2021•Proceedings for Annual Meeting of The Japanese Pharmacological SocietyOpen access
Development and functional analysis of novel PCSK9/LDLR interaction inhibitors for hypercholesterolemia treatment
Takumi Yokoyama, Takehiro Ando, Daisuke Fuji, Mizuki Yamamoto, Takashi Kawakami
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Abstract
Hypercholesterolemia characterized by excessively elevated levels of plasma low-density lipoprotein-cholesterol (LDLc) increases the risk of atherosclerosis, causing cardiovascular disease and cerebrovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), which is secreted from liver, interacts with LDL-receptor (LDLR) that uptakes LDLc from plasma into hepatocytes. The PCSK9-LDLR interaction leads degradation of the LDLR on hepatocytes, resulting in elevation of plasma LDLc levels. Although anti-PCSK9 antibodies that inhibit PCSK9-LDLR interaction have been used for the treatment of hypercholesterolemia, the antibody agents are very expensive because they are produced using mammalian cells. To overcome this problem, it is necessary to develop PCSK9/LDLR interaction inhibitors that are produced by chemical synthesis to be low-cost in hypercholesterolemia treatment.
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