ArticleThe Biochemical journal2015
Down-regulation of PAR1 activity with a pHLIP-based allosteric antagonist induces cancer cell death.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Selective Recruitment of Antibodies to Cancer Cells and Immune Cell-mediated Killing via In Situ Click Chemistry.ChemMedChem · 2024Article
- Targeted acidosis mediated delivery of antigenic MHC-binding peptides.Frontiers in immunology · 2024Article
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Promoting the activity of a receptor tyrosine phosphatase with a novel pH-responsive transmembrane agonist inhibits cancer-associated phenotypes.Protein science : a publication of the Protein Society · 2023Article
- Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells.Chembiochem : a European journal of chemical biology · 2022Article
- PET Imaging of Acidic Tumor Environment WithFrontiers in oncology · 2022Article
- An Experimental Study on [Molecular imaging · 2021Article
- pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity.Journal of medicinal chemistry · 2020Article
- pHLIP(Var7)-P1AP suppresses tumor cell proliferation in MDA-MB-231 triple-negative breast cancer by targeting protease activated receptor 1.Breast cancer research and treatment · 2020Article
- Inhibiting Epidermal Growth Factor Receptor Dimerization and Signaling Through Targeted Delivery of a Juxtamembrane Domain Peptide Mimic.ACS chemical biology · 2018Article
- Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Comparison of lipid-dependent bilayer insertion of pHLIP and its P20G variant.Biochimica et biophysica acta. Biomembranes · 2018Article
- Exploiting cancer's phenotypic guise against itself: targeting ectopically expressed peptide G-protein coupled receptors for lung cancer therapy.Oncotarget · 2017Review
- Targeting PAR1: Now What?Trends in pharmacological sciences · 2017Review
- Applications of pHLIP Technology for Cancer Imaging and Therapy.Trends in biotechnology · 2017Review
- Therapeutic Efficacy of a Family of pHLIP-MMAF Conjugates in Cancer Cells and Mouse Models.Molecular pharmaceutics · 2017Article
- pHLIP Peptide Interaction with a Membrane Monitored by SAXS.The journal of physical chemistry. B · 2016Article
- pH-Selective Cytotoxicity of pHLIP-Antimicrobial Peptide Conjugates.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Even though abnormal expression of G protein-coupled receptors (GPCRs) and of their ligands is observed in many cancer cells of various origins, only a few anti-cancer compounds directly act on their signalling. One promising approach to modulate their activity consists of targeting the receptor cytoplasmic surfaces interacting with the associated G-proteins using peptides mimicking the intracellular loops of the receptor. Thus, to be fully effective, the peptide mimics must be selectively targeted to the tumour while sparing healthy tissues, translocated across the cell membrane and stay anchored to the cytoplasmic leaflet of the plasma membrane. In the present study, we introduce a novel way to selectively target and inhibit the activity of a GPCR in cancer cells under acidic conditions, such as those found in solid tumours. We find that the conjugation of a peptide fragment derived from the third intracellular loop (i3) of the protease-activated receptor 1 (PAR1) to a peptide that can selectively target tumours solely based on their acidity [pH(Low) Insertion Peptide (pHLIP)], produces a construct capable of effectively down-regulating PAR1 activity in a concentration- and pH-dependent manner and of inducing a potent cytotoxic effect in a panel of cancer cells that is proportional to the relative level of receptor expression at the cell surface. This strategy not only allows for a more selective targeting and specific intracellular delivery than current approaches, but also offers new possibilities for developing novel anti-cancer drugs targeting GPCRs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.