Peroxisome proliferator-activated receptor agonists and antagonists: a patent review (2014-present)

References

• Makishima M. Nuclear receptors as targets for drug development: regulation of cholesterol and bile acid metabolism by nuclear receptors. J Pharmacol Sci. 2005;97:177–183.
   PubMed Web of Science ®Google Scholar
• Dubois V, Eeckhoute J, Lefebvre P, et al. Distinct but complementary contributions of PPAR isotypes to energy homeostasis. J Clin Invest. 2017;127:1202–1214.
   PubMed Web of Science ®Google Scholar
• Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347:645–650.
   PubMed Web of Science ®Google Scholar
• Dreyer C, Krey G, Keller H, et al. Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992;68:879–887.
   PubMed Web of Science ®Google Scholar
• Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 1994;91:7355–7359.
   PubMed Web of Science ®Google Scholar
• Takada I, Yu RT, Xu HE, et al. Alteration of a single amino acid in peroxisome proliferator-activated receptor-α (PPARα) generates a PPARδ phenotype. Mol Endocrinol. 2000;14:733–740.
   PubMedGoogle Scholar
• Tontonoz P, Hu E, Graves RA, et al. mPPARγ2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994;8:1224–1234.
   PubMed Web of Science ®Google Scholar
• Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995;83:841–850.
   PubMed Web of Science ®Google Scholar
• Rosenfeld MG, Lunyak VV, Glass CK. Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes Dev. 2006;20:1405–1428.
   PubMed Web of Science ®Google Scholar
• Brunmeir R, Xu F.Functional regulation of PPARs through post-translational modifications.Int J Mol Sci.2018;19.
   PubMed Web of Science ®Google Scholar
• Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem. 2008;77:289–312.
   PubMed Web of Science ®Google Scholar
• Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3:397–403.
   PubMed Web of Science ®Google Scholar
• Grygiel-Gorniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review. Nutr J. 2014;13:17.
   PubMed Web of Science ®Google Scholar
• Chakravarthy MV, Lodhi IJ, Yin L, et al. Identification of a physiologically relevant endogenous ligand for PPARα in liver. Cell. 2009;138:476–488.
   PubMed Web of Science ®Google Scholar
• Willson TM, Brown PJ, Sternbach DD, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527–550.
   PubMed Web of Science ®Google Scholar
• Berger J, Leibowitz MD, Doebber TW, et al. Novel peroxisome proliferator-activated receptor (PPAR) γ and PPARδ ligands produce distinct biological effects. J Biol Chem. 1999;274:6718–6725.
   PubMed Web of Science ®Google Scholar
• Sznaidman ML, Haffner CD, Maloney PR, et al. Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ) – synthesis and biological activity. Bioorg Med Chem Lett. 2003;13:1517–1521.
   PubMed Web of Science ®Google Scholar
• Oliver WR Jr., Shenk JL, Snaith MR, et al. A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A. 2001;98:5306–5311.
   PubMed Web of Science ®Google Scholar
• Kliewer SA, Lenhard JM, Willson TM, et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell. 1995;83:813–819.
   PubMed Web of Science ®Google Scholar
• Nagy L, Tontonoz P, Alvarez JGA, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. Cell. 1998;93:229–240.
   PubMed Web of Science ®Google Scholar
• Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J Biol Chem. 1995;270:12953–12956.
   PubMed Web of Science ®Google Scholar
• Takada I, Makishima M. PPARγ ligands and their therapeutic applications: a patent review (2008 – 2014). Expert Opin Ther Pat. 2015;25:175–191.
   PubMed Web of Science ®Google Scholar
• Choi JH, Banks AS, Estall JL, et al. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARγ by Cdk5. Nature. 2010;466:451–456.
   PubMed Web of Science ®Google Scholar
• Yasmin S, Jayaprakash V. Thiazolidinediones and PPAR orchestra as antidiabetic agents: from past to present. Eur J Med Chem. 2017;126:879–893.
   PubMed Web of Science ®Google Scholar
• Maltarollo VG, Kronenberger T, Windshugel B, et al. Advances and challenges in drug design of PPARδ ligands. Curr Drug Targets. 2018;19:144–154.
   PubMed Web of Science ®Google Scholar
• Lamers C, Schubert-Zsilavecz M, Merk D. Therapeutic modulators of peroxisome proliferator-activated receptors (PPAR): a patent review (2008-present). Expert Opin Ther Pat. 2012;22:803–841.
   PubMed Web of Science ®Google Scholar
• Marukome Co., Ltd. PPAR-alpha activator, pharmaceutical composition, food and drink, food additive, supplement and method of manufacturing the same. US20180015062A1. 2018. (applications).
   Google Scholar
• Yoshizaki Y, Kawasaki C, Cheng KC, et al. Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice. PeerJ. 2014;2:e540.
   PubMed Web of Science ®Google Scholar
• Takahashi H, Chi HY, Mohri S, et al. Rice koji extract enhances lipid metabolism through proliferator-activated receptor alpha (PPARα) activation in mouse liver. J Agric Food Chem. 2016;64:8848–8856.
   PubMed Web of Science ®Google Scholar
• Rush University Medical Center. Brain derived PPARa ligands. US20190060269A1. 2019. (applications).
   Google Scholar
• Roy A, Kundu M, Jana M, et al. Identification and characterization of PPARα ligands in the hippocampus. Nat Chem Biol. 2016;12:1075–1083.
   PubMed Web of Science ®Google Scholar
• Roy A, Jana M, Corbett GT, et al. Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator-activated receptor α. Cell Rep. 2013;4:724–737.
   PubMed Web of Science ®Google Scholar
• City of Hope. Peroxisome proliferator-activated receptor agonists. US20190077774A1. 2019. (applications).
   Google Scholar
• Yasutake K, Kohjima M, Kotoh K, et al. Dietary habits and behaviors associated with nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:1756–1767.
   PubMed Web of Science ®Google Scholar
• Ip E, Farrell GC, Robertson G, et al. Central role of PPARα-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology. 2003;38:123–132.
   PubMed Web of Science ®Google Scholar
• Barish GD, Narkar VA, Evans RM. PPARδ: a dagger in the heart of the metabolic syndrome. J Clin Invest. 2006;116:590–597.
   PubMed Web of Science ®Google Scholar
• Tanaka T, Yamamoto J, Iwasaki S, 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 U S A. 2003;100:15924–15929.
   PubMed Web of Science ®Google Scholar
• vTv Therapeutics LLC. Use of a PPAR-delta agonist for treating muscle atrophy. US 9487493B2. 2016. (granted patents).
   Google Scholar
• The University of Tolendo. Analogs of peroxisome proliferator activated receptor (PPAR) agonists, and methods of using the same US9695137B2. 2017. (granted patents).
   Google Scholar
• Kim DH, Liu J, Bhat S, et al. Peroxisome proliferator-activated receptor δ agonist attenuates nicotine suppression effect on human mesenchymal stem cell-derived osteogenesis and involves increased expression of heme oxygenase-1. J Bone Miner Metab. 2013;31:44–52.
   PubMed Web of Science ®Google Scholar
• Chan BY, Gartland A, Wilson PJ, et al. PPAR agonists modulate human osteoclast formation and activity in vitro. Bone. 2007;40:149–159.
   PubMed Web of Science ®Google Scholar
• Mosti MP, Stunes AK, Ericsson M, et al. Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW501516 on bone and muscle in ovariectomized rats. Endocrinology. 2014;155:2178–2189.
   PubMed Web of Science ®Google Scholar
• Mitobridge, Inc., Salk Institute for Biological Studies. PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof. US20170304255A1. 2017. (applications).
   Google Scholar
• The Salk Institute for Biological Studies. PPAR agonists and methods of use thereof. US20180305403A1. 2018. (applications).
   Google Scholar
• Mitobridge, Inc. PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof. WO2017180818A1. 2017.
   Google Scholar
• Wu -C-C, Baiga TJ, Downes M, et al. Structural basis for specific ligation of the peroxisome proliferator-activated receptor δ. Proc Natl Acad Sci U S A. 2017;114:E2563–E70.
   PubMed Web of Science ®Google Scholar
• Sohda T, Mizuno K, Tawada H, et al. Studies on antidiabetic agents. I. Synthesis of 5-[4-(2-methyl-2-phenylpropoxy)-benzyl]thiazolidine-2,4-dione (AL-321) and related compounds. Chem Pharm Bull. 1982;30:3563–3573.
   PubMed Web of Science ®Google Scholar
• Cariou B, Charbonnel B, Staels B. Thiazolidinediones and PPARγ agonists: time for a reassessment. Trends Endocrinol Metab. 2012;23:205–215.
   PubMed Web of Science ®Google Scholar
• Metabolic Solutions Development Company, LLC. PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases. US9126959B2. 2015. (granted patents).
   Google Scholar
• Kojun Japan Co., Ltd. PPAR-gamma activator. US9943501B2. 2018. (granted patents).
   Google Scholar
• Tsujino Y. A new agonist for peroxisome proliferation-activated receptor γ (PPARγ), fraglide-1 from zhenjiang fragrant vinegar: screening and characterization based on cell culture experiments. J Oleo Sci. 2017;66:615–622.
   PubMed Web of Science ®Google Scholar
• Theriac Biomedicale Inc. PPAR-gamma activators and their therapeutical usages. US20190000790A1. 2019. (applications)
   Google Scholar
• Vasheghani F, Zhang Y, Li YH, et al. PPARgamma deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage. Ann Rheum Dis. 2015;74:569–578.
   PubMed Web of Science ®Google Scholar
• University of Toronto, União Brasiliense de Educação e Cultura, Fundação Universidade de Brasília. PPAR modulators US20170121268A1. 2017. (applications).
   Google Scholar
• Fraunhofer Gesellschaft zur Förderung der Angewandten Forschung e. V. Competitive PPAR-gamma antagonists. US20170210711A1. 2017. (applications).
   Google Scholar
• Knape T, Flesch D, Kuchler L, et al. Identification and characterisation of a prototype for a new class of competitive PPARγ antagonists. Eur J Pharmacol. 2015;755:16–26.
   PubMed Web of Science ®Google Scholar
• Ahren B. DPP-4 inhibition and the path to clinical proof. Front Endocrinol. 2019;10:376.
   PubMed Web of Science ®Google Scholar
• Sanovel Ilac Sanayi VE Ticaret A.S. Pharmaceutical combinations of sitagliptin and PPAR agonists. WO2016066666A1. 2016.
   Google Scholar
• Sanovel Ilac Sanayi VE Ticaret A.S. Pharmaceutical combinations of vildagliptin and PPAR agonists WO2016066668A1. 2016.
   Google Scholar
• Wang B, Sun Y, Sang Y, et al. Comparison of dipeptidyl peptidase-4 inhibitors and pioglitazone combination therapy versus pioglitazone monotherapy in type 2 diabetes: a system review and meta-analysis. Medicine (Baltimore). 2018;97:e12633.
   PubMed Web of Science ®Google Scholar
• Janssen Pharmaceutica NV. Drug combinations comprising a DGAT inhibitor and a PPAR-agonist. US20180028660A1. 2018. (applications).
   Google Scholar
• Smith SJ, Cases S, Jensen DR, et al. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet. 2000;25:87–90.
   PubMed Web of Science ®Google Scholar
• Sakurai R, Lee C, Shen H, et al. A combination of the aerosolized PPAR-γ agonist pioglitazone and a synthetic surfactant protein B peptide mimic prevents hyperoxia-induced neonatal lung injury in rats. Neonatology. 2018;113:296–304.
   PubMed Web of Science ®Google Scholar
• Los Angeles Biomedical Research Institute at Harbor - UCLA Medical Center. Compositions and methods for administering PPARγ agonists, surfactant peptides and phospholipids. WO2017155857A1. 2017.
   Google Scholar
• Loomba R, Kayali Z, Noureddin M, et al. GS-0976 reduces hepatic steatosis and fibrosis markers in patients with nonalcoholic fatty liver disease. Gastroenterology. 2018;155:1463–73 e6.
   PubMed Web of Science ®Google Scholar
• Genfit. Combination comprising a PPAR agonist such as elafibranor and an acetyl-CoA carboxylase (ACC) inhibitor. WO2018193007A1. 2018.
   Google Scholar
• Genfit. Combination of a PPAR agonist with a FXR agonist. WO2018153933A1. 2018.
   Google Scholar
• Makishima M, Okamoto AY, Repa JJ, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284:1362–1365.
   PubMed Web of Science ®Google Scholar
• Li T, Chiang JY. Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev. 2014;66:948–983.
   PubMed Web of Science ®Google Scholar
• Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–965.
   PubMed Web of Science ®Google Scholar
• Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375:631–643.
   PubMed Web of Science ®Google Scholar
• Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest. 2006;116:607–614.
   PubMed Web of Science ®Google Scholar
• Hong C, Tontonoz P. Liver X receptors in lipid metabolism: opportunities for drug discovery. Nat Rev Drug Discov. 2014;13:433–444.
   PubMed Web of Science ®Google Scholar
• A-Gonzalez N, Bensinger SJ, Hong C, et al. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity. 2009;31:245–258.
   PubMed Web of Science ®Google Scholar
• Washington University, St. Jude Children’s Research Hospital. PPAR agonist or LXR agonist for use in the treatment of systemic lupus erythematosus by modulation of LAP activity. US20190145961A1. 2017. (applications).
   Google Scholar
• Green DR, Oguin TH, Martinez J. The clearance of dying cells: table for two. Cell Death Differ. 2016;23:915–926.
   PubMed Web of Science ®Google Scholar
• Mirza AZ, Althagafi II, Shamshad H. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. Eur J Med Chem. 2019;166:502–513.
   PubMed Web of Science ®Google Scholar
• Support-Venture GmbH. Pharmaceutical combinations for treating cancer US20190160072A1. 2019. (applications).
   Google Scholar
• Mitobridge, Inc. PPAR-alpha agonists for treating mitochondrial diseases. WO2017044551A1. 2017.
   Google Scholar
• University of Illinois. PPAR-alpha agonist treatment of neuropsychiatric disorders. US20180369171A1. 2018. (applications).
   Google Scholar
• Locci A, Pinna G. Stimulation of peroxisome proliferator-activated receptor-alpha by N-palmitoylethanolamine engages allopregnanolone biosynthesis to modulate emotional behavior. Biol Psychiatry. 2019;85:1036–1045.
   PubMed Web of Science ®Google Scholar
• University of South Florida. Combination therapy for traumatic brain injury US20180338996A1. 2018. (applications).
   Google Scholar
• Das M, Leonardo CC, Rangooni S, et al. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats. J Neuroinflammation. 2011;8:148.
   PubMed Web of Science ®Google Scholar
• Sauerbeck A, Gao J, Readnower R, et al. Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. Exp Neurol. 2011;227:128–135.
   PubMed Web of Science ®Google Scholar
• Neuro Via, Inc. Methods and compositions for treating demyelinating diseases using sobetirome or a sobetirome prodrug and a PPAR activator. US20180353450A1. 2018. (applications).
   Google Scholar
• The University of North Carolina at Chapel Hill. Methods of treating methicillin-resistant Staphylococcus aureus (MRSA) using PPAR-gamma agonists US20150328198A1. 2015. (applications).
   Google Scholar
• Thurlow LR, Joshi GS, Clark JR, et al. Functional modularity of the arginine catabolic mobile element contributes to the success of USA300 methicillin-resistant Staphylococcus aureus. Cell Host Microbe. 2013;13:100–107.
   PubMed Web of Science ®Google Scholar
• Thurlow LR, Joshi GS, Richardson AR. Peroxisome proliferator-activated receptor γ is essential for the resolution of Staphylococcus aureus skin infections. Cell Host Microbe. 2018;24:261–70.e4.
   PubMed Web of Science ®Google Scholar
• Cadila Healthcae Ltd. Dual PPAR modulators for the treatment of diabetic retinopathy and diabetic eye diseases WO2017089980A1. 2017.
   Google Scholar
• Cadila Healthcare Ltd. Dual PPAR modulators for the treatment of diabetic nephropathy and related diseases WO2017089979A1. 2017.
   Google Scholar
• Ciudin A, Hernandez C, Simo R. Molecular implications of the PPARs in the diabetic eye. PPAR Res. 2013;2013:686525.
   PubMedGoogle Scholar
• Kouroumichakis I, Papanas N, Zarogoulidis P, et al. Fibrates: therapeutic potential for diabetic nephropathy? Eur J Intern Med. 2012;23:309–316.
   PubMed Web of Science ®Google Scholar
• Jia Z, Sun Y, Yang G, et al. New insights into the PPARγ agonists for the treatment of diabetic nephropathy. PPAR Res. 2014;2014:818530.
   PubMedGoogle Scholar
• Inventiva. PPAR compounds for use in the treatment of fibrotic diseases. US20180333396A1. 2018. (applications).
   Google Scholar
• Boubia B, Poupardin O, Barth M, et al. Design, synthesis, and evaluation of a novel series of indole sulfonamide peroxisome proliferator activated receptor (PPAR) α/γ/δ triple activators: discovery of lanifibranor, a new antifibrotic clinical candidate. J Med Chem. 2018;61:2246–2265.
   PubMed Web of Science ®Google Scholar
• Ruzehaji N, Frantz C, Ponsoye M, et al. Pan PPAR agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis. Ann Rheum Dis. 2016;75:2175–2183.
   PubMed Web of Science ®Google Scholar
• Avouac J, Konstantinova I, Guignabert C, et al. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension. Ann Rheum Dis. 2017;76:1931–1940.
   PubMed Web of Science ®Google Scholar
• InteKrin Therapeutics, Inc. PPAR-gamma agonist for treatment of bone disorders. US20190167660A1. 2019. (applications).
   Google Scholar
• Higgins LS, Mantzoros CS. The development of INT131 as a selective PPARγ modulator: approach to a safer insulin sensitizer. PPAR Res. 2008;2008:936906.
   PubMed Web of Science ®Google Scholar
• Motani A, Wang Z, Weiszmann J, et al. INT131: a selective modulator of PPARγ. J Mol Biol. 2009;386:1301–1311.
   PubMed Web of Science ®Google Scholar
• DePaoli AM, Higgins LS, Henry RR, et al. Can a selective PPARγ modulator improve glycemic control in patients with type 2 diabetes with fewer side effects compared with pioglitazone? Diabetes Care. 2014;37:1918.
   PubMed Web of Science ®Google Scholar
• Lee DH, Huang H, Choi K, et al. Selective PPARγ modulator INT131 normalizes insulin signaling defects and improves bone mass in diet-induced obese mice. Am J Physiol Endocrinol Metab. 2012;302:E552–60.
   PubMed Web of Science ®Google Scholar
• Support-Venture GmbH. Method of preventing or treating hearing loss. US20180021320A1. 2018. (applications)
   Google Scholar
• Sekulic-Jablanovic M, Petkovic V, Wright MB, et al. Effects of peroxisome proliferator activated receptors (PPAR)- γ and -α agonists on cochlear protection from oxidative stress. PLoS One. 2017;12:e0188596.
   PubMed Web of Science ®Google Scholar
• Indiana University Research and Technology Corporation. Lysosomal acid lipase and PPAR gamma ligands as immune therapies for cancer treatment. US20190076508A1. 2019. (applications).
   Google Scholar
• Yan C, Zhao T, Du H. Lysosomal acid lipase in cancer. Oncoscience. 2015;2:727–728.
   PubMedGoogle Scholar
• Peraza MA, Burdick AD, Marin HE, et al. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicol Sci. 2006;90:269–295.
   PubMed Web of Science ®Google Scholar
• Hedrington MS, Davis SN. Peroxisome proliferator-activated receptor refalpha-mediated drug toxicity in the liver. Expert Opin Drug Metab Toxicol. 2018;14:671–677.
   PubMed Web of Science ®Google Scholar
• Preiss D, Tikkanen MJ, Welsh P, et al. Lipid-modifying therapies and risk of pancreatitis: a meta-analysis. JAMA. 2012;308:804–811.
   PubMed Web of Science ®Google Scholar
• Mackenzie LS, Lione L. Harnessing the benefits of PPARβ/δ agonists. Life Sci. 2013;93:963–967.
   PubMed Web of Science ®Google Scholar
• Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med. 1998;338:916–917.
   PubMed Web of Science ®Google Scholar
• Tentolouris A, Vlachakis P, Tzeravini E, et al. SGLT2 inhibitors: a review of their antidiabetic and cardioprotective effects. Int J Environ Res Public Health. 2019;16.
   PubMed Web of Science ®Google Scholar
• Alawad AS, Levy C. FXR agonists: from bench to bedside, a guide for clinicians. Dig Dis Sci. 2016;61:3395–3404.
   PubMed Web of Science ®Google Scholar
• Han CY. Update on FXR biology: promising therapeutic target? Int J Mol Sci. 2018;19.
   Web of Science ®Google Scholar
• Steffensen KR, Jakobsson T, Gustafsson JA. Targeting liver X receptors in inflammation. Expert Opin Ther Targets. 2013;17:977–990.
   PubMed Web of Science ®Google Scholar