An update on non-steroidal liver X receptor agonists and their potential use in the treatment of atherosclerosis

Bibliography

• BENNETT DJ, COOKE AJ, EDWARDS AS, MOIR E, RAY PC: Liver X receptor agonists as a treatment for atherosclerosis. Expert Opin. Ther. Patents (2004) 14(7):967-982.
   Web of Science ®Google Scholar
• COLLINS JL: Therapeutic opportunities for liver X receptor modulators. Curr. Opin. Drug Disc. & Dev. (2004) 7(5):692-702.
   PubMed Web of Science ®Google Scholar
• JOSEPH SB, TONTONOZ P: LXRs: new therapeutic targets in atherosclerosis? Curr. Opin. Pharm. (2003) 3(2):192-197.
   PubMed Web of Science ®Google Scholar
• KALAANY NY, MANGELSDORFF DJ: LXRs and FXR: the yin and yang of cholesterol and fat metabolism. Annu. Rev. Physiol. (2006) 68:159-191.
   PubMed Web of Science ®Google Scholar
• WILLIAMS S, BLEDSOE RK, COLLINS JL et al.: X-Ray crystal structure of the liver X receptor β ligand binding domain: regulation by a histidine– tryptophan switch. J. Biol. Chem. (2003) 278(29):27138-27143.
   PubMed Web of Science ®Google Scholar
• SVENSSON S, ÖSTBERG T, JACOBSSON M et al.: Crystal structure of the heterodimeric complex of LXRα and RXRβ ligand-binding domains in a fully agonist conformation. EMBO (2003) 22(18):4625-4633.
   PubMed Web of Science ®Google Scholar
• FARNEGARDH M, BONN T, SUN S et al.: The three-dimensional structure of the liver X receptor β reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands. J. Biol. Chem. (2003) 278(40):38821-38828.
   PubMed Web of Science ®Google Scholar
• HOERER S, SCHMID A, HECKEL A, BUDZINSKI R-M, NAR H: Crystal structure of the human liver receptor β ligand-binding domain in complex with a synthetic agonist. J. Mol. Biol. (2003) 334(5):853-861.
   PubMedGoogle Scholar
• LI L, LIU J, ZHU L et al.: Discovery and optimisation of a novel series of liver X receptor-α agonists. Bioorg. Med. Chem. Lett. (2006) 16(6):1638-1642.
   PubMedGoogle Scholar
• SCHULTZ JR, TU H, LUK A et al.: Role of LXRs in control of lipogenesis. Genes Dev. (2000) 14(22):2831-2838.
   PubMed Web of Science ®Google Scholar
• HOUCK KA, BORCHER KM, HEPLER CD et al.: T0901317 is a dual LXR/FXR agonist. Mol. Genet. Metab. (2004) 83(1/2):184-187.
   PubMed Web of Science ®Google Scholar
• SHENOY SD, SPENCER TA, MERCER-HAINE NA et al.: CYP3A induction by liver X receptor ligands in primary cultured rat and mouse hepatocytes is mediated by the pregnane X receptor. Drug Metab. Dispos. (2004) 32(1):66-71.
   PubMed Web of Science ®Google Scholar
• TERASAKA N, HIROSHIMA A, ARIGA A et al.: Liver X receptor agonists inhibit tissue factor expression in macrophages. FEBS J. (2005) 272(6):1546-1556.
   PubMed Web of Science ®Google Scholar
• GIACHELLI CM, BAE N, ALMEIDA M, DENHARD DT, ALPERS CE, SCHWARTZ SM: Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques. J. Clin. Invest. (1993) 92(4):1686-1696.
   PubMed Web of Science ®Google Scholar
• BRUEMMER D, COLLINS AR, NOH G et al.: Angiotensin II accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin deficient mice. J. Clin. Invest. (2003) 112(9):1318-1331.
   PubMed Web of Science ®Google Scholar
• WEBER GF, ZAWAIDEH S, HIKITA S, KUMAR VA, CANTOR H, ASHKAR S: Phosphorylation dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. J. Leukoc. Biol. (2002) 72(4):752-761.
   PubMed Web of Science ®Google Scholar
• OGAWA D, STONE JF, 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(7):e59-e67.
   PubMed Web of Science ®Google Scholar
• COSTET P, CARIOU B, LAMBERT G et al.: Hepatic PCKS9 expression is regulated by nutritional status via insulin and sterol regulatory element binding protein 1c. J. Biol. Chem. (2006) 281(10):6211-6218.
   PubMed Web of Science ®Google Scholar
• DUVAL C, TOUCHE V, TAILLEUX A et al.: Niemann–Pick C1-like gene expression is down-regulated by LXR activators in the intestine. Biochem. Biophys. Res. Commun. (2006) 340(4):1259-1263.
   PubMed Web of Science ®Google Scholar
• RIGAMONTI E, HELIN L, LESTAVEL S et al.: Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Circ. Res. (2005) 97(7):682-689.
   PubMed Web of Science ®Google Scholar
• WANG N, RANALLETTA M, MATSUURA F, PENG F, TALL AR: LXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhances cholesterol efflux to HDL. Arterioscler. Thromb. Vasc. Biol. (2006) 26(6):1310-1316.
   PubMed Web of Science ®Google Scholar
• HU T, FOXWORTHY P, SIESKY A et al.: Hepatic peroxisomal fatty acid β-oxidation is regulated by liver X receptor α. Endocrinology (2005) 146(12):5380-5387.
   PubMedGoogle Scholar
• NORATA GD, ONGARI M, UBOLDI P, PELLEGATTA F, CATAPANO AL: Liver X receptor and retinoic receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells. International J. Mol. Med. (2005) 16(4):717-722.
   PubMedGoogle Scholar
• 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(1):135-142.
   PubMed Web of Science ®Google Scholar
• COLLINS JL, FIVUSH AM, WATSON MA et al.: Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J. Med. Chem. (2002) 45(10):1963-1966.
   PubMed Web of Science ®Google Scholar
• KRUIT JK, PLOSCH T, HAVINGA R et al.: Increased fecal neutral sterol loss upon liver X receptor activation is independent of biliary sterol secretion in mice. Gastroenterology (2005) 128(1):147-156.
   PubMed Web of Science ®Google Scholar
• QUINET EM, SAVIO DA, HALPERN AR, CHEN L, MILLER CP, NAMBI P: Gene-selective modulation by a synthetic oxysterol ligand of the liver X receptor. J. Lipid. Res. (2004) 45(10):1929-1942.
   PubMed Web of Science ®Google Scholar
• 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(11):7604-7609.
   PubMed Web of Science ®Google Scholar
• WANG M, BRIGGS MR: HDL: the metabolism, function, and therapeutic importance. Chem. Rev. (2004) 104(1):119-137.
   PubMed Web of Science ®Google Scholar
• MIAO B, ZONDLO S, GIBBS S et al.: Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J. Lipid Res. (2004) 45(8):1410-1417.
   PubMed Web of Science ®Google Scholar
• NAIK SU, WANG X, DA SILVA JS et al.: Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation (2006) 113(1):90-97.
   PubMed Web of Science ®Google Scholar
• GROOT PHE, PEARCE NJ, YATES JW et al.: Synthetic LXR agonists increase LDL in CETP species. J. Lipid Res. (2005) 46(10):2182-2191.
   PubMed Web of Science ®Google Scholar
• JAYE MC, KRAWIEC JA, CAMPOBASSO N et al.: Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure. J. Med. Chem. (2005) 48(17):5419-5422.
   PubMed Web of Science ®Google Scholar
• CAIRNS WJ: Design of pathway-selective nuclear receptor modulators, a case study on LXR. Challenges Facing Drug Discovery in Vascular Disease. Newhouse, UK (2005).
   Google Scholar
• SZEWCZYK JW, HUANG S, CHIN J et al.: SAR studies: Designing potent and selective LXR agonists. Bioorg. Med. Chem. Lett. (2006) 16(11):3055-3060.
   PubMedGoogle Scholar
• LUND EG, PETERSON LB, ADAMS AD et al.: Different roles of liver X receptor α and β in lipid metabolism: effects of an α-selective and a dual agonist in mice deficient in each subtype. Biochem. Pharmacol. (2006) 71(4):453-463.
   PubMed Web of Science ®Google Scholar
• SINGH SB, ONDEYKA JG, LIU W et al.: Discovery and development of dimeric podocarpic acid leads as potent agonists of liver X receptor with HDL cholesterol raising activity in mice and hamsters. Bioorg. Med. Chem. Lett. (2005) 15(11):2824-2828.
   PubMedGoogle Scholar
• LIU W, CHEN S, DROPINSKI J et al.: Design, synthesis, and structure–activity relationship of podocarpic acid amides as liver X receptor agonists for potential treatment of atherosclerosis. Bioorg. Med. Chem. Lett. (2005) 15(20):4574-4578.
   PubMedGoogle Scholar
• BERNOTAS RC, SINGHAUS R, NAMBI P et al.: Design and synthesis of novel 3-benzyl-quinolines as LXR modulators. 231st ACS National Meeting. Atlanta, USA (March 26-30, 2006) MED-98.
   Google Scholar
• SINGHAUS Jr. RR, BERNOTAS RC, ULLRICH J et al.: Design and synthesis of 4-aryl-3-methylquinolines as LXR modulators. 231st ACS National Meeting. Atlanta. USA (March 26-30, 2006) MED-102.
   Google Scholar
• JETTER J, BAIHUA H, COLLINI M et al.: Further modification on phenyl acetic acid based quinolines as liver X receptor (LXR) agonists. 231st ACS National Meeting. Atlanta, USA (March 26-30, 2006) MED-101.
   Google Scholar
• COLLINI M, BAIHUA H, JETTER J et al.: Discovery and SAR of phenyl-acetic acid based quinolines as liver X receptor (LXR) agonists. 231st ACS National Meeting. Atlanta, USA (March 26-30, 2006) MED-100.
   Google Scholar
• TAMEHIRO N, SATO Y, SUZUKI T et al.: Riccardin C: a natural product that functions as a liver X receptor (LXR)α agonist and an LXRβ antagonist. FEBS Lett. (2005) 579(24):5299-5304.
   PubMed Web of Science ®Google Scholar
• WATANABE Y, JIANG S, TAKABE W et al.: Expression of LXRα protein in human atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. (2005) 25(3):622-627.
   PubMedGoogle Scholar
• QUINET EM, SAVIO DA, HALPERN AR et al.: LXRβ regulation in LXRα deficient mice: implications for therapeutic targetting. Mol. Pharmacol. (2006).
   PubMedGoogle Scholar
• ALBERS M, BLUME B, SCHLUETER T et al.: A novel principle for partial agonism of liver X receptor ligands. J.Biol. Chem. (2006) 281(8):4920-4930.
   PubMedGoogle Scholar