Main groups of proprotein convertase subtilisin/kexin type 9 inhibitors: mechanisms of action and clinical efficacy. Part 1

DOI: https://doi.org/10.29296/25877305-2021-03-04
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Issue: 
3
Year: 
2021

A. Chaulin(1, 2), N. Svechkov(1, 2), S. Volkova(1) (1)Samara Regional Cardiology Dispensary,
Samara (2)Samara State Medical University

Since establishing the important role of cholesterol and low-density lipoproteins (LDL) in the pathogenesis of atherosclerosis and cardiovascular diseases, many researchers have focused on developing drugs that lower the levels of atherogenic lipoproteins. Thanks to the work of Japanese researcher Akira Endo, the first effective anti-atherosclerotic drugs – statins-were created in the 1970s and 80s. The mechanism of hypocholesterolemic action of statins is based on competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) – reductase, which is necessary for cholesterol biosynthesis. In 2003, a new enzyme, proprotein convertase subtilisin – Kexin type 9 (PCSK9), was discovered and a new mechanism for regulating LDL levels in blood serum. As a result of research, the PCSK9 enzyme has been considered as a target for therapeutic effects to reduce cholesterol and LDL levels. To date, several groups of drugs that inhibit PCSK9 have been developed. In this article, we will review the mechanisms of action and clinical efficacy of the main groups of PCSK9 inhibitors. The first part of the article is devoted to preparations of the group of monoclonal antibodies against PCSK9, antisense oligonucleotides, and small interfering ribonucleic acids.
Keywords: 
cardiology
proprotein convertase subtilisin-Kexin type 9
atherosclerosis
cholesterol
low-density lipoproteins
low-density lipoprotein receptors
cardiovascular diseases
PCSK9 inhibitors
monoclonal antibodies
antisense nucleotides
small interfering ribonucleic acids

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