In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking

ABSTRACT: Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibito...

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Autores principales: Pu, Yinglan, Liu, Hui, Zhou, Yeheng, Peng, Jiale, Li, Yaping, Li, Penghua, Li, Yingying, Liu, Xingyong, Zhang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2017
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481271/
https://www.ncbi.nlm.nih.gov/pubmed/28577290
http://dx.doi.org/10.1007/s13659-017-0126-x
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author Pu, Yinglan
Liu, Hui
Zhou, Yeheng
Peng, Jiale
Li, Yaping
Li, Penghua
Li, Yingying
Liu, Xingyong
Zhang, Li
author_facet Pu, Yinglan
Liu, Hui
Zhou, Yeheng
Peng, Jiale
Li, Yaping
Li, Penghua
Li, Yingying
Liu, Xingyong
Zhang, Li
author_sort Pu, Yinglan
collection PubMed
description ABSTRACT: Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based (pharmacophore) virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules). The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa, and 10 novel structural compounds were discovered as potent candidate molecules. This work could be helpful in further design and development of FXa inhibitors. GRAPHICAL ABSTRACT: [Image: see text]
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spelling pubmed-54812712017-07-07 In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking Pu, Yinglan Liu, Hui Zhou, Yeheng Peng, Jiale Li, Yaping Li, Penghua Li, Yingying Liu, Xingyong Zhang, Li Nat Prod Bioprospect Original Article ABSTRACT: Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based (pharmacophore) virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules). The binding modes analysis provide insights into the contribution of particular structural moieties of the compounds towards their activity against FXa, and 10 novel structural compounds were discovered as potent candidate molecules. This work could be helpful in further design and development of FXa inhibitors. GRAPHICAL ABSTRACT: [Image: see text] Springer Singapore 2017-06-02 /pmc/articles/PMC5481271/ /pubmed/28577290 http://dx.doi.org/10.1007/s13659-017-0126-x Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Pu, Yinglan
Liu, Hui
Zhou, Yeheng
Peng, Jiale
Li, Yaping
Li, Penghua
Li, Yingying
Liu, Xingyong
Zhang, Li
In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking
title In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking
title_full In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking
title_fullStr In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking
title_full_unstemmed In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking
title_short In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking
title_sort in silico discovery of novel fxa inhibitors by pharmacophore modeling and molecular docking
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481271/
https://www.ncbi.nlm.nih.gov/pubmed/28577290
http://dx.doi.org/10.1007/s13659-017-0126-x
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