PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol
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Published:2018-12-06
Issue:2
Volume:19
Page:165-176
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ISSN:1389-5575
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Container-title:Mini-Reviews in Medicinal Chemistry
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language:en
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Short-container-title:MRMC
Affiliation:
1. Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
Abstract
Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol
(LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular
disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase
subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its
degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-offunction
mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become
novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors
have been under investigation, and much progress has been made in clinical trials, especially for
monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In
this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides
(ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and
adnectins, and the related safety issues.
Funder
Key Research and Development Program of Shandong province
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology,General Medicine
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