Inhibitors of cholesteryl ester transfer protein - A new approach to coronary artery disease

Expert Opinion on Investigational Drugs

Volumn 15, Issue 2, 2006, Pages 99-106

  Doggrell, Sheila A ^a  

^a AUCKLAND UNIVERSITY OF TECHNOLOGY   (New Zealand)

Author keywords

Antibodies against CETP; Cholesteryl ester protein; Coronary artery disease; HDL cholesterol; JTT 705; LDL cholesterol; Torcetrapib

Indexed keywords

2 METHYLPROPANETHIOIC ACID S [2 [1 (2 ETHYLBUTYL)CYCLOHEXYLCARBOXAMIDO]PHENYL] ESTER; 3 (3 FLUOROPHENYL) 3,4 DIDYDRO 2H 1 BENZOPYRAN 6,7 DIOL; 3 [[3 (4 CHLORO 3 ETHYLPHENOXY)PHENYL][3 (1,1,2,2 TETRAFLUOROETHOXY)BENZYL]AMINO] 1,1,1 TRIFLUOROPROPAN 2 OL; ATORVASTATIN; CGS 25159; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYPOCHOLESTEROLEMIC AGENT; JTP 25203; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PRAVASTATIN; SC 71952; TORCETRAPIB; UNCLASSIFIED DRUG;

CARDIOVASCULAR RISK; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DISEASE ASSOCIATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG STRUCTURE; DYSLIPIDEMIA; ENZYME ACTIVITY; ENZYME INHIBITION; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; MOLECULAR MECHANICS; NONHUMAN; REVIEW;

ANIMALS; ANTICHOLESTEREMIC AGENTS; CARRIER PROTEINS; CHOLESTEROL ESTER TRANSFER PROTEINS; CORONARY ARTERIOSCLEROSIS; DRUGS, INVESTIGATIONAL; GLYCOPROTEINS; HUMANS;

EID: 32844469288     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.15.2.99     Document Type: Review

References (46)

1. DOGGRELL SA: Statins in the 21st century: end of the simple story? Expert Opin. Investig. Drugs (2001) 10:1755-1766.
2. GENEST JJ, McNAMARA JR, SALEM DN, SCHAEFER EJ: Prevalence of risk factors in men with premature coronary artery disease. Am. J. Cardiol. (1991) 67:1185-1189.
3. GORDON DJ, PROBSTFIELD JL, GARRISON RJ et al.: High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation (1989) 79:8-15.
4. LINSEL-NITSCHKE P, TALL AR: HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat. Rev. Drug Discov. (2005) 4:193-205.
5. RUBINS HB, ROBINS SJ, COLLINS D et al.: 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. (1999) 341:410-418.
6. RUBINS HB, DAVENPORT J, BABIKIAN V et al.: Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol. The Veterans Affairs HDL Intervention Trial (VA-HIT). Circulation (2001) 103:2828-2833.
7. DIABETES ATHEROSCLEROSIS INTERVENTION STUDY INVESTIGATORS: Effect of fenofibrate on progression of coronary-artery disease in Type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet (2001) 357:905-910.
8. BARTER PJ, BREWER HB Jr, CHAPMAN MJ et al.: Cholesteryl ester transfer protein - a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler. Thromb. Vasc. Biol. (2003) 23:160-167.
9. OHASHI R, MU H, WANG X, YAO Q, CHEN C: Reverse cholesterol transport and cholesterol efflux in atherosclerosis. QJM (2005) 98(12):845-856.
10. DE VRIES R, KERSTENS MN, SLUITER WJ et al.: Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic Type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment. Diabetologica (2005) 48:1105-1113.
11. DE GROOTH GJ, KLERKX AHEM, STROES ESG et al.: A review of CETP and its relation to atherosclerosis. J. Lipid Res. (2004) 45:1967-1974.
12. INAZU A, BROWN ML, HESLER CB et al.: Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N. Engl. J. Med. (1990) 323:1234-1238.
13. MORIYAMA Y, OKAMURA T, INAZU A et al.: A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency. Prev. Med. (1998) 5:659-667.
14. BOEKHOLDT SM, KUIVENHOVEN JA, WAREHAM NJ et al.: Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women: the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) - Norfolk population study. Circulation (2004) 110:1418-1423.
15. ORDOVAS JM, CUPPLES LA, CORELLA D et al.: Association of the cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler. Thromb. Vasc. Biol. (2000) 20:1323-1329.
16. BROUSSEAU ME, O'CONNOR JJ, ORDOVAS JM et al.: Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler. Thromb. Vasc. Biol. (2002) 22:1148-1154.
17. FREEMAN DJ, SAMANI NJ, WILSON V et al.: A polymorphism of the cholesteryl ester protein gene predicts cardiovascular events in non-smokers in the West of Scotland Coronary Prevention Study. Eur. Heart J. (2003) 24:1833-1842.
18. KLERKX AH, DE GROOTH GJ, ZWINDERMAN AH et al.: Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS). Eur. J. Clin. Invest. (2004) 34:21-28.
19. DE GROOTH GJ, ZERBA KE, HUANG SP et al.: The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effect on cardiovascular outcome: a prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy. J. Am. Coll. Cardiol. (2004) 43:854-857.
20. BLANKENBERG S, RUPPRECHT HJ, BICKEL C et al.: Common genetic variation of the cholesteryl ester transfer protein gene strongly predicts future cardiovascular death in patients with coronary artery disease. J. Am. Coll. Cardiol. (2003) 41:1983-1989.
21. RELVAS WG, IZAR MC, HELFENSTEIN T et al.: Relationship between gene polymorphisms and prevalence of myocardial infarction among diabetic and non-diabetic subjects. Atherosclerosis (2005) 178:101-105.
22. BOEKHOLDT SM, SACKS FM, JUKEMA JW et al.: Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation (2005) 111:278-287.
23. SODERLUND S, SORO-PAAVONEN A, EHNHOLM C, JAUHIAINEN M, TASKINEN MR: Hypertriglyceridemia is associated with preβ-HDL levels in subjects with familial low HDL. J. Lipid Res. (2005) 46:1643-1651.
24. SUGANO M, MAKINO N, SAWADA S et al.: Effect of antisense oligonucleotides against cholesteryl ester transfer proteins on the development of atherosclerosis in cholesterol-fed rabbits. J. Biol. Chem. (1998) 273:5033-5036.
25. RITTERSHAUS CW, MILLER DP, THOMAS LJ et al.: Vaccine-induced antibodies inhibit CETP activity in vivo and aortic lesions in a rabbit model of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. (2000) 20:2106-2112.
26. GAOFU Q, JUN L, XIN Y et al.: Vaccinating rabbits with a cholesteryl ester transfer protein (CETP) B-cell epitope carried by heat shock protein-65 (HSP65) for inducing anti-CETP antibodies and reducing aortic lesions in vivo. J. Cardiovasc. Pharmacol. (2005) 45:591-598.
27. DAVIDSON MH, MAKI K, UMPOROWICZ D et al.: The safety and immunogenicity of a CETP vaccine in healthy adults. Atherosclerosis (2003) 169:113-120.
28. KOTHARI HV, POIRIER KJ, LEE WH, SATOH Y: Inhibition of cholesteryl ester transfer protein by CGS 25159 and changes in lipoproteins in hamsters. Atherosclerosis (1997) 128:549-566.
29. HOPE HR, HEUVELMAN D, DUFFIN K et al.: Inhibition of cholesteryl ester transfer protein by substituted dithiobisnicotinic acid dimethyl ester: involvement of a critical cysteine. J. Lipid Res. (2000) 41:1604-1614.
30. SHINKAI H, MAEDA K, YAMASAKI T, OKAMOTO H, UCHIDA I: Bis(2-(acylamino)phenyl)disulfides, 2-(acylamino)benzenethiols, and S-(2-acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. J. Med. Chem. (2000) 43:3566-3572.
31. OKAMOTO H, IWAMOTO Y, MAKI M et al.: Effect of JTT-705 on cholesteryl ester transfer protein and plasma lipid levels in normolipidemic animals. Eur. J. Pharmacol. (2003) 466:147-154.
32. OKAMOTO H, YONEMORI F, WAKITANI K et al.: A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature (2000) 46:203-206.
33. HUANG Z, INAZU A, NOHARA A, HIGASHIKATA T, MABUCHI H: Cholesteryl ester protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolemia. Clin. Sci. (Lond). (2002) 103:587-594.
34. SHIMOJI E, ZHANG B, FAN P, SAKU K: Inhibition of cholesteryl ester transfer protein increases serum apolipoprotein (apo) A-I levels by increasing the synthesis of apoA-I in rabbits. Atherosclerosis (2004) 172:247-257.
35. ZHANG B, FAN P, SHIMOJU E et al.: Inhibition of cholesteryl ester transfer protein activity by JTT-705 increases apolipoprotein E-containing high-density lipoprotein and favorably affects the function and enzyme composition of high-density lipoprotein in rabbits. Arterioscler. Thromb. Vasc. Biol. (2004) 24:1910-1915.
36. DE GROOTH GJ, KUIVENHOVEN JA, STALENHOEF AFH et al.: Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans - a randomized Phase II dose-response study. Circulation (2002) 105:2159-2165.
37. KUIVENHOVEN JA, DE GROOTH GJ, KAWAMUARA H et al.: Effectiveness of inhibition of cholesteryl ester transfer protein by JTT-705 in combination with pravastatin in type II dyslipedemia. Am. J. Cardiol. (2005) 95:1085-1088.
38. CLARK RW, SUTFIN TA, RUGGERI RB et al.: Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler. Thromb. Vasc. Biol. (2004) 24:490-497.
39. LLOYD DB, LIRA ME, WOOD LS et al.: Cholesteryl ester transfer protein variants have differential stability but uniform inhibition by torcetrapib. J. Biol. Chem. (2005) 280:14918-14922.
40. BROUSSEAU ME, DIFFENDERFER MR, MILLAR JS et al.: Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler. Thromb. Vasc. Biol. (2005) 25:1057-1064.
41. BROUSSEAU ME, SCHAEFER EJ, WOLFE ML et al.: Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N. Engl. J. Med. (2004) 350:1505-1515.
42. REINHARD EJ, WANG JL, DURLEY RC et al.: Discovery of a simple picomolar inhibitor of cholesteryl ester transfer protein. J. Med. Chem. (2003) 46:2152-2168.
43. MAEDA K, OKAMOTO H, SHINKAR H: S-(2-(acylamino)phenyl) 2,2-dimethylpropanethioates as CETP inhibitors. Bioorg. Med. Chem. Lett. (2004) 14:2589-2591.
44. BRÜCKNER D, HAFNER F-H, LI V et al.: Dibenzodioxocinones - a new class of CETP inhibitors. Bioorg. Med. Chem. Lett. (2005) 15:3611-3614.
45. VAN WIJK JP, BUIRMA R, VAN TOL A et al.: Effects of increasing doses of simvastatin on fasting lipoprotein subfractions, and the effect of high-dose simvastatin on postprandial chylomicron remnant clearance in normotriglyceridemic patients with premature coronary sclerosis. Atherosclerosis (2005) 178:147-155.
46. GOTTO AM Jr: High-density lipoprotein cholesterol and triglycerides as therapeutic targets for preventing and treating coronary artery disease. Am. Heart J. (2002) 144(Suppl. 6):S33-S42.