{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:56:20Z","timestamp":1790070980554,"version":"4.0.1"},"reference-count":56,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2008,12]]},"DOI":"10.1124\/jpet.108.143271","type":"journal-article","created":{"date-parts":[[2008,9,18]],"date-time":"2008-09-18T00:44:37Z","timestamp":1221698677000},"page":"716-726","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel Peroxisome Proliferator-Activated Receptor \u03b1 Agonists Lower Low-Density Lipoprotein and Triglycerides, Raise High-Density Lipoprotein, and Synergistically Increase Cholesterol Excretion with a Liver X Receptor Agonist"],"prefix":"10.1016","volume":"327","author":[{"given":"Ranjan","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth T.","family":"Locke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowman","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Meyers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossain","family":"Monshizadegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Search","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Grimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"O\u2019Malley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Blanar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Tino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rai Ajit","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.108.143271_bib1","doi-asserted-by":"crossref","unstructured":"Beyer TP, Schmidt RJ, Foxworthy P, Zhang Y, Dai J, Bensch WR, Kauffman RF, Gao H, Ryan TP, Jiang XC, et al. (2004) Coadministration of a liver x receptor agonist and a peroxisome proliferator activator receptor-alpha agonist in mice: effects of nuclear receptor interplay on high-density lipoprotein and triglyceride metabolism in vivo. J Pharmacol Exp Ther 309: 861-868.","DOI":"10.1124\/jpet.103.064535"},{"key":"10.1124\/jpet.108.143271_bib2","doi-asserted-by":"crossref","unstructured":"Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, and Skene AM (2004) Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350: 1495-1504.","DOI":"10.1056\/NEJMoa040583"},{"key":"10.1124\/jpet.108.143271_bib3","doi-asserted-by":"crossref","unstructured":"Cheung C, Akiyama TE, Ward JM, Nicol CJ, Feigenbaum L, Vinson C, and Gonzalez FJ (2004) Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res 64: 3849-3854.","DOI":"10.1158\/0008-5472.CAN-04-0322"},{"key":"10.1124\/jpet.108.143271_bib4","doi-asserted-by":"crossref","unstructured":"Cohen JC, Boerwinkle E, Mosley TH Jr, and Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354: 1264-1272.","DOI":"10.1056\/NEJMoa054013"},{"key":"10.1124\/jpet.108.143271_bib5","doi-asserted-by":"crossref","unstructured":"DAIS Investigators (2001) Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 357: 905-910.","DOI":"10.1016\/S0140-6736(00)04209-4"},{"key":"10.1124\/jpet.108.143271_bib6","doi-asserted-by":"crossref","unstructured":"Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, and Wahli W (1992) Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68: 879-887.","DOI":"10.1016\/0092-8674(92)90031-7"},{"key":"10.1124\/jpet.108.143271_bib7","doi-asserted-by":"crossref","unstructured":"Duez H, Chao YS, Hernandez M, Torpier G, Poulain P, Mundt S, Mallat Z, Teissier E, Burton CA, Tedgui A, et al. (2002) Reduction of atherosclerosis by the peroxisome proliferator-activated receptor alpha agonist fenofibrate in mice. J Biol Chem 277: 48051-48057.","DOI":"10.1074\/jbc.M206966200"},{"key":"10.1124\/jpet.108.143271_bib8","unstructured":"El-Hage J (2005) PPAR agonists: nonclinical and clinical toxicity and safety assessments, in Lorenzizni Foundation Third International Symposium on PPARs Efficacy and Safety; Monte Carlo, Monaco."},{"key":"10.1124\/jpet.108.143271_bib9","doi-asserted-by":"crossref","unstructured":"Forman BM, Chen J, and Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A 94: 4312-4317.","DOI":"10.1073\/pnas.94.9.4312"},{"key":"10.1124\/jpet.108.143271_bib10","doi-asserted-by":"crossref","unstructured":"Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, et al. (1987) Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 317: 1237-1245.","DOI":"10.1056\/NEJM198711123172001"},{"key":"10.1124\/jpet.108.143271_bib11","doi-asserted-by":"crossref","unstructured":"Genest JJ, McNamara JR, Salem DN, and Schaefer EJ (1991) Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol 67: 1185-1189.","DOI":"10.1016\/0002-9149(91)90924-A"},{"key":"10.1124\/jpet.108.143271_bib12","doi-asserted-by":"crossref","unstructured":"Goldbourt U, Yaari S, and Medalie JH (1997) Isolated low HDL cholesterol as a risk factor for coronary heart disease mortality: a 21-year follow-up of 8000 men. Arterioscler Thromb Vasc Biol 17: 107-113.","DOI":"10.1161\/01.ATV.17.1.107"},{"key":"10.1124\/jpet.108.143271_bib13","doi-asserted-by":"crossref","unstructured":"Gordon DJ, Knoke J, Probstfield JL, Superko R, and Tyroler HA (1986) High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial. Circulation 74: 1217-1225.","DOI":"10.1161\/01.CIR.74.6.1217"},{"key":"10.1124\/jpet.108.143271_bib14","doi-asserted-by":"crossref","unstructured":"Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, and Tyroler HA (1989) High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79: 8-15.","DOI":"10.1161\/01.CIR.79.1.8"},{"key":"10.1124\/jpet.108.143271_bib15","doi-asserted-by":"crossref","unstructured":"Hopkins PN, Heiss G, Ellison RC, Province MA, Pankow JS, Eckfeldt JH, and Hunt SC (2003) Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. Circulation 108: 519-523.","DOI":"10.1161\/01.CIR.0000081777.17879.85"},{"key":"10.1124\/jpet.108.143271_bib16","doi-asserted-by":"crossref","unstructured":"Hostetler HA, Petrescu AD, Kier AB, and Schroeder F (2005) Peroxisome proliferator-activated receptor alpha interacts with high affinity and is conformationally responsive to endogenous ligands. J Biol Chem 280: 18667-18682.","DOI":"10.1074\/jbc.M412062200"},{"key":"10.1124\/jpet.108.143271_bib17","doi-asserted-by":"crossref","unstructured":"Issemann I and Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347: 645-650.","DOI":"10.1038\/347645a0"},{"key":"10.1124\/jpet.108.143271_bib18","doi-asserted-by":"crossref","unstructured":"Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, et al. (2005) Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366: 1849-1861.","DOI":"10.1016\/S0140-6736(05)67667-2"},{"key":"10.1124\/jpet.108.143271_bib19","doi-asserted-by":"crossref","unstructured":"Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K, and Evans RM (1994) Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 91: 7355-7359.","DOI":"10.1073\/pnas.91.15.7355"},{"key":"10.1124\/jpet.108.143271_bib20","doi-asserted-by":"crossref","unstructured":"Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, et al. (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 94: 4318-4323.","DOI":"10.1073\/pnas.94.9.4318"},{"key":"10.1124\/jpet.108.143271_bib21","doi-asserted-by":"crossref","unstructured":"Laffitte BA, Joseph SB, Chen M, Castrillo A, Repa J, Wilpitz D, Mangelsdorf D, and Tontonoz P (2003) The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions. Mol Cell Biol 23: 2182-2191.","DOI":"10.1128\/MCB.23.6.2182-2191.2003"},{"key":"10.1124\/jpet.108.143271_bib22","doi-asserted-by":"crossref","unstructured":"LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, et al. (2005) Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352: 1425-1435.","DOI":"10.1056\/NEJMoa050461"},{"key":"10.1124\/jpet.108.143271_bib23","unstructured":"Li J, Kennedy LJ, Shi Y, Tao S, Ye X-Y, Chen SY, Raju R, Wang Y, Hernandez A, Zhang H, et al. (2007) Discovery of a novel, potent PPARalpha selective activator BMS-687453 in Abstracts of Papers, 234th ACS National Meeting; Boston, MA."},{"key":"10.1124\/jpet.108.143271_bib24","doi-asserted-by":"crossref","unstructured":"Linsel-Nitschke P and Tall AR (2005) HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat Rev Drug Discov 4: 193-205.","DOI":"10.1038\/nrd1658"},{"key":"10.1124\/jpet.108.143271_bib25","doi-asserted-by":"crossref","unstructured":"Liu PC, Huber R, Stow MD, Schlingmann KL, Collier P, Liao B, Link J, Burn TC, Hollis G, Young PR, et al. (2003) Induction of endogenous genes by peroxisome proliferator activated receptor alpha ligands in a human kidney cell line and in vivo. J Steroid Biochem Mol Biol 85: 71-79.","DOI":"10.1016\/S0960-0760(03)00135-3"},{"key":"10.1124\/jpet.108.143271_bib26","doi-asserted-by":"crossref","unstructured":"Miao B, Zondlo S, Gibbs S, Cromley D, Hosagrahara VP, Kirchgessner TG, Billheimer J, and Mukherjee R (2004) Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J Lipid Res 45: 1410-1417.","DOI":"10.1194\/jlr.M300450-JLR200"},{"key":"10.1124\/jpet.108.143271_bib27","doi-asserted-by":"crossref","unstructured":"Mukherjee R (2002) PPARs: Versatile Targets for Future Therapy for Obesity, Diabetes and Cardiovascular Diseases. Drug News Perspect 15: 261-267.","DOI":"10.1358\/dnp.2002.15.5.840038"},{"key":"10.1124\/jpet.108.143271_bib28","doi-asserted-by":"crossref","unstructured":"Mukherjee R, Jow L, Croston GE and Paterniti JR Jr (1997) Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgammal and activation with retinoid X receptor agonists and antagonists. J Biol Chem 272: 8071-8076.","DOI":"10.1074\/jbc.272.12.8071"},{"key":"10.1124\/jpet.108.143271_bib29","doi-asserted-by":"crossref","unstructured":"Mukherjee R, Jow L, Noonan D, and McDonnell DP (1994) Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators. J Steroid Biochem Mol Biol 51: 157-166.","DOI":"10.1016\/0960-0760(94)90089-2"},{"key":"10.1124\/jpet.108.143271_bib30","doi-asserted-by":"crossref","unstructured":"Mukherjee R, Sun S, Santomenna L, Miao B, Walton H, Liao B, Locke K, Zhang JH, Nguyen SH, Zhang LT, et al. (2002) Ligand and coactivator recruitment preferences of peroxisome proliferator activated receptor alpha. J Steroid Biochem Mol Biol 81: 217-225.","DOI":"10.1016\/S0960-0760(02)00066-3"},{"key":"10.1124\/jpet.108.143271_bib31","doi-asserted-by":"crossref","unstructured":"Naik SU, Wang X, Da Silva JS, Jaye M, Macphee CH, Reilly MP, Billheimer JT, Rothblat GH, and Rader DJ (2006) Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation 113: 90-97.","DOI":"10.1161\/CIRCULATIONAHA.105.560177"},{"key":"10.1124\/jpet.108.143271_bib32","doi-asserted-by":"crossref","unstructured":"Nissen SE, Nicholls SJ, Wolski K, Howey DC, McErlean E, Wang MD, Gomez EV, and Russo JM (2007) Effects of a potent and selective PPAR-alpha agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA 297: 1362-1373.","DOI":"10.1001\/jama.297.12.1362"},{"key":"10.1124\/jpet.108.143271_bib33","doi-asserted-by":"crossref","unstructured":"Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, et al. (2001) A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A 98: 5306-5311.","DOI":"10.1073\/pnas.091021198"},{"key":"10.1124\/jpet.108.143271_bib34","doi-asserted-by":"crossref","unstructured":"Osumi T, Wen JK, and Hashimoto T (1991) Two cis-acting regulatory sequences in the peroxisome proliferator-responsive enhancer region of rat acyl-CoA oxidase gene. Biochem Biophys Res Commun 175: 866-871.","DOI":"10.1016\/0006-291X(91)91645-S"},{"key":"10.1124\/jpet.108.143271_bib35","doi-asserted-by":"crossref","unstructured":"Post SM, Duez H, Gervois PP, Staels B, Kuipers F, and Princen HM (2001) Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression. Arterioscler Thromb Vasc Biol 21: 1840-1845.","DOI":"10.1161\/hq1101.098228"},{"key":"10.1124\/jpet.108.143271_bib36","doi-asserted-by":"crossref","unstructured":"Reddy JK, Goel SK, Nemali MR, Carrino JJ, Laffler TG, Reddy MK, Sperbeck SJ, Osumi T, Hashimoto T, and Lalwani ND (1986) Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase\/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc Natl Acad Sci U S A 83: 1747-1751.","DOI":"10.1073\/pnas.83.6.1747"},{"key":"10.1124\/jpet.108.143271_bib37","doi-asserted-by":"crossref","unstructured":"Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, and Mangelsdorf DJ (2000a) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14: 2819-2830.","DOI":"10.1101\/gad.844900"},{"key":"10.1124\/jpet.108.143271_bib38","doi-asserted-by":"crossref","unstructured":"Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, Heyman RA, Dietschy JM, and Mangelsdorf DJ (2000b) Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289: 1524-1529.","DOI":"10.1126\/science.289.5484.1524"},{"key":"10.1124\/jpet.108.143271_bib39","doi-asserted-by":"crossref","unstructured":"Rubin EM, Ishida BY, Clift SM, and Krauss RM (1991) Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses. Proc Natl Acad Sci U S A 88: 434-438.","DOI":"10.1073\/pnas.88.2.434"},{"key":"10.1124\/jpet.108.143271_bib40","doi-asserted-by":"crossref","unstructured":"Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, et al. (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 341: 410-418.","DOI":"10.1056\/NEJM199908053410604"},{"key":"10.1124\/jpet.108.143271_bib41","doi-asserted-by":"crossref","unstructured":"Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, and Auwerx J (1996) PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 15: 5336-5348.","DOI":"10.1002\/j.1460-2075.1996.tb00918.x"},{"key":"10.1124\/jpet.108.143271_bib42","doi-asserted-by":"crossref","unstructured":"Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S, Wang S, Thoolen M, Mangelsdorf DJ, et al. (2000) Role of LXRs in control of lipogenesis. Genes Dev 14: 2831-2838.","DOI":"10.1101\/gad.850400"},{"key":"10.1124\/jpet.108.143271_bib43","doi-asserted-by":"crossref","unstructured":"Seethala R, Golla R, Ma Z, Zhang H, O\u2019Malley K, Lippy J, Cheng L, Mookhtiar K, Farrelly D, Zhang L, et al. (2007) A rapid, homogeneous, fluorescence polarization binding assay for peroxisome proliferator-activated receptors alpha and gamma using a fluorescein-tagged dual PPARalpha\/gamma activator. Anal Biochem 363: 263-274.","DOI":"10.1016\/j.ab.2007.01.022"},{"key":"10.1124\/jpet.108.143271_bib44","doi-asserted-by":"crossref","unstructured":"Semple RK, Meirhaeghe A, Vidal-Puig AJ, Schwabe JW, Wiggins D, Gibbons GF, Gurnell M, Chatterjee VK, and O\u2019Rahilly S (2005) A dominant negative human peroxisome proliferator-activated receptor (PPAR){alpha} is a constitutive transcriptional corepressor and inhibits signaling through all PPAR isoforms. Endocrinology 146: 1871-1882.","DOI":"10.1210\/en.2004-1405"},{"key":"10.1124\/jpet.108.143271_bib45","doi-asserted-by":"crossref","unstructured":"Sher T, Yi HF, McBride OW, and Gonzalez FJ (1993) cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 32: 5598-5604.","DOI":"10.1021\/bi00072a015"},{"key":"10.1124\/jpet.108.143271_bib46","unstructured":"Shi Y, Li J, Kennedy LJ, Tao H, Ye X-Y, Chen S, Zhang H, Hernandez A, Chen S, Lai Z, et al. (2007) Discovery and structure-activity relationships of BMS-711939, a potent and highly selective PPARalpha activator, in Abstracts of Papers, 234th ACS National Meeting, Boston, MA."},{"key":"10.1124\/jpet.108.143271_bib47","doi-asserted-by":"crossref","unstructured":"Sugden MC, Bulmer K, Augustine D, and Holness MJ (2001) Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion. Diabetes 50: 2729-2736.","DOI":"10.2337\/diabetes.50.12.2729"},{"key":"10.1124\/jpet.108.143271_bib48","doi-asserted-by":"crossref","unstructured":"The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group (1998) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 339: 1349-1357.","DOI":"10.1056\/NEJM199811053391902"},{"key":"10.1124\/jpet.108.143271_bib49","doi-asserted-by":"crossref","unstructured":"The Scandinavian Simvastatin Survival Study (4S) Group (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344: 1383-1389.","DOI":"10.1016\/S0140-6736(94)90566-5"},{"key":"10.1124\/jpet.108.143271_bib50","doi-asserted-by":"crossref","unstructured":"Tontonoz P, Hu E, and Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79: 1147-1156 [Erratum in: Cell 1995 Mar 24;80(6):following 957].","DOI":"10.1016\/0092-8674(94)90006-X"},{"key":"10.1124\/jpet.108.143271_bib51","doi-asserted-by":"crossref","unstructured":"Valasek MA, Clarke SL, and Repa JJ (2007) Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPC1L1 expression in mouse. J Lipid Res 48: 2725-2735.","DOI":"10.1194\/jlr.M700345-JLR200"},{"key":"10.1124\/jpet.108.143271_bib52","doi-asserted-by":"crossref","unstructured":"Vu-Dac N, Chopin-Delannoy S, Gervois P, Bonnelye E, Martin G, Fruchart JC, Laudet V, and Staels B (1998) The nuclear receptors peroxisome proliferator-activated receptor alpha and Rev-erbalpha mediate the species-specific regulation of apolipoprotein A-I expression by fibrates. J Biol Chem 273: 25713-25720.","DOI":"10.1074\/jbc.273.40.25713"},{"key":"10.1124\/jpet.108.143271_bib53","doi-asserted-by":"crossref","unstructured":"Wang PR, Guo Q, Ippolito M, Wu M, Milot D, Ventre J, Doebber T, Wright SD, and Chao YS (2001) High fat fed hamster, a unique animal model for treatment of diabetic dyslipidemia with peroxisome proliferator activated receptor alpha selective agonists. Eur J Pharmacol 427: 285-293.","DOI":"10.1016\/S0014-2999(01)01249-3"},{"key":"10.1124\/jpet.108.143271_bib54","doi-asserted-by":"crossref","unstructured":"Willson TM, Brown PJ, Sternbach DD, and Henke BR (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem 43: 527-550.","DOI":"10.1021\/jm990554g"},{"key":"10.1124\/jpet.108.143271_bib55","doi-asserted-by":"crossref","unstructured":"Xu Y, Mayhugh D, Saeed A, Wang X, Thompson RC, Dominianni SJ, Kauffman RF, Singh J, Bean JS, Bensch WR, et al. (2003) Design and synthesis of a potent and selective triazolone-based peroxisome proliferator-activated receptor alpha agonist. J Med Chem 46: 5121-5124.","DOI":"10.1021\/jm034173l"},{"key":"10.1124\/jpet.108.143271_bib56","doi-asserted-by":"crossref","unstructured":"Yang Q, Nagano T, Shah Y, Cheung C, Ito S, and Gonzalez FJ (2008) The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha. Toxicol Sci 101: 132-139.","DOI":"10.1093\/toxsci\/kfm206"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652434697X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652434697X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.108.143271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T22:47:31Z","timestamp":1740005251000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002235652434697X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["S002235652434697X"],"URL":"https:\/\/doi.org\/10.1124\/jpet.108.143271","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2008,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel Peroxisome Proliferator-Activated Receptor \u03b1 Agonists Lower Low-Density Lipoprotein and Triglycerides, Raise High-Density Lipoprotein, and Synergistically Increase Cholesterol Excretion with a Liver X Receptor Agonist","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.108.143271","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2008 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}