ArticleCommunications biology2020
Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- Recent Advances in GPCR Ligand Discovery Using DNA-Encoded Library Technology: From Affinity Binding to Functional Bias and Allosteric Modulation.ACS medicinal chemistry letters · 2026Review
- MMP1 and PRSS23 induce PARCommunications biology · 2026Article
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026Review
- Structural basis of protease-activated receptor 2 activation and biased agonism.Cell discovery · 2025Article
- Selective PAR2 Inhibition Attenuates HDM-Induced Th1/Th2 Responses in Human Epithelial and Murine Models of Allergic Rhinitis and Asthma.International forum of allergy & rhinology · 2025Article
- Epigallocatechin Gallate as a Molecular Therapeutic in Heart Failure and Cardio-Oncology: Mechanistic Pathways and Translational Perspectives.International journal of molecular sciences · 2025Review
- Article
- Blockade of PAR2 Signaling by Punicalagin as a Therapeutic Strategy for Atopic Dermatitis.International journal of molecular sciences · 2025Article
- Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.International journal of molecular sciences · 2025Review
- Structural basis for the activation of proteinase-activated receptors PAR1 and PAR2.Nature communications · 2025Article
- PARBiomaterials · 2025Article
- PAR1-mediated Non-periodical Synchronized Calcium Oscillations in Human Mesangial Cells.Function (Oxford, England) · 2024Article
- Targeting TRPV4 Channels for Cancer Pain Relief.Cancers · 2024Review
- Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.Frontiers in immunology · 2024Review
- TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells.Cancers · 2023Article
- Protease-activated receptor 2 attenuates doxorubicin-induced apoptosis in colon cancer cells.Journal of cell communication and signaling · 2023Article
- Impact of library input on the hit discovery rate in DNA-encoded chemical library selections.Chemical science · 2023Article
- 1-Piperidine Propionic Acid as an Allosteric Inhibitor of Protease Activated Receptor-2.Pharmaceuticals (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protease-activated receptor-2 (PAR2) has been implicated in multiple pathophysiologies but drug discovery is challenging due to low small molecule tractability and a complex activation mechanism. Here we report the pharmacological profiling of a potent new agonist, suggested by molecular modelling to bind in the putative orthosteric site, and two novel PAR2 antagonists with distinctly different mechanisms of inhibition. We identify coupling between different PAR2 binding sites. One antagonist is a competitive inhibitor that binds to the orthosteric site, while a second antagonist is a negative allosteric modulator that binds at a remote site. The allosteric modulator shows probe dependence, more effectively inhibiting peptide than protease activation of PAR2 signalling. Importantly, both antagonists are active in vivo, inhibiting PAR2 agonist-induced acute paw inflammation in rats and preventing activation of mast cells and neutrophils. These results highlight two distinct mechanisms of inhibition that potentially could be targeted for future development of drugs that modulate PAR2.
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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.