PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol.
Animals
Antibodies, Monoclonal
/ adverse effects
Antibodies, Monoclonal, Humanized
Anticholesteremic Agents
/ adverse effects
Cardiovascular Diseases
/ drug therapy
Cholesterol, LDL
/ antagonists & inhibitors
Drug Discovery
Enzyme Inhibitors
/ adverse effects
Humans
Hypercholesterolemia
/ drug therapy
PCSK9 Inhibitors
Proprotein Convertase 9
/ metabolism
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9)
alirocmab
cardiovascular disease (CVD)
evolocumab
hypercholesterolemia
low-density lipoprotein cholesterol (LDL-C)
low-density lipoprotein receptor (LDLR).
Journal
Mini reviews in medicinal chemistry
ISSN: 1875-5607
Titre abrégé: Mini Rev Med Chem
Pays: Netherlands
ID NLM: 101094212
Informations de publication
Date de publication:
2019
2019
Historique:
received:
26
07
2017
revised:
17
11
2017
accepted:
29
12
2017
pubmed:
26
4
2018
medline:
17
1
2019
entrez:
26
4
2018
Statut:
ppublish
Résumé
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-offunction 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.
Identifiants
pubmed: 29692249
pii: MRMC-EPUB-89908
doi: 10.2174/1389557518666180423111442
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
Anticholesteremic Agents
0
Cholesterol, LDL
0
Enzyme Inhibitors
0
PCSK9 Inhibitors
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
evolocumab
LKC0U3A8NJ
alirocumab
PP0SHH6V16
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
165-176Informations de copyright
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