ArticleBritish journal of pharmacology2009
Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
24 citing papers in PubMed, 48 citations in OpenAlex.
- New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.Journal of medicinal chemistry · 2024Review
- Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.Frontiers in immunology · 2024Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Proteinase-activated receptor-2 antagonist C391 inhibits Alternaria-induced airway epithelial signalling and asthma indicators in acute exposure mouse models.British journal of pharmacology · 2022Article
- Analgesia for Sheep in Commercial Production: Where to Next?Animals : an open access journal from MDPI · 2021Review
- FoxO6-mediated IL-1β induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice.Redox biology · 2019Article
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- PAR2 Modulators Derived from GB88.ACS medicinal chemistry letters · 2016Article
- Teleocidin A2 inhibits human proteinase-activated receptor 2 signaling in tumor cells.Pharmacology research & perspectives · 2016Article
- Pharmacophore-based virtual screening, biological evaluation and binding mode analysis of a novel protease-activated receptor 2 antagonist.Journal of computer-aided molecular design · 2016Article
- The novel PAR2 ligand C391 blocks multiple PAR2 signalling pathways in vitro and in vivo.British journal of pharmacology · 2015Article
- Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury.Critical care (London, England) · 2015Article
- Development of highly potent protease-activated receptor 2 agonists via synthetic lipid tethering.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Lanthanide labeling of a potent protease activated receptor-2 agonist for time-resolved fluorescence analysis.Bioconjugate chemistry · 2012Article
- β-Arrestin-2 mediates the proinflammatory effects of proteinase-activated receptor-2 in the airway.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Modulating human proteinase activated receptor 2 with a novel antagonist (GB88) and agonist (GB110).British journal of pharmacology · 2012Article
- Targeting proteinase-activated receptors: therapeutic potential and challenges.Nature reviews. Drug discovery · 2012Review
- Protease-activated receptor 2 signaling in inflammation.Seminars in immunopathology · 2012Review
- Interdicting protease-activated receptor-2-driven inflammation with cell-penetrating pepducins.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeProteinase-activated receptor 2 (PAR(2)) is a G-protein coupled receptor associated with many pathophysiological functions. To date, the development of PAR(2) antagonists has been limited. Here, we identify a number of novel peptide-mimetic PAR(2) antagonists and demonstrate inhibitory effects on PAR(2)-mediated intracellular signalling pathways and vascular responses. EXPERIMENTAL APPROACH: The peptide-mimetic compound library based on the structures of PAR(2) agonist peptides were screened for inhibition of PAR(2)-induced calcium mobilisation in human keratinocytes. Representative compounds were further evaluated by radioligand binding and inhibition of NFkappaB transcriptional activity and IL-8 production. The vascular effects of the antagonists were assessed using in vitro and in vivo models. KEY
resultsTwo compounds, K-12940 and K-14585, significantly reduced SLIGKV-induced Ca(2+) mobilisation in primary human keratinocytes. Both K-12940 and K-14585 exhibited competitive inhibition for the binding of a high-affinity radiolabelled PAR(2)-ligand, [(3)H]-2-furoyl-LIGRL-NH(2), to human PAR(2) with K(i) values of 1.94 and 0.627 microM respectively. NFkappaB reporter activity and IL-8 production were also significantly reduced. Furthermore, relaxation of rat-isolated aorta induced by SLIGRL-NH(2) was inhibited competitively by K-14585. K-14585 also significantly lowered plasma extravasation in the dorsal skin of guinea pigs and reduced salivation in mice. CONCLUSIONS AND IMPLICATIONS: K-12940 and K-14585 antagonized PAR(2) competitively, resulting in inhibition of PAR(2)-mediated signalling and physiological responses both in vitro and in vivo. These peptide-mimetic PAR(2) antagonists could be useful in evaluating PAR(2)-mediated biological events and might lead to a new generation of therapeutically useful antagonists.
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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 OpenQuestion graph.