Discovery and SAR analysis of phenylbenzo[d][1,3]dioxole-based proprotein convertase subtilisin/kexin type 9 inhibitors.
LDL
LDLR
PCSK9
protein-protein interaction
small molecule
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
entrez:
20
7
2022
pubmed:
21
7
2022
medline:
22
7
2022
Statut:
ppublish
Résumé
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapeutic target for the development of cholesterol-lowering drugs. In the discovery of PCSK9/LDLR (low-density lipoprotein receptor) protein-protein interaction (PPI) impairing small molecules, a total of 47 phenylbenzo[d][1,3] dioxole-based compounds were designed and synthesised. The result revealed that the 4-chlorobenzyl substitution in the amino group is important for the PPI disrupting activity. In the hepatocyte-based functional tests, active compounds such as
Identifiants
pubmed: 35854672
doi: 10.1080/14756366.2022.2101645
pmc: PMC9307114
doi:
Substances chimiques
Dioxoles
0
PCSK9 Inhibitors
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Subtilisins
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2017-2035Références
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