Application of small molecule FPR1 antagonists in the treatment of cancers.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
14 10 2020
Historique:
received: 12 05 2020
accepted: 02 09 2020
entrez: 15 10 2020
pubmed: 16 10 2020
medline: 10 3 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33057069
doi: 10.1038/s41598-020-74350-z
pii: 10.1038/s41598-020-74350-z
pmc: PMC7560711
doi:

Substances chimiques

FPR1 protein, human 0
Fpr1 protein, mouse 0
Receptors, Formyl Peptide 0
Small Molecule Libraries 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17249

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Auteurs

Djevdet S Ahmet (DS)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Haneen A Basheer (HA)

Faculty of Pharmacy, Zarqa University, PO Box 132222, Zarqa, 13132, Jordan.

Anwar Salem (A)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Di Lu (D)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Amin Aghamohammadi (A)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Patrick Weyerhäuser (P)

Institut für Toxikologie, Universitätsmedizin Mainz, Gebäude 905/4. OG, Obere Zahlbacher Str. 67, 55131, Mainz, Germany.

Andrea Bordiga (A)

Dipartimento di Scienza e Tecnologia del Farmaco, Universitá Degli Studi di Torino, Via P. Giuria 9, 10125, Torino, Italy.

Juman Almeniawi (J)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Sabah Rashid (S)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Patricia A Cooper (PA)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Steven D Shnyder (SD)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Victoria Vinader (V)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.

Kamyar Afarinkia (K)

Institute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK. k.afarinkia@bradford.ac.uk.

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Classifications MeSH