Submit Manuscript  

Article Details


PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol

[ Vol. 19 , Issue. 2 ]

Author(s):

Yan Wang and Zhao-Peng Liu*   Pages 165 - 176 ( 12 )

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.

Keywords:

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9), low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein receptor (LDLR), cardiovascular disease (CVD), hypercholesterolemia, alirocmab, evolocumab.

Affiliation:

Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012

Graphical Abstract:



Read Full-Text article