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N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy

The characterization of microbiota mechanisms in health and disease has reinvigorated pattern recognition receptors as prominent targets for immunotherapy. Notably, our recent studies on Enterococcus species revealed peptidoglycan remodeling and activation of NOD2 as key mechanisms for microbiota en...

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Detalles Bibliográficos
Autores principales: Griffin, Matthew E., Tsukidate, Taku, Hang, Howard C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901186/
https://www.ncbi.nlm.nih.gov/pubmed/36747725
http://dx.doi.org/10.1101/2023.01.26.525573
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author Griffin, Matthew E.
Tsukidate, Taku
Hang, Howard C.
author_facet Griffin, Matthew E.
Tsukidate, Taku
Hang, Howard C.
author_sort Griffin, Matthew E.
collection PubMed
description The characterization of microbiota mechanisms in health and disease has reinvigorated pattern recognition receptors as prominent targets for immunotherapy. Notably, our recent studies on Enterococcus species revealed peptidoglycan remodeling and activation of NOD2 as key mechanisms for microbiota enhancement of immune checkpoint inhibitor therapy. Inspired by this work and other studies of NOD2 activation, we performed in silico ligand screening and developed N-arylpyrazole dipeptides as novel NOD2 agonists. Importantly, our N-arylpyrazole NOD2 agonist is enantiomer-specific, effective at promoting immune checkpoint inhibitor therapy and requires NOD2 for activity in vivo. Given the significant functions of NOD2 in innate and adaptive immunity, these next-generation agonists afford new therapeutic leads and adjuvants for a variety of NOD2-responsive diseases.
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spelling pubmed-99011862023-02-07 N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy Griffin, Matthew E. Tsukidate, Taku Hang, Howard C. bioRxiv Article The characterization of microbiota mechanisms in health and disease has reinvigorated pattern recognition receptors as prominent targets for immunotherapy. Notably, our recent studies on Enterococcus species revealed peptidoglycan remodeling and activation of NOD2 as key mechanisms for microbiota enhancement of immune checkpoint inhibitor therapy. Inspired by this work and other studies of NOD2 activation, we performed in silico ligand screening and developed N-arylpyrazole dipeptides as novel NOD2 agonists. Importantly, our N-arylpyrazole NOD2 agonist is enantiomer-specific, effective at promoting immune checkpoint inhibitor therapy and requires NOD2 for activity in vivo. Given the significant functions of NOD2 in innate and adaptive immunity, these next-generation agonists afford new therapeutic leads and adjuvants for a variety of NOD2-responsive diseases. Cold Spring Harbor Laboratory 2023-01-27 /pmc/articles/PMC9901186/ /pubmed/36747725 http://dx.doi.org/10.1101/2023.01.26.525573 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Griffin, Matthew E.
Tsukidate, Taku
Hang, Howard C.
N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
title N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
title_full N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
title_fullStr N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
title_full_unstemmed N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
title_short N-arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy
title_sort n-arylpyrazole nod2 agonists promote immune checkpoint inhibitor therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901186/
https://www.ncbi.nlm.nih.gov/pubmed/36747725
http://dx.doi.org/10.1101/2023.01.26.525573
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