Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition

Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to...
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Autor*in:	Dongyan Feng [verfasserIn] Le Ren [verfasserIn] Jiaqi Wu [verfasserIn] Lingling Guo [verfasserIn] Zhitao Han [verfasserIn] Jingjing Yang [verfasserIn] Wei Xie [verfasserIn] Yanbing Wang [verfasserIn] Fanxing Xu [verfasserIn] Xin Su [verfasserIn] Dahong Li [verfasserIn] Hao Cao [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	furin inhibitor pyrethrin I permethrin non-competitive inhibitor allosteric inhibitor

Übergeordnetes Werk:	In: Molecules - MDPI AG, 2003, 28(2023), 4, p 1883
Übergeordnetes Werk:	volume:28 ; year:2023 ; number:4, p 1883

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/molecules28041883

Katalog-ID:	DOAJ080014240

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allfields	10.3390/molecules28041883 doi (DE-627)DOAJ080014240 (DE-599)DOAJc0fa85bfa4c54b6fbaf93a538eee853c DE-627 ger DE-627 rakwb eng QD241-441 Dongyan Feng verfasserin aut Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by <i<Pyrethrum cinerariifolium</i< Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2. furin inhibitor pyrethrin I permethrin non-competitive inhibitor allosteric inhibitor Organic chemistry Le Ren verfasserin aut Jiaqi Wu verfasserin aut Lingling Guo verfasserin aut Zhitao Han verfasserin aut Jingjing Yang verfasserin aut Wei Xie verfasserin aut Yanbing Wang verfasserin aut Fanxing Xu verfasserin aut Xin Su verfasserin aut Dahong Li verfasserin aut Hao Cao verfasserin aut In Molecules MDPI AG, 2003 28(2023), 4, p 1883 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:28 year:2023 number:4, p 1883 https://doi.org/10.3390/molecules28041883 kostenfrei https://doaj.org/article/c0fa85bfa4c54b6fbaf93a538eee853c kostenfrei https://www.mdpi.com/1420-3049/28/4/1883 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 28 2023 4, p 1883
spelling	10.3390/molecules28041883 doi (DE-627)DOAJ080014240 (DE-599)DOAJc0fa85bfa4c54b6fbaf93a538eee853c DE-627 ger DE-627 rakwb eng QD241-441 Dongyan Feng verfasserin aut Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by <i<Pyrethrum cinerariifolium</i< Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2. furin inhibitor pyrethrin I permethrin non-competitive inhibitor allosteric inhibitor Organic chemistry Le Ren verfasserin aut Jiaqi Wu verfasserin aut Lingling Guo verfasserin aut Zhitao Han verfasserin aut Jingjing Yang verfasserin aut Wei Xie verfasserin aut Yanbing Wang verfasserin aut Fanxing Xu verfasserin aut Xin Su verfasserin aut Dahong Li verfasserin aut Hao Cao verfasserin aut In Molecules MDPI AG, 2003 28(2023), 4, p 1883 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:28 year:2023 number:4, p 1883 https://doi.org/10.3390/molecules28041883 kostenfrei https://doaj.org/article/c0fa85bfa4c54b6fbaf93a538eee853c kostenfrei https://www.mdpi.com/1420-3049/28/4/1883 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 28 2023 4, p 1883
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allfieldsSound	10.3390/molecules28041883 doi (DE-627)DOAJ080014240 (DE-599)DOAJc0fa85bfa4c54b6fbaf93a538eee853c DE-627 ger DE-627 rakwb eng QD241-441 Dongyan Feng verfasserin aut Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by <i<Pyrethrum cinerariifolium</i< Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2. furin inhibitor pyrethrin I permethrin non-competitive inhibitor allosteric inhibitor Organic chemistry Le Ren verfasserin aut Jiaqi Wu verfasserin aut Lingling Guo verfasserin aut Zhitao Han verfasserin aut Jingjing Yang verfasserin aut Wei Xie verfasserin aut Yanbing Wang verfasserin aut Fanxing Xu verfasserin aut Xin Su verfasserin aut Dahong Li verfasserin aut Hao Cao verfasserin aut In Molecules MDPI AG, 2003 28(2023), 4, p 1883 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:28 year:2023 number:4, p 1883 https://doi.org/10.3390/molecules28041883 kostenfrei https://doaj.org/article/c0fa85bfa4c54b6fbaf93a538eee853c kostenfrei https://www.mdpi.com/1420-3049/28/4/1883 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 28 2023 4, p 1883
language	English
source	In Molecules 28(2023), 4, p 1883 volume:28 year:2023 number:4, p 1883
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topic_facet	furin inhibitor pyrethrin I permethrin non-competitive inhibitor allosteric inhibitor Organic chemistry
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container_title	Molecules
authorswithroles_txt_mv	Dongyan Feng @@aut@@ Le Ren @@aut@@ Jiaqi Wu @@aut@@ Lingling Guo @@aut@@ Zhitao Han @@aut@@ Jingjing Yang @@aut@@ Wei Xie @@aut@@ Yanbing Wang @@aut@@ Fanxing Xu @@aut@@ Xin Su @@aut@@ Dahong Li @@aut@@ Hao Cao @@aut@@
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callnumber-first	Q - Science
author	Dongyan Feng
spellingShingle	Dongyan Feng misc QD241-441 misc furin inhibitor misc pyrethrin I misc permethrin misc non-competitive inhibitor misc allosteric inhibitor misc Organic chemistry Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition
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topic_title	QD241-441 Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition furin inhibitor pyrethrin I permethrin non-competitive inhibitor allosteric inhibitor
topic	misc QD241-441 misc furin inhibitor misc pyrethrin I misc permethrin misc non-competitive inhibitor misc allosteric inhibitor misc Organic chemistry
topic_unstemmed	misc QD241-441 misc furin inhibitor misc pyrethrin I misc permethrin misc non-competitive inhibitor misc allosteric inhibitor misc Organic chemistry
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title	Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition
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title_full	Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition
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author_browse	Dongyan Feng Le Ren Jiaqi Wu Lingling Guo Zhitao Han Jingjing Yang Wei Xie Yanbing Wang Fanxing Xu Xin Su Dahong Li Hao Cao
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title_sort	permethrin as a potential furin inhibitor through a novel non-competitive allosteric inhibition
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title_auth	Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition
abstract	Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by <i<Pyrethrum cinerariifolium</i< Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2.
abstractGer	Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by <i<Pyrethrum cinerariifolium</i< Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2.
abstract_unstemmed	Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by <i<Pyrethrum cinerariifolium</i< Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2.
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title_short	Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition
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up_date	2024-07-04T01:44:04.667Z
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Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition

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