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Review

Emerging lipid-lowering drugs: squalene synthase inhibitors

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Pages 309-322 | Published online: 08 Jun 2008

Bibliography

  • World Health Organization. Prevention of recurrent heart attacks and strokes in low and middle income populations. Evidence-based recommendations for policy makers and health professionals, 2003. Available from: http://www.who.int/cardiovascular_rdiseases/guidelines/Full%20text.pdf [Last accessed 2 October 2007]
  • MacKay J, Mensah GA. The Atlas of Heart Disease and Stroke. World Health Organization, 2004. Available from: http://www.who.int/cardiovascular_diseases/resources/atlas/en/ [Last accessed 2 October 2007]
  • Liu L. Cardiovascular diseases in China. Bichem Cell Biol 2007;85:157-63
  • Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics – 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. Available from: www.americanheart.org/downloadable/heart/1166712318459HS_StatsInsideText.pdf [Last accessed 6 February 2007]
  • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP Adult Treatment Panel III). JAMA 2001;285:2486-97
  • Evans M, Roberts A, Davies S, et al. Medical lipid regulating therapy: current evidence, ongoing trials and future developments. Drugs 2004;64:1181-96
  • Pearson TA, Laurora I, Chu H, Kafonek S. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid- lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000;160:459-67
  • Davidson MH. Differences between clinical trial efficacy and real-world effectiveness. Am J Manag Care 2006;12(Suppl):S405-11
  • Lindgren P, Borgström F, Stålhammar J, et al. Determinants of cholesterol goal attainment at 12 months in patients with hypercholesterolaemia not at consensus goal after 3 months of treatment with lipid-lowering drugs. Int J Clin Pract 2007;61:1410-4
  • Stein E, Stender S, Mata P, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J 2004;148:447-55
  • Pearson TA, Denke MA, McBride PE, et al. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc 2005;80:587-95
  • Kamal-Bahl SJ, Burke T, Watson D, Wentworth C. Discontinuation of lipid modifying drugs among commercially insured United States patients in recent clinical practice. Am J Cardiol 2007;99:530-4
  • Vaughan C, Gotto A. Update on statins: 2003. Circulation 2004;110:886-92
  • Chong P, Bachenheimer B. Current, new and future treatments in dyslipidaemia and atherosclerosis. Drugs 2000;60:55-63
  • Vermes A, Vermes I. Genetic polymorphisms in cytochrome P450 enzymes: effect on efficacy and tolerability of HMG-CoA reductase inhibitors. Am J Cardiovasc Drugs 2004;4:247-55
  • Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-81
  • Tavridou A, Kaklamanis L, Papalois A, et al. EP2306, a novel squalene synthase inhibitor, reduces atherosclerosis in the cholesterol-fed rabbit. J Pharmacol Exp Ther 2007: published online 5 September 2007;323:794-804
  • Wolfrum S, Jenen K, Liao J. Endothelium-dependent effects of statins. Arterioscler Thromb Vasc Biol 2003;23:729-36
  • Chrysselis M, Rekka E, Siskou I, Kourounakis P. Nitric oxide releasing morpholine derivatives as hypolipidemic and antioxidant agents. J Med Chem 2002;45:5406-9
  • Scharnagl H, Marz W. New lipid-lowering agents acting on LDL receptors. Curr Top Med Chem 2005;5:233-42
  • Biller SA, Neuenschwander K, Ponpipom MM, et al. Squalene Synthase inhibitors. Curr Pharm Des 1996;2:1-40
  • Petras S, Lindsey S, Harwood J. HMG-CoA reductase regulation: use of structurally diverse first half reaction squalene synthetase inhibitors to characterize the site of mevalonate-derived nonsterol regulator production in cultured IM-9 cells. J Lipid Res 1999;40:24-38
  • Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;375:1301-10
  • Athyros VG, Kakafika AI, Papageorgiou AA, et al. Atorvastatin decreases triacylglycerol-associated risk of vascular events in coronary heart disease patients. Lipids 2007;42:999-1009
  • Chan C, Andreotti D, Cox B, et al. The squalestatins: decarboxy and 4-deoxy analogues as potent squalene synthase inhibitors. J Med Chem 1998;39:207-16
  • Ugawa T, Kakuta H, Moritani H, et al. Experimental model of escape phenomenon in hamsters and the effectiveness of YM-53601 in the model. Br J Pharmacol 2002;135:1572-8
  • Bergstorm J, Kurtz M, Rew D, et al. Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. Proc Natl Acad Sci USA 1993;90:80-4
  • Hiyoshi H, Yanagimachi M, Ito M, et al. Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes. J Lipid Res 2003;44:128-35
  • Bergstorm JD, Dufresne C, Bills GF, et al. Discovery, biosynthesis, and mechanism of action of the zaragozic acids: potent inhibitors of squalene synthase. Ann Rev Microbiol 1995;49:607-39
  • Procopiou PA, Bailey EJ, Bamford MJ, et al. The squalestatins: novel inhibitors of squalene synthase. Enzyme Inhibitory activities and in vivo evaluation of C1-modified analogues. J Med Chem 1994;37:3274-81
  • Nakamura S. Total synthesis of the squalene synthase inhibitor zaragozic acid C. Chem Pharm Bull (Tokyo) 2005;53:1-10
  • Wierzbicki AS. New lipid-lowering agents. Expert Opin Emerging Drugs 2003;8:365-76
  • Magnin DR, Biller SA, Chen Y, et al. α-phosphonosulfonic acids: potent and selective inhibitors of squalene synthase. J Med Chem 1996;39:657-60
  • Tvridou A, Kaklamanis L, Megaritis G, et al. Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Eur J Pharmacol 2006;535:34-42
  • Drug summary information on quinine and quinidine. Micromedex Healthcare Series. Available from: http://www.thomsonhc.com/home/dispatch [Last accessed 25 November 2007]
  • Chrysselis M, Rekka E, Kourounakis P. Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity. J Med Chem 2000;43:609-12
  • Tavridou A, Manolopoulos V. Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo. Eur J Pharmacol 2004;505:213-21
  • Tavridou A, Megaritis G, Kourounakis A, et al. EP2306 and EP2302, two novel squalene synthase inhibitors, stimulate endothelial nitric oxide synthase expression in cultured endothelial cells. Endothelium 2007;14:239-43
  • Miki T, Kori M, Tozawa R, et al. Syntheses of (4-1-benzoxzepine-3-ylidene) acetic acid derivatives and their inhibition of squalene synthase. Chem Pharm Bull (Tokyo) 2002;50:53-8
  • Nishimoto T, Amano Y, Tozawa R. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br J Pharmacol 2003;139:911-8
  • Burnett JR. Drug evaluation: TAK-475 – an oral inhibitor of squalene synthase for hyperlipidemia. Curr Opin Investig Drugs 2006;7:850-6
  • Miki T, Kori M, Mabuchi H, et al. Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis. J Med Chem 2002;45:4571-80
  • Brookes L. Lowering LDL cholesterol: beyond statins. American Heart Association 2006 scientific sessions: Newer approaches to treating dyslipidemia. CME. Medscape, 2006. Available from: http://www.medscape.com/viewarticle/551353 [Last accessed 10 November 2007]
  • Masashi S. Inhibition of squalene synthase is effective in stabilization of coronary plaques [abstract]. J Clin Lipidol 2007;1:341
  • Lilly SM, Rader DJ. New targets and emerging therapies for reducing LDL cholesterol. Curr Opin Lipidol 2007;18:650-5
  • Kalinowski L, Dobrucki IT, Malinski T. Cerivastatin potentiates nitric oxide release and eNOS expression through inhibition of isoprenoids synthesis. J Physiol Pharmacol 2002;53:585-95
  • Jantzen F, Könemann S, Wolff B, et al. Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells. J Physiol Pharmacol 2007;58:503-14
  • Bedi M, Niesen M, Lopez D. Inhibition of squalene synthase upregulates PCSK9 expression in rat liver. Arch Biochem Biophys 2008;470:116-9
  • Nishimoto T, Tozawa R, Amano Y, et al. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in human myocytes. Biochem Pharmacol 2003;66:2133-9
  • Nishimoto T, Eliichiro I, Anayama H, et al. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs. Toxicol Appl Pharmacol 2007;223:39-45
  • Tanaka M, et al. Use of Tak-475 together with ezetimibe for treating hyperlipidemia. WO058335; 2007
  • Takeda provides update on development status of TAK-475, an investigational compound for treatment of hypercholesterolemia. Takeda Pharmaceutical Company Limited, 2007. Available from: http://www.takeda.com/press/article_28386.html [Last accessed 22 November 2007]
  • Piper E, Price G, Chen Y. TAK-475, a squalene synthase inhibitor improves lipid profile in hyperlipidemic subjects [abstract 1493]. Circulation 2006;114(Suppl):288
  • Perez A, Kupfer S, Chen Y. Addition of TAK-475 to atorvastatin provides incremental lipid benefits [abstract 675]. Circulation 2006;114(Suppl):113
  • Bays HE, Weiss RJ, Rhyne JM, et al. Lapaqistat acetate monotherapy: effects of a novel squalene synthase inhibitor on LDL-C levels and other lipid parameters in patients with primary hypercholesterolemia [abstract 682]. Circulation 2007;116(Suppl):127
  • Davidson MH, Brookes L. The ongoing search to lower LDL-cholesterol: targeting squalene synthase CME. Medscape, 2007. Available from: http://www.medscape.com/viewarticle/567893 [Last accessed 2 February 2008]
  • Davidson MH, Maki KC, Zavoral JH, et al. Lapaquistat acetate, a novel squalene synthase inhibitor, co-administered with atorvastatin reduces plasma lipids and C-reactive protein levels in subjects with primary hypercholesterolemia [abstract 193]. Circulation 2007;116(Suppl):17
  • Studies on lapaquistat. Available from: http://www.clinicaltrials.gov/ [Last accessed 2 January 2008]
  • Discontinuation of development of TAK-475, a compound for treatment of hypercholesterolemia. Takeda Pharmaceutical Company Limited, 2008. Available from: http://www.takeda.com/press/article_29153.html [Last accessed 29 April 2008]
  • Matsumoto T. Preventive therapeutic agent for respiratory disease. WO032696; 2008
  • Young JM, Florkowski CM, Molyneux SL, et al. Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. Am J Cardiol 2007;100:1400-3
  • Caso G, Kelly P, McNurlan MA, et al. Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. Am J Cardiol 2007;99:1409-12
  • Studies on ubiquinone or coenzyme Q10. Available from: http://www.clinicaltrials.gov/ [Last accessed 24 March 2008]
  • Pepe S, Marasco SF, Haas SJ, et al. Coenzyme Q10 in cardiovascular disease. Mitochondrion 2007;7:S154-67
  • Drug summary information on ubiquinone or coenzyme Q10. Micromedex Healthcare Series. Available from: http://www.thomsonhc.com/home/dispatch [Last accessed 24 March 2008]
  • Adis International Ltd. Individualisation of treatment regimens and goals is recommended for managing familial dyslipidaemias. Drugs Ther Perspect 2007;23:12-9
  • Okazaki H, Tazoe F, Okazaki S, et al. Increased cholesterol biosynthesis and hypercholesterolemia in mice overexpressing squalene synthase in the liver. J Lipid Res 2006;47:1950-8
  • Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109-22
  • Tenenbaum A, Fisman EZ, Motro M, et al. Optimal management of combined dyslipidemia: what have we behind statins monotherapy? Adv Cardiol 2008;45:127-53
  • Charlton-Menys V, Durrington P. Squalene synthase inhibitors: clinical pharmacology and cholesterol lowering potential. Drugs 2007;67:11-6

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