A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro

The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to ev...

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Autores principales: Li, Li, Shen, Chen, Huang, Ya-Xuan, Li, Ya-Nan, Liu, Xiu-Feng, Liu, Xu-Ming, Liu, Ji-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225438/
https://www.ncbi.nlm.nih.gov/pubmed/30235833
http://dx.doi.org/10.3390/molecules23092397
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author Li, Li
Shen, Chen
Huang, Ya-Xuan
Li, Ya-Nan
Liu, Xiu-Feng
Liu, Xu-Ming
Liu, Ji-Hua
author_facet Li, Li
Shen, Chen
Huang, Ya-Xuan
Li, Ya-Nan
Liu, Xiu-Feng
Liu, Xu-Ming
Liu, Ji-Hua
author_sort Li, Li
collection PubMed
description The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to evaluate potent natural inhibitors preventing the interaction of PCSK9/LDLR directly. Herein, natural compounds with efficacy in the treatment of hypercholesterolemia were chosen to investigate their inhibitory activities on the PCSK9/LDLR interaction. Two of them, polydatin (1) and tetrahydroxydiphenylethylene-2-O-glucoside (2), were identified as potential inhibitors for the PCSK9/LDLR interaction and were proven to prevent PCSK9-mediated LDLR degradation in HepG2 cells. The results suggested that this strategy could be applied for evaluating potential bioactive compounds inhibiting the interaction of PCSK9/LDLR and this strategy could accelerate the discovery of new drug candidates for the treatment of PCSK9-mediated hypercholesterolemia.
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spelling pubmed-62254382018-11-13 A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro Li, Li Shen, Chen Huang, Ya-Xuan Li, Ya-Nan Liu, Xiu-Feng Liu, Xu-Ming Liu, Ji-Hua Molecules Article The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to evaluate potent natural inhibitors preventing the interaction of PCSK9/LDLR directly. Herein, natural compounds with efficacy in the treatment of hypercholesterolemia were chosen to investigate their inhibitory activities on the PCSK9/LDLR interaction. Two of them, polydatin (1) and tetrahydroxydiphenylethylene-2-O-glucoside (2), were identified as potential inhibitors for the PCSK9/LDLR interaction and were proven to prevent PCSK9-mediated LDLR degradation in HepG2 cells. The results suggested that this strategy could be applied for evaluating potential bioactive compounds inhibiting the interaction of PCSK9/LDLR and this strategy could accelerate the discovery of new drug candidates for the treatment of PCSK9-mediated hypercholesterolemia. MDPI 2018-09-19 /pmc/articles/PMC6225438/ /pubmed/30235833 http://dx.doi.org/10.3390/molecules23092397 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Li
Shen, Chen
Huang, Ya-Xuan
Li, Ya-Nan
Liu, Xiu-Feng
Liu, Xu-Ming
Liu, Ji-Hua
A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
title A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
title_full A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
title_fullStr A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
title_full_unstemmed A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
title_short A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR Interaction In Vitro
title_sort new strategy for rapidly screening natural inhibitors targeting the pcsk9/ldlr interaction in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225438/
https://www.ncbi.nlm.nih.gov/pubmed/30235833
http://dx.doi.org/10.3390/molecules23092397
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