PCSK9
耐受性
可欣
载脂蛋白B
医学
前蛋白转化酶
以兹提米比
药理学
家族性高胆固醇血症
胆固醇
药代动力学
内科学
内分泌学
脂蛋白
低密度脂蛋白受体
不利影响
作者
John R. Burnett,Amanda J. Hooper
标识
DOI:10.1080/13543784.2023.2267972
摘要
Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Lowering LDL-cholesterol, by lifestyle modification or therapeutically, reduces the risk of ASCVD. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein which binds to the LDL-receptor and induces degradation, is a clinically validated target to lower LDL-cholesterol. Injectable PCSK9 inhibitor therapies have demonstrated substantial reductions in LDL-cholesterol with associated decreased risk of ASCVD events.MK-0616 is an orally bioavailable, renally excreted, macrocyclic peptide inhibitor of PCSK9. The article provides an understanding of the chemistry and development, pharmacokinetic and pharmacodynamic characteristics of MK-0616 and insight into its clinical efficacy and safety. In clinical trials, MK-0616 produced dose-dependent reductions in LDL-cholesterol, non-HDL-cholesterol, and apolipoprotein (apo) B levels. Furthermore, MK-0616 modestly lowered lipoprotein (a) [Lp(a)].MK-0616 is a potent, oral macrocyclic peptide inhibitor of PCSK9 that is not only able to reduce LDL-cholesterol, non-HDL-cholesterol, and apoB, but can also lower Lp(a). Safety and tolerability studies reported to date are promising. MK-0616 may offer advantages over injectable anti-PCSK9 therapies in terms of ease of dosing, patient preference and cost. The results from phase III trials of MK-0616 on cardiovascular outcomes are awaited with interest.
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