标题：PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDL-Cholesterol
作者：Wang, Yan; Liu, Zhao-Peng
作者机构：[Wang, Yan; Liu, Zhao-Peng] Shandong Univ, Sch Pharmaceut Sci, Key Lab Chem Biol, Inst Med Chem,Minist Educ, Jinan 250012, Shandong, Peoples R China.
通讯作者地址：[Liu, ZP]Shandong Univ, Sch Pharmaceut Sci, Key Lab Chem Biol, Inst Med Chem,Minist Educ, Jinan 250012, Shandong, Peoples R China.
来源：MINI-REVIEWS IN MEDICINAL CHEMISTRY
关键词：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
摘要：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-of-function 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.