Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method

Cerebral ischemia (IS) is one of the main cardiovascular diseases threatening life and disability. Like most cardiovascular events, the disease progression of is affects a variety of signaling pathways and changes multiple overexpressed genes in the body. The use of new therapeutic agents to interfe...

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Autores principales:	Xiaojiang Peng, Dao-jin Xue
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine (General) R5-920 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/2f85d91c92144ecf8e8a7be52515683d
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spelling	oai:doaj.org-article:2f85d91c92144ecf8e8a7be52515683d2021-11-29T00:55:35ZPhenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method2040-230910.1155/2021/9999340https://doaj.org/article/2f85d91c92144ecf8e8a7be52515683d2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9999340https://doaj.org/toc/2040-2309Cerebral ischemia (IS) is one of the main cardiovascular diseases threatening life and disability. Like most cardiovascular events, the disease progression of is affects a variety of signaling pathways and changes multiple overexpressed genes in the body. The use of new therapeutic agents to interfere with the disease progression of cardiovascular diseases (such as is) can be achieved by selectively regulating small molecules of the target set of different signal pathways, also known as selective multipharmacology. Phenotypic screening can be an effective method to solve this problem, but the lack of targeted methods for ischemic stroke limits its impact. Here, we aim to identify IS-specific targets by RNA sequencing data with a network-based approach. Molecular docking approach was applied to screen over 210,000 molecules from SPECS compound library. Screening of this enriched library resulted in 605 candidates that led to several potent active hits. The novelty analysis suggested that the structure scaffolds of the compounds were dissimilar to existing IKKB inhibitors, and further biological test result confirmed two identified compounds represented novel IKKB inhibitors. Further, docking exploration with IKKB (PDB id: 4KIK) showed that the three selective compounds were stable inside the binding pocket of IKKB which shared a homology of compound-protein interactions in comparison with the bioactive inhibitor of CHEMBL1762621. Our screening method is expected to produce selective multidrug lead compounds for the development of treatments for complex diseases, such as ischemic stroke.Xiaojiang PengDao-jin XueHindawi LimitedarticleMedicine (General)R5-920Medical technologyR855-855.5ENJournal of Healthcare Engineering, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920 Medical technology R855-855.5
spellingShingle	Medicine (General) R5-920 Medical technology R855-855.5 Xiaojiang Peng Dao-jin Xue Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method
description	Cerebral ischemia (IS) is one of the main cardiovascular diseases threatening life and disability. Like most cardiovascular events, the disease progression of is affects a variety of signaling pathways and changes multiple overexpressed genes in the body. The use of new therapeutic agents to interfere with the disease progression of cardiovascular diseases (such as is) can be achieved by selectively regulating small molecules of the target set of different signal pathways, also known as selective multipharmacology. Phenotypic screening can be an effective method to solve this problem, but the lack of targeted methods for ischemic stroke limits its impact. Here, we aim to identify IS-specific targets by RNA sequencing data with a network-based approach. Molecular docking approach was applied to screen over 210,000 molecules from SPECS compound library. Screening of this enriched library resulted in 605 candidates that led to several potent active hits. The novelty analysis suggested that the structure scaffolds of the compounds were dissimilar to existing IKKB inhibitors, and further biological test result confirmed two identified compounds represented novel IKKB inhibitors. Further, docking exploration with IKKB (PDB id: 4KIK) showed that the three selective compounds were stable inside the binding pocket of IKKB which shared a homology of compound-protein interactions in comparison with the bioactive inhibitor of CHEMBL1762621. Our screening method is expected to produce selective multidrug lead compounds for the development of treatments for complex diseases, such as ischemic stroke.
format	article
author	Xiaojiang Peng Dao-jin Xue
author_facet	Xiaojiang Peng Dao-jin Xue
author_sort	Xiaojiang Peng
title	Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method
title_short	Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method
title_full	Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method
title_fullStr	Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method
title_full_unstemmed	Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method
title_sort	phenotypic screening of molecular docking enriched chemical libraries from targets identified in ischemic stroke genome data by network-based method
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/2f85d91c92144ecf8e8a7be52515683d
work_keys_str_mv	AT xiaojiangpeng phenotypicscreeningofmoleculardockingenrichedchemicallibrariesfromtargetsidentifiedinischemicstrokegenomedatabynetworkbasedmethod AT daojinxue phenotypicscreeningofmoleculardockingenrichedchemicallibrariesfromtargetsidentifiedinischemicstrokegenomedatabynetworkbasedmethod
_version_	1718407759800565760

Phenotypic Screening of Molecular Docking Enriched Chemical Libraries from Targets Identified in Ischemic Stroke Genome Data by Network-Based Method

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