Application of small molecule FPR1 antagonists in the treatment of cancers

The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of ca...

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Autores principales: Ahmet, Djevdet S., Basheer, Haneen A., Salem, Anwar, Lu, Di, Aghamohammadi, Amin, Weyerhäuser, Patrick, Bordiga, Andrea, Almeniawi, Juman, Rashid, Sabah, Cooper, Patricia A., Shnyder, Steven D., Vinader, Victoria, Afarinkia, Kamyar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560711/
https://www.ncbi.nlm.nih.gov/pubmed/33057069
http://dx.doi.org/10.1038/s41598-020-74350-z
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author Ahmet, Djevdet S.
Basheer, Haneen A.
Salem, Anwar
Lu, Di
Aghamohammadi, Amin
Weyerhäuser, Patrick
Bordiga, Andrea
Almeniawi, Juman
Rashid, Sabah
Cooper, Patricia A.
Shnyder, Steven D.
Vinader, Victoria
Afarinkia, Kamyar
author_facet Ahmet, Djevdet S.
Basheer, Haneen A.
Salem, Anwar
Lu, Di
Aghamohammadi, Amin
Weyerhäuser, Patrick
Bordiga, Andrea
Almeniawi, Juman
Rashid, Sabah
Cooper, Patricia A.
Shnyder, Steven D.
Vinader, Victoria
Afarinkia, Kamyar
author_sort Ahmet, Djevdet S.
collection PubMed
description The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of cancer and in this context, plays a significant role in their expansion, resistance and recurrence. ICT12035 is a selective and potent (30 nM in calcium mobilisation assay) small molecule FPR1 antagonist. Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D proliferation and invasion in vitro assays and an in vivo model. Our results demonstrate that targeting FPR1 by a selective small molecule antagonist, such as ICT12035, can provide a new avenue for the treatment of cancers.
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spelling pubmed-75607112020-10-19 Application of small molecule FPR1 antagonists in the treatment of cancers Ahmet, Djevdet S. Basheer, Haneen A. Salem, Anwar Lu, Di Aghamohammadi, Amin Weyerhäuser, Patrick Bordiga, Andrea Almeniawi, Juman Rashid, Sabah Cooper, Patricia A. Shnyder, Steven D. Vinader, Victoria Afarinkia, Kamyar Sci Rep Article The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of cancer and in this context, plays a significant role in their expansion, resistance and recurrence. ICT12035 is a selective and potent (30 nM in calcium mobilisation assay) small molecule FPR1 antagonist. Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D proliferation and invasion in vitro assays and an in vivo model. Our results demonstrate that targeting FPR1 by a selective small molecule antagonist, such as ICT12035, can provide a new avenue for the treatment of cancers. Nature Publishing Group UK 2020-10-14 /pmc/articles/PMC7560711/ /pubmed/33057069 http://dx.doi.org/10.1038/s41598-020-74350-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ahmet, Djevdet S.
Basheer, Haneen A.
Salem, Anwar
Lu, Di
Aghamohammadi, Amin
Weyerhäuser, Patrick
Bordiga, Andrea
Almeniawi, Juman
Rashid, Sabah
Cooper, Patricia A.
Shnyder, Steven D.
Vinader, Victoria
Afarinkia, Kamyar
Application of small molecule FPR1 antagonists in the treatment of cancers
title Application of small molecule FPR1 antagonists in the treatment of cancers
title_full Application of small molecule FPR1 antagonists in the treatment of cancers
title_fullStr Application of small molecule FPR1 antagonists in the treatment of cancers
title_full_unstemmed Application of small molecule FPR1 antagonists in the treatment of cancers
title_short Application of small molecule FPR1 antagonists in the treatment of cancers
title_sort application of small molecule fpr1 antagonists in the treatment of cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560711/
https://www.ncbi.nlm.nih.gov/pubmed/33057069
http://dx.doi.org/10.1038/s41598-020-74350-z
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