A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening

We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in...

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Detalles Bibliográficos
Autores principales: Proj, Matic, De Jonghe, Steven, Van Loy, Tom, Jukič, Marko, Meden, Anže, Ciber, Luka, Podlipnik, Črtomir, Grošelj, Uroš, Konc, Janez, Schols, Dominique, Gobec, Stanislav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Pharmacology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972196/
https://www.ncbi.nlm.nih.gov/pubmed/35370691
http://dx.doi.org/10.3389/fphar.2022.855653
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author Proj, Matic
De Jonghe, Steven
Van Loy, Tom
Jukič, Marko
Meden, Anže
Ciber, Luka
Podlipnik, Črtomir
Grošelj, Uroš
Konc, Janez
Schols, Dominique
Gobec, Stanislav
author_facet Proj, Matic
De Jonghe, Steven
Van Loy, Tom
Jukič, Marko
Meden, Anže
Ciber, Luka
Podlipnik, Črtomir
Grošelj, Uroš
Konc, Janez
Schols, Dominique
Gobec, Stanislav
author_sort Proj, Matic
collection PubMed
description We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in drug discovery and there are no potent and selective CCR7 small molecule antagonists available today. Therefore, computer-aided ligand-based, structure-based, and joint virtual screening campaigns were performed. Hits from these virtual screenings were tested in a CCL19-induced calcium signaling assay. After careful evaluation, none of the in silico hits were confirmed to have an antagonistic effect on CCR7. Hence, we report here a valuable set of 287 inactive compounds that can be used as experimentally validated decoys.
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spelling pubmed-89721962022-04-02 A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening Proj, Matic De Jonghe, Steven Van Loy, Tom Jukič, Marko Meden, Anže Ciber, Luka Podlipnik, Črtomir Grošelj, Uroš Konc, Janez Schols, Dominique Gobec, Stanislav Front Pharmacol Pharmacology We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in drug discovery and there are no potent and selective CCR7 small molecule antagonists available today. Therefore, computer-aided ligand-based, structure-based, and joint virtual screening campaigns were performed. Hits from these virtual screenings were tested in a CCL19-induced calcium signaling assay. After careful evaluation, none of the in silico hits were confirmed to have an antagonistic effect on CCR7. Hence, we report here a valuable set of 287 inactive compounds that can be used as experimentally validated decoys. Frontiers Media S.A. 2022-03-18 /pmc/articles/PMC8972196/ /pubmed/35370691 http://dx.doi.org/10.3389/fphar.2022.855653 Text en Copyright © 2022 Proj, De Jonghe, Van Loy, Jukič, Meden, Ciber, Podlipnik, Grošelj, Konc, Schols and Gobec. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Proj, Matic
De Jonghe, Steven
Van Loy, Tom
Jukič, Marko
Meden, Anže
Ciber, Luka
Podlipnik, Črtomir
Grošelj, Uroš
Konc, Janez
Schols, Dominique
Gobec, Stanislav
A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening
title A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening
title_full A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening
title_fullStr A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening
title_full_unstemmed A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening
title_short A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening
title_sort set of experimentally validated decoys for the human cc chemokine receptor 7 (ccr7) obtained by virtual screening
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8972196/
https://www.ncbi.nlm.nih.gov/pubmed/35370691
http://dx.doi.org/10.3389/fphar.2022.855653
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