Liver X receptor modulators: A review of recently patented compounds (2009-2012)

Expert Opinion on Therapeutic Patents

Volumn 23, Issue 10, 2013, Pages 1317-1335

  Loren, Jon ^a   Huang, Zhihong ^a   Laffitte, Bryan A ^a   Molteni, Valentina ^a  

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

Author keywords

Atherosclerosis; ATP binding cassette transporter A1; Cardiovascular diseases; Liver X receptor; Reverse cholesterol transport; Triglyceride

Indexed keywords

ABC TRANSPORTER A1; ABC TRANSPORTER G1; ANTIINFLAMMATORY AGENT; BIOLOGICAL MARKER; BMS 779788; BMS 852927; CS 8080; HYDANTOIN DERIVATIVE; IMIDAZOLIDINE DERIVATIVE; INTERLEUKIN 6; LIGAND; LIVER X RECEPTOR AGONIST; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LXR 623; METHANOL DERIVATIVE; N (2,2,2 TRIFLUOROETHYL) N [4 (2,2,2 TRIFLUORO 1 HYDROXY 1 TRIFLUOROMETHYLETHYL)PHENYL]BENZENESULFONAMIDE; OXYSTEROL; PARTIAL AGONIST; PIPERAZINE DERIVATIVE; QUINAZOLINE; QUINOLINE; QUINOXALINE DERIVATIVE; STEROID; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; UNCLASSIFIED DRUG;

AGARICUS SUBRUFESCENS; ANTIINFLAMMATORY ACTIVITY; ATHEROSCLEROSIS; ATOPIC DERMATITIS; BASAL CELL CARCINOMA; BLADDER CANCER; CARDIOVASCULAR DISEASE; CARTILAGE DEGENERATION; CHOLESTEROL METABOLISM; CONNECTIVE TISSUE DISEASE; CRYSTAL STRUCTURE; DIFFERENTIAL SCANNING CALORIMETRY; DRUG SAFETY; DRUG TOLERABILITY; DYSLIPIDEMIA; GENE CONTROL; GENE EXPRESSION; GENE INDUCTION; GENE TARGETING; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; INFLAMMATION; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; LEUKEMIA; LIGAND BINDING; LIPID METABOLISM; MELANOMA; METABOLIC DISORDER; MULTIPLE MYELOMA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OSTEOARTHRITIS; OVARY CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHYSICAL CHEMISTRY; PROSTATE CANCER; PSORIASIS; RESTENOSIS; REVIEW; RHEUMATOID ARTHRITIS; SKIN DISEASE; SKIN INJURY; STOMACH CANCER; TENDINITIS; THERMOGRAVIMETRY; UPREGULATION; X RAY;

ANIMALS; ATHEROSCLEROSIS; DRUG APPROVAL; DRUG INDUSTRY; HUMANS; LIPID METABOLISM; LIPOGENESIS; LIVER; ORPHAN NUCLEAR RECEPTORS; PATENTS AS TOPIC;

EID: 84884570398     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2013.814640     Document Type: Review

References (134)

1. Kalaany NY, Mangelsdorf DJ. LXRs and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol 2006;68:159-91
2. Tontonoz P, Mangelsdorf DJ. Liver x receptor signaling pathways in cardiovascular disease. Mol Endocrinol 2003;17:985-93 (Pubitemid 36683707)
3. Janowski BA, Willy PJ, Devi TR, et al. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 1996;383:728-31 (Pubitemid 26360651)
4. Lehmann JM, Kliewer SA, Moore LB, et al. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem 1997;272:3137-40 (Pubitemid 27066798)
5. Perissi V, Aggarwal A, Glass CK, et al. A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors. Cell 2004;116:511-26 (Pubitemid 38264429)
6. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000;14:121-41 (Pubitemid 30070977)
7. McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 2002;108:465-74 (Pubitemid 34260872)
8. Rosenfeld MG, Glass CK. Coregulator codes of transcriptional regulation by nuclear receptors. J Biol Chem 2001;276:36865-8
9. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995;377:454-7
10. Horlein AJ, Na?a?r AM, Heinzel T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995;377:397-404
11. Joseph SB, Castrillo A, Laffitte BA, et al. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 2003;9:213-19 (Pubitemid 36227724)
12. Hoberg JE, Yeung F, Mayo MW. SMRT derepression by the IkB kinase a: a prerequisite to NF-kB transcription and survival. Mol Cell 2004;16:245-55 (Pubitemid 39388839)
13. Ogawa S, Lozach J, Jepsen K, et al. A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation. Proc Natl Acad Sci 2004;101:14461-6 (Pubitemid 39346771)
14. Pascual G, Fong AL, Ogawa S, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-g. Nature 2004;437:759-63 (Pubitemid 41486547)
15. Ghisletti S, Huang W, Ogawa S, et al. Parallel SUMOylationdependent pathways mediate gene- and signal-specific transrepression by LXRs and PPAR g. Mol Cell 2007;25:57-70 (Pubitemid 46049061)
16. Peet DJ, Turley SD, Ma W, et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 1998;93:693-704 (Pubitemid 28257577)
17. Alberti S, Schuster G, Parini P, et al. Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice. J Clin Invest 2001;107:565-73 (Pubitemid 32206188)
18. Venkateswaran A, Laffitte BA, Joseph SB, et al. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci USA 2000;97:12097-102
19. Chawla A, Boisvert WA, Lee CH, et al. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell 2001;7:161-71 (Pubitemid 32162909)
20. Costet P, Luo Y, Wang N, et al. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 2000;275:28240-5
21. Laffitte BA, Repa JJ, Joseph SB, et al. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci USA 2001;98:507-12 (Pubitemid 32105072)
22. Repa JJ, Turley SD, Lobaccaro JA, et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 2000;289:1524-9
23. Bodzioch M, Orsó E, Klucken J, et al. The gene encoding ATP binding cassette transporter 1 is mutated in Tangier disease. Nat Genet 1999;22:347-51 (Pubitemid 29369524)
24. Brooks-Wilson A, Marcil M, Clee SM, et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 1999;22:336-45 (Pubitemid 29369523)
25. Rust S, Rosier M, Funke H, et al. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet 1999;22:352-5 (Pubitemid 29369525)
26. Curtiss LK, Boisvert WA. Apolipoprotein E and atherosclerosis. Curr Opin Lipidol 2000;11:243-51 (Pubitemid 30336021)
27. Spann NJ, Garmire LX, McDonald JG, et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 2012;151:138-52
28. Tangirala RK, Bischoff ED, Joseph SB, et al. Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc Natl Acad Sci USA 2002;99:11896-901 (Pubitemid 34994495)
29. Schuster GU, Parini P, Wang L, et al. Accumulation of foam cells in liver X receptor-deficient mice. Circulation 2002;106:1147-53 (Pubitemid 34970858)
30. Repa JJ, Berge KE, Pomajzl C, et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002;277:18793-800 (Pubitemid 34952438)
31. Yu L, York J, von Bergmann K, et al. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem 2003;278:15565-70 (Pubitemid 36799664)
32. Berge KE, Tian H, Graf GA, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000;29:1771-5 (Pubitemid 32004809)
33. Allayee H, Laffitte BA, Lusis AJ. An absorbing study of cholesterol. Science 2000;290:1709-11 (Pubitemid 32004791)
34. Lee MH, Lu K, Hazard S, et al. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet 2001;27:79-83 (Pubitemid 32044523)
35. Naik SU, Wang X, Da Silva JS, et al. Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation 2006;113:90-7 (Pubitemid 43958493)
36. Bradley MN, Hong C, Chen M, et al. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J Clin Invest 2007;117:2337-46 (Pubitemid 47219578)
37. Schultz JR, Tu H, Luk A, et al. Role of LXRs in control of lipogenesis. Genes Dev 2000;14:2831-8
38. Repa JJ, Liang G, Ou J, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 2000;14:2819-30
39. Joseph SB, Laffitte BA, Patel PH, et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem 2002;277:11019-25 (Pubitemid 34952859)
40. Grefhorst A, Elzinga BM, Voshol PJ, et al. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem 2002;277:34182-90
41. Laffitte BA, Joseph SB, Chen M, et al. The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions. Mol Cell Biol 2003;23:2182-91 (Pubitemid 36278826)
42. Groot PH, Pearce NJ, Yates JW, et al. Synthetic LXR agonists increase LDL in CETP species. J Lipid Res 2005;46:2182-91 (Pubitemid 41377470)
43. Joseph SB, Castrillo A, Laffitte BA, et al. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 2003;9:213-19 (Pubitemid 36227724)
44. Castrillo A, Joseph SB, Marathe C, et al. Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. J Biol Chem 2003;278:10443-9 (Pubitemid 36800310)
45. Terasaka N, Hiroshima A, Ariga A, et al. Liver X receptor agonists inhibit tissue factor expression in macrophages. FEBS J 2005;272:1546-56 (Pubitemid 40444942)
46. Ogawa D, Stone J, Takata Y, et al. Liver X receptor agonists inhibit cytokine-induced osteopontin expression in macrophages through interference with activator protein-1 signaling pathways. Circ Res 2005;96:e59-67
47. Fowler AJ, Sheu MY, Schmuth M, et al. Liver X receptor activators display anti-inflammatory activity in irritant and allergic contact dermatitis models: liver-X receptor-specific inhibition of inflammation and primary cytokine production. J Invest Dermatol 2003;120:246-55 (Pubitemid 36513075)
48. Castrillo A, Joseph SB, Vaidya SA, et al. Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell 2003;12:805-16 (Pubitemid 37352775)
49. Joseph SB, Bradley MN, Castrillo A, et al. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 2004;119:299-309 (Pubitemid 39360910)
50. Valledor AF, Hsu LC, Ogawa S, et al. Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis. Proc Natl Acad Sci USA 2004;101:17813-18 (Pubitemid 40051969)
51. 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;31:245-58
52. Bensinger SJ, Bradley MN, Joseph SB, et al. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 2008;134:97-111 (Pubitemid 351905740)
53. Lusis AJ. Atherosclerosis. Nature 2000;407:233-41
54. Fan J, Watanabe T. Inflammatory reactions in the pathogenesis of atherosclerosis. J Atheroscler Thromb 2003;10:63-71
55. Joseph SB, McKilligin E, Pei L, et al. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 2002;99:7604-9 (Pubitemid 34568738)
56. Levin N, Bischoff ED, Daige CL, et al. Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. Arterioscler Thromb Vasc Biol 2005;25:135-42 (Pubitemid 40054266)
57. Bradley MN, Hong C, Chen M, et al. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J Clin Invest 2007;117:2337-46 (Pubitemid 47219578)
58. Bischoff ED, Daige CL, Petrowski M, et al. Non-redundant roles for LXRalpha and LXRbeta in atherosclerosis susceptibility in low density lipoprotein receptor knockout mice. J Lipid Res 2010;51:900-6
59. Verschuren L, de Vries-van der Weij J, Zadelaar S, et al. LXR agonist suppresses atherosclerotic lesion growth and promotes lesion regression in apoE 3Leiden mice: time course and mechanisms. J Lipid Res 2009;50:301-11
60. Hong C, Bradley MN, Rong X, et al. LXRa is uniquely required for maximal reverse cholesterol transport and atheroprotection in ApoE-deficient mice. J Lipid Res 2012;53:1126-33
61. Feig JE, Pineda-Torra I, Sanson M, et al. LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression. J Clin Invest 2010;120:4415-24
62. Srivastava RA. Evaluation of anti-Atherosclerotic activities of PPAR-A, PPAR-g, and LXR agonists in hyperlipidemic atherosclerosis-susceptible F(1)B hamsters. Atherosclerosis 2011;214:86-93
63. Honzumi S, Shima A, Hiroshima A, et al. Synthetic LXR agonist inhibits the development of atherosclerosis in New Zealand White rabbits. Biochim Biophys Acta 2011;1811:1136-45
64. Laffitte BA, Chao LC, Li J, et al. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci USA 2003;100:5419-24 (Pubitemid 36542720)
65. Cao G, Liang Y, Broderick CL, et al. Antidiabetic action of a liver x receptor agonist mediated by inhibition of hepatic gluconeogenesis. J Biol Chem 2003;278:1131-6 (Pubitemid 36790794)
66. Commerford SR, Vargas L, Dorfman SE, et al. Dissection of the insulin-sensitizing effect of liver X receptor ligands. Mol Endocrinol 2007;21:3002-12 (Pubitemid 350223510)
67. Ogihara T, Chuang JC, Vestermark GL, et al. Liver X receptor agonists augment human islet function through activation of anaplerotic pathways and glycerolipid/free fatty acid cycling. J Biol Chem 2010;285:5392-404
68. Koldamova RP, Lefterov IM, Staufenbiel M, et al. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem 2005;280:4079-88 (Pubitemid 40288571)
69. Zelcer N, Khanlou N, Clare R, et al. Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. Proc Natl Acad Sci USA 2007;104:10601-6 (Pubitemid 47185711)
70. Jiang Q, Lee CY, Mandrekar S, et al. ApoE promotes the proteolytic degradation of Abeta. Neuron 2008;58:681-93 (Pubitemid 351778466)
71. Fitz NF, Cronican A, Pham T, et al. Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice. J Neurosci 2010;30:6862-72
72. Vanmierlo T, Rutten K, Dederen J, et al. Liver X receptor activation restores memory in aged AD mice without reducing amyloid. Neurobiol Aging 2011;32:1262-72
73. Dai YB, Tan XJ, Wu WF, et al. Liver X receptor b protects dopaminergic neurons in a mouse model of Parkinson disease. Proc Natl Acad Sci USA 2012;109:13112-17
74. Loane DJ, Washington PM, Vardanian L, et al. Modulation of ABCA1 by an LXR agonist reduces b-Amyloid levels and improves outcome after traumatic brain injury. J Neurotrauma 2011;28:225-36
75. Namjoshi DR, Martin G, Donkin J, et al. The liver X receptor agonist GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E. PLoS One 2013;8:e53529
76. Guo D, Reinitz F, Youssef M, et al. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discov 2011;1:442-56
77. Katz A, Udata C, Ott E, et al. Safety, pharmacokinetics, and pharmacodynamics of single doses of LXR-623, a novel liver X-receptor agonist, in healthy participants. J Clin Pharm 2009;49:643-9
78. Effects of Multiple Doses of CS-8080 in Healthy Volunteers, NCT00796575. 2008. Available from: clinicaltrials.gov
79. Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-779788 in Healthy Subjects, NCT00836602. 2008. Available from: clinicaltrials.gov
80. A Safety Study of BMS-852927 in Subjects With Hypercholesterolemia, NCT01651273. 2012. Available from: clinicaltrials.gov
81. Bernotas RC, Singhaus RR, Kaufman DH, et al. 4-(3-Aryloxyaryl) quinoline sulfones are potent liver X receptor agonists. Bioorg Med Chem Lett 2010;20:209-12
82. Singhaus RR, Bernotas RC, Steffan R, et al. 3-(3-Aryloxyaryl)imidazo[1,2- A] pyridine sulfones as liver X receptor agonists. Bioorg Med Chem Lett 2010;20:521-5
83. Travins JM, Bernotas RC, Kaufman DH, et al. 1-(3-Aryloxyaryl) benzimidazole sulfones are liver X receptor agonists. Bioorg Med Chem Lett 2010;20:526-30
84. Hu B, Bernotas RC, Unwalla R, et al. Quinoline-3-carboxyamide containing sulfones as liver X receptor (LXR) agonists with binding selectivity for LXRb and low blood-brain penetration. Bioorg Med Chem Lett 2010;20:689-93
85. Ullrich JW, Morris R, Bernotas RC, et al. Synthesis of 4-(3-biaryl)quinoline sulfones as potent liver X receptor agonsit. Bioorg Med Chem Lett 2010;20:2903-7
86. Wyeth. Quinoline compounds. WO2008049047
87. Wyeth. Quinoxaline-based LXR modulators. WO2010054229
88. Wyeth. Polar quinazolines as liver X receptors (LXRs) modulators. WO2010059627
89. Wyeth. Novel quinoline esters useful for treating skin disorders. WO2012004748
90. Hu B, Unwalla RJ, Goljer I, et al. Identification of phenylsulfonesubstituted quinoxaline (WYE-672) as a tissue selective liver x-receptor (LXR) agonist. J Med Chem 2010;53:3296-304
91. Wyeth. Quinazoline compounds. WO2009020683
92. Bodor, NS. Inactive metabolite approach to soft drug design. US6610675
93. Kowa. 2-Oxochromene derivatives. WO2009107387, (US2009286780
94. Kowa. 1,3-Dihydroisobenzofuran derivatives. WO2009122707, (US7951822)
95. Kowa. Quinoline compounds. WO2009133692, (US8008306)
96. Kowa. Carbinol derivatives having cyclic linkers. WO2009144961, (US8153634)
97. Kowa. Carbinol derivatives having heterocyclic linkers. WO2010125811, (US2010280013)
98. Kowa. Substituted carbinol compounds. WO2008065754
99. Hu B, Quinet E, Unwalla R, et al. Carboxylic acid based quinolines as liver X receptor modulators that have LXRb receptor binding selectivity. Bioorg Med Chem Lett 2008;18:54-9
100. Exelixis. LXR modulators. WO2010138598
101. Exelixis. Imidazole based LXR modulators. WO2007002563
102. Exelixis. Prodrugs of LXR modulating imidazole derivatives. WO2012135082
103. NV Organon. 1-(4-Ureidobenzoyl) piperazine derivatives. WO2010025179
104. NV Organon. N-benzyl N'-Arylcarbonylpiperazine derivatives as LXR modulators. WO2009024550
105. NV Organon. N-(1,1,1,3,3,3- Hexafluoro-2-hydroxypropan-2-yl) benzyl-N'-Arylcarbonylpiperazine derivatives. WO2009138438
106. NV Organon. (1,1,1,3,3,3-Hexafluoro-2- hydroxypropan-2-yl) phenyl derivatives, pharmaceutical compositions thereof and their use for the treatment of atherosclerosis. WO2011051282
107. Hoffmann - La Roche. Imidazolidine derivatives. WO2009150109
108. Hoffmann - La Roche. Imidazolidinone derivatives. WO2008119657
109. Hoffmann - La Roche. Novel piperazine amide derivatives. WO2009021868
110. Galderma. Ligands that modulate LXR-type receptors. WO2004076418
111. Galderma. Novel hexafluoro- 2-biphenylisopropanol compounds that modulate LXR-type receptors, process for the preparation thereof and use thereof as medicaments in human and veterinary medicine and also in cosmetics. WO2010023317
112. Intermed. Terpenoid Spirol Ketal Compounds with LXR Agonists Activity, Their Use and Formulations with Them. WO2012079721
113. Su ZY, Tung YC, Hwang LS, et al. Blazeispirol A from agaricus blazei fermentation product induces cell death in human hepatoma Hep 3B cells through caspase-dependent and caspase-independent pathways. J Agric Food Chem 2011;59:5109-16
114. Peng D, Hiipakka RA, Dai Q, et al. Anitatherosclerotic effects of a novel synthetic tissue-selective steroidal liver X receptor agonist in low-density lipoprotein receptor-deficient mice. J Pharmacol Exp Ther 2008;327(2):332-42
115. University of Chicago. Liver X Receptor Agonists. WO2011014661
116. Sclole DR, Xu X, Wang H, et al. Liver X Receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein. Gynecol Oncol 2010;116:109-16
117. University of California, Los Angeles. Oxysterols that Activate Liver X Receptor Signaling and Inhibit Hedgehog Signaling. WO2011103175
118. Watanabe B, Nakagawa Y, Ogura T, et al. Stereoselective synthesis of (22R)- and (22S)-castasterone/ponasterone A hybrid compounds and evaluation of their molting hormone activity. Steroids 2004;69:483-93 (Pubitemid 38898739)
119. University of California, Los Angeles. Inhibition of PPAR Gamma Expression by Specific Osteogenic Oxysterols. WO2008082520
120. University of Tokyo. Tricyclic Compound. WO2009107389
121. Aoyama A, Endo-Umeda K, Kishida K, et al. Design, synthesis, and biological evaluation of novel transrepression-selective liver X receptor (LXR) ligands with 5,11-Dihydro-5- methyl-11-methylene-6H-dibenz[b,e] azepin-6-one skeleton. J Med Chem 2012;55:7360-77
122. Motoshima K, Noguchi-Yachide T, Sugita K, et al. Separation of a-glucosidase-inhibitory and liver X receptor-Antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRa-selective antagonist. Bioorg Med Chem 2009;17:5001-14
123. Zuercher WJ, Buckholz RG, Campobasso N, et al. Discovery of tertiary sulfonamides as potent liver X receptor antagonists. J Med Chem 2010;53:3412-16
124. Griffett K, Solt LA, El-Gendy BEM, et al. A liver-selective LXR inverse agonist that suppresses hepatic steatosis. ACS Chem Biol 2013;8:559-67
125. Chao EY, Caravella JA, Watson MA, et al. Structure-guided design of N-phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity. J Med Chem 2008;51:5758-65
126. SNU R&DB Foundation. Ajoene for preventing and treating diseases caused by LXR a overexpression. WO2011122805
127. SNU R&DB Foundation. Liquiritigenin and isoliquiritigenin for treating diseases caused by over-expression of LXRa or SREBP-1. WO2011102695
128. SNU R&DB Foundation. Saururus chinensis extract and for preventing and treating diseases caused by overexpression of LXRa. WO2011034362
129. SNU R&DB Foundation. Sesterterpene Compounds and Use Thereof. WO2012033353
130. SNU R&DB Foundation. Pharmaceutical Composition Containing 1,2-Dithiolthione Derivative for Preventing or Treating Disease Caused by Overexpression of LXRalpha. WO2010016681
131. SNU R&DB Foundation. LXRa Inhibitors for Preventing and Treating Fatty Liver. KR2012058677
132. SNU R&DB Foundation. Prophylactic and therapeutic use of oltipraz as an antifibrotic and anticirrhotic agent in the liver and pharmaceutical composition containing oltipraz. KR20100404303, (WO0176604
133. SNU R&DB Foundation. Pharmaceutical compositions for the treatment or prevention of obesity. KR20100576157
134. SNU R&DB Foundation. The use of direct activation by organic agents of p90 ribosomal s6 kinase 1 (rsk1) for prevention and treatment of diabetes, obesity and metabolic syndrome. KR20100590818