Novel therapeutic agents for lowering low density lipoprotein cholesterol

被引：23

作者：

Joy, Tisha R. ^{[1
]}

机构：

[1] Univ Western Ontario, Schulich Sch Med & Dent, London, ON N6A 5K8, Canada

来源：

PHARMACOLOGY & THERAPEUTICS | 2012年 / 135卷 / 01期

关键词：

Anti-sense oligonucleotides; Apolipoprotein B; PCSK9; inhibitor; Thyromimetics; MTP inhibitor; TRIGLYCERIDE TRANSFER PROTEIN; INTESTINE-SPECIFIC INHIBITOR; HORMONE RECEPTOR-BETA; APOLIPOPROTEIN-B; LDL CHOLESTEROL; ANTISENSE OLIGONUCLEOTIDE; PLASMA-CHOLESTEROL; MTP INHIBITOR; SERUM-CHOLESTEROL; L-THYROXINE;

D O I：

10.1016/j.pharmthera.2012.03.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated with an increased risk for cardiovascular disease (CVD). Despite a 25-30% reduction in CVD risk with LDL-C reducing strategies, there is still a significant residual risk. Moreover, achieving target LDL-C values in individuals at high CVD risk is sometimes limited because of tolerability and/or efficacy. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight some of these therapeutic agents including anti-sense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, microsomal triglyceride transfer protein inhibitors, and thyromimetics. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：31 / 43

页数：13

共 83 条

[1] Mutations in PCSK9 cause autosomal dominant hypercholesterolemia [J].

Abifadel, M ;

Varret, M ;

Rabès, JP ;

Allard, D ;

Ouguerram, K ;

Devillers, M ;

Cruaud, C ;

Benjannet, S ;

Wickham, L ;

Erlich, D ;

Derré, A ;

Villéger, L ;

Farnier, M ;

Beucler, I ;

Bruckert, E ;

Chambaz, J ;

Chanu, B ;

Lecerf, JM ;

Luc, G ;

Moulin, P ;

Weissenbach, J ;

Prat, A ;

Krempf, M ;

Junien, C ;

Seidah, NG ;

Boileau, C .

NATURE GENETICS, 2003, 34 (02) :154-156

[2]

Aegerion Pharmaceuticals Inc, 2011, Q REP

[3] JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs [J].

Aggarwal D. ;

West K.L. ;

Zern T.L. ;

Shrestha S. ;

Vergara-Jimenez M. ;

Fernandez M.L. .

BMC Cardiovascular Disorders, 5 (1)

[4] Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia [J].

Akdim, Fatima ;

Tribble, Diane L. ;

Flaim, JoAnn D. ;

Yu, Rosie ;

Su, John ;

Geary, Richard S. ;

Baker, Brenda F. ;

Fuhr, Rainard ;

Wedel, Mark K. ;

Kastelein, John J. P. .

EUROPEAN HEART JOURNAL, 2011, 32 (21) :2650-2659

[5] Effect of Mipomersen, an Apolipoprotein B Synthesis Inhibitor, on Low-Density Lipoprotein Cholesterol in Patients With Familial Hypercholesterolemia [J].

Akdim, Fatima ;

Visser, Maartje E. ;

Tribble, Diane L. ;

Baker, Brenda F. ;

Stroes, Erik S. G. ;

Yu, Rosie ;

Flaim, Joann D. ;

Su, John ;

Stein, Evan A. ;

Kastelein, John J. P. .

AMERICAN JOURNAL OF CARDIOLOGY, 2010, 105 (10) :1413-1419

[6] Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy [J].

Akdim, Fatima ;

Stroes, Erik S. G. ;

Sijbrands, Eric J. G. ;

Tribble, Diane L. ;

Trip, Mieke D. ;

Jukema, J. Wouter ;

Flaim, JoAnn D. ;

Su, John ;

Yu, Rosie ;

Baker, Brenda F. ;

Wedel, Mark K. ;

Kastelein, John J. P. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 55 (15) :1611-1618

[7]

Alnylam Pharmaceuticals, 2012, ALN REP POS PREL CLI

[8]

[Anonymous], 1972, Jama-Journal of the American Medical Association, V220, P996, DOI DOI 10.1001/JAMA.1972.03200070084015

[9]

[Anonymous], 2011, SAFETY STUDY BMS 844

[10]

[Anonymous], A Multiple Ascending Dose Phase I Study of SB 9200 in Treatment Naive Adults With Chronic Hepatitis C Infection

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