2023年12月20日 · 如今 默沙东 （Merck & Co.）研发的小分子环肽化药MK-0616，有望成为首款口服PSCK9抑制剂。MK-0616是一种大环多肽分子，可以抑制PCSK9与低密度脂蛋白受体之间的相互作用，从而让更多的LDLR可以回到细胞表面。

口服MK-0616 是一种合成的三环肽，它以与单克隆抗体相似的亲和力，去结合PCSK9和LDL受体之间PPI（蛋白质-蛋白质作用）的扁平界面，从而抑制PCSK9结合LDL受体。所以从本质上说，MK-0616是一种通过影响蛋白质-蛋白质作用（PPI）为机制的PCSK9抑制剂。MK-0616有助于解放 ...

2023年4月28日 · mk-0616 由默克公司发现和开发，是一种在研的、可能是首个口服 pcsk9 抑制剂，旨在降低低密度脂蛋白 (ldl) 胆固醇。 MK-0616 是一种大环肽，可结合 PCSK9 并抑制 PCSK9 与 LDL 受体的相互作用，旨在通过抑制PCSK9可增加LDL-C在血液中的清除。

2023年5月1日 · Results: MK-0616 displayed high affinity (K i = 5pM) for PCSK9 in vitro and sufficient safety and oral bioavailability preclinically to enable advancement into the clinic. In Phase 1 clinical studies in healthy adults, single oral doses of MK-0616 were associated with >93% geometric mean reduction (95% CI, 84-103) of free, unbound plasma PCSK9 ...

2023年3月6日 · mk-0616是基于msd大环多肽 技术平台 开发的 口服pcsk9抑制剂 ，该平台通过mrna展示技术发现能够抑制蛋白之间相互作用的抑制剂。 MK-0616能阻断 PCSK9蛋白 和LDLR的结合，进而降低患者的LDL-C水平。

2023年3月6日 · Discovered and developed by Merck, MK-0616 is an investigational, potentially first oral PCSK9 inhibitor designed to lower low density lipoprotein (LDL) cholesterol. MK-0616 is a macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors. About Hypercholesterolemia

2023年8月25日 · MK-0616 is an investigational, potentially first oral PCSK9 inhibitor designed to lower LDL cholesterol via the same biological mechanism as currently approved injectable PCSK9 inhibitors but in a daily pill form. MK-0616 is a macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors. About ...

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 …

Oral inhibition of PCSK9 with MK-0616 at doses from 6 mg to 30 mg daily provided clinically meaningful reductions of LDL-C that were superior to placebo in participants with hypercholesterolemia with a wide range of ASCVD risks and background statin therapies.

2023年4月25日 · MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from baseline and was well tolerated during 8 weeks of treatment and an additional 8 weeks of follow-up.