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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Published inScientific reports Vol. 10; no. 1; p. 17249
Main Authors 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 14.10.2020
Subjects
631/67/1059
631/67/2195
631/67/322
631/67/327
Animals
Cell Line, Tumor
Humanities and Social Sciences
Humans
Mice, Inbred BALB C
multidisciplinary
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Receptors, Formyl Peptide - antagonists & inhibitors
Receptors, Formyl Peptide - genetics
Receptors, Formyl Peptide - metabolism
Science
Science (multidisciplinary)
Small Molecule Libraries - administration & dosage
Online AccessGet full text

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Abstract 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.
AbstractList 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.
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.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.
ArticleNumber 17249
Author Shnyder, Steven D.
Basheer, Haneen A.
Rashid, Sabah
Vinader, Victoria
Weyerhäuser, Patrick
Bordiga, Andrea
Ahmet, Djevdet S.
Salem, Anwar
Afarinkia, Kamyar
Almeniawi, Juman
Lu, Di
Aghamohammadi, Amin
Cooper, Patricia A.
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Snippet The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of...
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springer
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SubjectTerms 631/67/1059
631/67/2195
631/67/322
631/67/327
Animals
Cell Line, Tumor
Humanities and Social Sciences
Humans
Mice, Inbred BALB C
multidisciplinary
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Receptors, Formyl Peptide - antagonists & inhibitors
Receptors, Formyl Peptide - genetics
Receptors, Formyl Peptide - metabolism
Science
Science (multidisciplinary)
Small Molecule Libraries - administration & dosage
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Title Application of small molecule FPR1 antagonists in the treatment of cancers
URI https://link.springer.com/article/10.1038/s41598-020-74350-z
https://www.ncbi.nlm.nih.gov/pubmed/33057069
https://www.proquest.com/docview/2451859680
https://pubmed.ncbi.nlm.nih.gov/PMC7560711
Volume 10
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