar
• Zanchi A, Dulloo AG, Perregaux C, Telmisartan prevents the glitazone-induced weight gain without interfering with its insulin-sensitizing properties. Am J Physiol Endocrinol Metab 2007;293:E91-5
   PubMed Web of Science ®Google Scholar
• Chou CJ, Haluzik M, Gregory C, WY14, 643, a peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice. J Biol Chem 2002:277;24484-89
   PubMed Web of Science ®Google Scholar
• Pickavance L, Widdowson PS, King P, The development of overt diabetes in young Zucker diabetic fatty (ZDF) rats and the effects of chronic MCC-555 treatment. Br J Pharmacol 1998;125:767-70
   PubMed Web of Science ®Google Scholar
• Mueller E, Sarraf P, Tontonoz P, Terminal differentiation of human breast cancer through PPAR- gamma. Mol Cell 1998;1:465-70
   PubMed Web of Science ®Google Scholar
• Lefebvre A, Chen I, Desreumaux P, Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin /+ mice. Nat Med 1998;4:1053-7
   PubMed Web of Science ®Google Scholar
• Saez E, Tontonoz P, Nelson MC, Activators of the nuclear receptor PPAR-gamma enhances colon polyp formation. Nat Med 1998;4:1058-61
   PubMed Web of Science ®Google Scholar
• Saez E, Rosenfeld J, Livolsi A, PPAR-gamma signaling exacerbates mammary gland tumor development. Genes Dev 2004;18:528-40
   PubMed Web of Science ®Google Scholar
• MacLean CD, Littenberg B, Gagnon M, The Vermont Diabetes Information System (VDIS): study design and subject recruitment for a cluster randomized trial of a decision support system in a regional sample of primary care practices. Clin Trials 2004;1:532-44
   PubMedGoogle Scholar
• Goldstein M. PROactive study. Lancet 2006;367:23-6
   PubMedGoogle Scholar
• Monami M, Lamanna C, Marchionni N, Rosiglitazone and risk of cancer: a meta-analysis of randomized clinical trials. Diabetes Care 2008;31:1455-60
   PubMed Web of Science ®Google Scholar
• Wart V. Transforming the treatment of metabolic disease. Bay Bio Meeting, South San Francisco, CA, USA, 16 April 2009. Available from: http://www.baybio.org/pdf/AC09_Track4_945.pdf [Last accessed 8 October 2009]
   Google Scholar
• Metabolic Disease Type 2 Diabetic program, November 2008. Available from: www.plexxikon.com/Plexxikon_Diabetes_111708.pdf [Last accessed 8 October 2009]
   Google Scholar
• Chronic Cardiovascular Safety of INT131 Besylate, a Selective PPAR-gamma Modulator (SPPAR-M) in Rodents and Monkeys is Differentiated from TZD Full Agonists, 30 September 2009. Available from: http://www.intekrin.com/news-n-media-press-releases-expanded.html [Last accessed 8 October 2009]
   Google Scholar
• Lecka-Czernik B, Gubrij I, Moerman EJ, Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR-gamma2. J Cell Biochem 1999;74:357-71
   PubMed Web of Science ®Google Scholar
• Sottile V, Seuwen K, Kneissel M. Enhanced marrow adipogenesis and bone resorption in estrogen deprived rats treated with the PPAR-gamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 2004;75:329-37
   PubMed Web of Science ®Google Scholar
• Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009;180:32-9
   PubMed Web of Science ®Google Scholar
• Henriksen K, Byrjalsen I, Nielsen RH, A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats. Eur J Pharmacol 2009;616:340-5
   PubMed Web of Science ®Google Scholar
• Lazarenko OP, Rzonca SO, Suva LJ, Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat. Bone 2006;38:74-84
   PubMed Web of Science ®Google Scholar
• Koppen A, Houtman R, Pijnenburg D, Nuclear receptor-coregulator interaction profiling identifies TRIP3 as a novel PPAR-gamma cofactor. Mol Cell Proteomics 2009;8:2212-26
   PubMed Web of Science ®Google Scholar
• Biserni A, Giannessi F, Sciarroni AF, In vivo imaging reveals selective peroxisome proliferator activated receptor modulator activity of the synthetic ligand 3-(1-(4-chlorobenzyl)-3- t-butylthio-5-isopropylindol-2-yl)- 2,2-dimethylpropanoic acid (MK-886). Mol Pharmacol 2008;73:1434-43
   PubMed Web of Science ®Google Scholar
• Deuz H, Lefebvre B, Poulain P, Regulation of human ApoA-I by Gemfibrozil and fenofibrate through selective PPAR-gamma modulation. Arterioscler Thromb Vasc Biol 2005;25:585-91
   PubMed Web of Science ®Google Scholar
• Genfit: GFT505 Phase IIa study is progressing rapidly, July 2009. Available from: http://www.genfit.com/fileadmin/press/press/press_release/PR_GFT505_2009-07-07.pdf [Last accessed 8 October 2009]
   Google Scholar
• Shearer BG, Patel HS, Billin AN, Discovery of a novel class of PPAR-d partial agonists. Bioorg Med Chem Lett 2008;18:5018-22
   PubMed Web of Science ®Google Scholar
• Liu KG, Lambert MH, Leesnitzer LM, Identification of a series of PPAR-gamma/δ dual agonists via solid-phase parallel synthesis. Bioorg Med Chem Lett 2001;11:2959-62
   PubMed Web of Science ®Google Scholar
• Heidi S, Ou Li, Scott C, Differential activation of peroxisome proliferator-activated receptor gamma by troglitazone and rosiglitazone. Diabetes 2000;49:539-47
   PubMed Web of Science ®Google Scholar
• Imoto H, Imamiya E, Momose Y, Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives. Chem Pharm Bull 2002;50:1349-57
   PubMed Web of Science ®Google Scholar
• Thor M, Beierlein K, Dykes G, Synthesis and pharmacological evaluation of a new class of peroxisome proliferator-activated receptor modulators. Bioorg Med Chem Lett 2002;12:3565-7
   PubMed Web of Science ®Google Scholar
• Kurosaki E, Nakano R, Shimaya A, Differential effects of YM440 a hypoglycemic agent on binding to a peroxisome proliferator-activated receptor gamma and its transactivation. Biochem Pharmacol 2003;65:795-805
   PubMed Web of Science ®Google Scholar
• Ostberg T, Svensson S, Sele G, A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects. J Biol Chem 2004;279:41124-30
   PubMed Web of Science ®Google Scholar
• Liu K, Black RM, Acton JJ III, Synthesis of PPAR-gamma modulator with improved pharmacological profiles. Bioorg Med Chem Lett 2005;15:2437-40
   PubMed Web of Science ®Google Scholar
• Schupp M, Lee L, Frost N, Regulation of peroxisome proliferator-activated receptor gamma activity by losartan metabolites. Hypertension 2006;47:586-9
   PubMed Web of Science ®Google Scholar
• DRL 17564, a selective PPAR-gamma modulator: potential in type 2 diabetes [abstract 897-P]. 67th Annu Meet Sci Sess Am Diabetes Assoc (ADA), 22 – 26 June, Chicago; 2007
   Google Scholar
• Minoura H, Takeshita S, Kimura C, Mechanism by which a novel non-thiazolidinedione peroxisome proliferator-activated receptor gamma agonist, FK614, ameliorates insulin resistance in Zucker fatty rats. Diabetes Obes Metab 2007;9:369-78
   PubMed Web of Science ®Google Scholar
• Safety and efficacy study of metaglidasen in type 2 diabetes in patients sub-optimally controlled on insulin. Available from: http://clinicaltrial.gov/ct2/show/ NCT00353587 [Last accessed 8 October 2009]
   Google Scholar
• Efficacy and safety of treatment with balaglitazone in type 2 diabetes patients on stable insulin therapy (BALLET). Available from: http://clinicaltrial.gov/ct2/show/ NCT00515632 [Last accessed 8 October 2009]
   Google Scholar