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Autor
Bartoňková, Iveta 1 Beck, Amanda 1 Brtko, Julius 1 Cavalluzzi, Maria M 1 Chandran, Aneesh 1 Chatterjee, Shirshendu 1 Costello, Cait M 1 Cui, Julia Yue 1 Dvořák, Zdeněk 1 Flannigan, Kyle L 1 Gu, Haiwei 1 Hirota, Simon A 1 Jiskrová, Eva 1 Karunaratne, Chamini V 1 Kemp, Jazmin S 1 Kopp, Felix 1 Kortagere, Sandhya 1 Lentini, Giovanni 1 Li, Hao 1 Mani, Sridhar 1
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Pracoviště
Center for Metabolic and Vascular Bio... 1 Cincinnati Children's Hospital Medica... 1 City University of New York City Coll... 1 Department of Biochemistry Albert Ein... 1 Department of Cell Biology and Geneti... 1 Department of Chemistry City Universi... 1 Department of Chemistry University of... 1 Department of Environmental and Occup... 1 Department of Medicine Genetics and M... 1 Department of Microbiology and Immuno... 1 Department of Pathology Albert Einste... 1 Department of Pediatrics and Immunolo... 1 Department of Pharmaceutical Sciences... 1 Department of Pharmacy Pharmaceutical... 1 Department of Physiology and Pharmaco... 1 Department of Veterinary and Biomedic... 1 Division of Gastroenterology and Hepa... 1 Institute of Experimental Endocrinolo... 1 Molecular Biophysics Unit Indian Inst... 1 The Department of Biological and Envi... 1
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Autor
Bartoňková, Iveta 1 Beck, Amanda 1 Brtko, Julius 1 Cavalluzzi, Maria M 1 Chandran, Aneesh 1 Chatterjee, Shirshendu 1 Costello, Cait M 1 Cui, Julia Yue 1 Dvořák, Zdeněk 1 Flannigan, Kyle L 1 Gu, Haiwei 1 Hirota, Simon A 1 Jiskrová, Eva 1 Karunaratne, Chamini V 1 Kemp, Jazmin S 1 Kopp, Felix 1 Kortagere, Sandhya 1 Lentini, Giovanni 1 Li, Hao 1 Mani, Sridhar 1
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Pracoviště
Center for Metabolic and Vascular Bio... 1 Cincinnati Children's Hospital Medica... 1 City University of New York City Coll... 1 Department of Biochemistry Albert Ein... 1 Department of Cell Biology and Geneti... 1 Department of Chemistry City Universi... 1 Department of Chemistry University of... 1 Department of Environmental and Occup... 1 Department of Medicine Genetics and M... 1 Department of Microbiology and Immuno... 1 Department of Pathology Albert Einste... 1 Department of Pediatrics and Immunolo... 1 Department of Pharmaceutical Sciences... 1 Department of Pharmacy Pharmaceutical... 1 Department of Physiology and Pharmaco... 1 Department of Veterinary and Biomedic... 1 Division of Gastroenterology and Hepa... 1 Institute of Experimental Endocrinolo... 1 Molecular Biophysics Unit Indian Inst... 1 The Department of Biological and Envi... 1
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NLK
Directory of Open Access Journals
od 2009
Free Medical Journals
od 2009
PubMed Central
od 2009
Europe PubMed Central
od 2009
ProQuest Central
od 2009-04-01
Open Access Digital Library
od 2009-01-01
Open Access Digital Library
od 2009-01-01
Open Access Digital Library
od 2009-01-01
Medline Complete (EBSCOhost)
od 2011-01-01
Health & Medicine (ProQuest)
od 2009-04-01
ROAD: Directory of Open Access Scholarly Resources
od 2008
PubMed
32153125
DOI
10.15252/emmm.201911621
Knihovny.cz E-zdroje
The human PXR (pregnane X receptor), a master regulator of drug metabolism, has essential roles in intestinal homeostasis and abrogating inflammation. Existing PXR ligands have substantial off-target toxicity. Based on prior work that established microbial (indole) metabolites as PXR ligands, we proposed microbial metabolite mimicry as a novel strategy for drug discovery that allows exploiting previously unexplored parts of chemical space. Here, we report functionalized indole derivatives as first-in-class non-cytotoxic PXR agonists as a proof of concept for microbial metabolite mimicry. The lead compound, FKK6 (Felix Kopp Kortagere 6), binds directly to PXR protein in solution, induces PXR-specific target gene expression in cells, human organoids, and mice. FKK6 significantly represses pro-inflammatory cytokine production cells and abrogates inflammation in mice expressing the human PXR gene. The development of FKK6 demonstrates for the first time that microbial metabolite mimicry is a viable strategy for drug discovery and opens the door to underexploited regions of chemical space.
- MeSH
- cytokiny MeSH
- kultivované buňky MeSH
- lidé MeSH
- ligandy MeSH
- molekulární mimikry * MeSH
- myši MeSH
- organoidy MeSH
- pregnanový X receptor chemie MeSH
- střeva MeSH
- zánět MeSH
- zvířata MeSH
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- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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