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

doi:10.1007/s13659-017-0126-x

应用天然产物 ›› 2017, Vol. 7 ›› Issue (3): 249-256.DOI: 10.1007/s13659-017-0126-x

• Original article • 上一篇下一篇

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

Yinglan Pu, Hui Liu, Yeheng Zhou, Jiale Peng, Yaping Li, Penghua Li, Yingying Li, Xingyong Liu, Li Zhang

School of Chemical Engineering, Sichuan University of Science & Engineering, Zigong, China

收稿日期:2017-03-14 修回日期:2017-04-05 出版日期:2017-06-24 发布日期:2018-02-06
通讯作者: Li Zhang,e-mail:zhangli19700554@163.com
基金资助:
We gratefully thank financial assistance from the Science and Technology Innovation Talent Project of Sichuan province (Grant number 2016073).

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

Yinglan Pu, Hui Liu, Yeheng Zhou, Jiale Peng, Yaping Li, Penghua Li, Yingying Li, Xingyong Liu, Li Zhang

School of Chemical Engineering, Sichuan University of Science & Engineering, Zigong, China

Received:2017-03-14 Revised:2017-04-05 Online:2017-06-24 Published:2018-02-06
Supported by:
We gratefully thank financial assistance from the Science and Technology Innovation Talent Project of Sichuan province (Grant number 2016073).

摘要/Abstract

摘要： 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.

关键词: FXa, Thrombotic diseases, Pharmacophore, 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 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.

Key words: FXa, Thrombotic diseases, Pharmacophore, Docking

Yinglan Pu, Hui Liu, Yeheng Zhou, Jiale Peng, Yaping Li, Penghua Li, Yingying Li, Xingyong Liu, Li Zhang. In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking[J]. 应用天然产物, 2017, 7(3): 249-256.

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

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

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