ArticleBritish journal of pharmacology2019
GSK2646264, a spleen tyrosine kinase inhibitor, attenuates the release of histamine in ex vivo human skin.
Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study.Experimental dermatology · 2021Trial
- Aberrant Activation of Mast Cells: Molecular Mechanisms and Targets for Intervention.Clinical reviews in allergy & immunology · 2025Review
- Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74.Frontiers in immunology · 2024Article
- Current and Emerging Therapies for Chronic Spontaneous Urticaria: A Narrative Review.Dermatology and therapy · 2023Review
- Understanding human mast cells: lesson from therapies for allergic and non-allergic diseases.Nature reviews. Immunology · 2022Review
- Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation.International journal of molecular sciences · 2022Review
- Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation.Cells · 2021Review
- A Comprehensive Approach to Urticaria: From Clinical Presentation to Modern Biological Treatments Through Pathogenesis.Advances in experimental medicine and biology · 2021Article
- Review
- Current and emerging treatments for chronic spontaneous urticaria.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2020Review
- Targeting the FcεRI Pathway as a Potential Strategy to Prevent Food-Induced Anaphylaxis.Frontiers in immunology · 2020Review
- Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020.International archives of allergy and immunology · 2020Review
- Emerging Therapies in Chronic Spontaneous Urticaria.Allergy, asthma & immunology research · 2019Review
- GSK2646264, a spleen tyrosine kinase inhibitor, attenuates the release of histamine in ex vivo human skin.British journal of pharmacology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeChronic spontaneous urticaria presents as a heterogeneous syndrome characterised by wheals, angioedema, or both for greater than 6 weeks. Spleen tyrosine kinase mediates allergen-induced mast cell degranulation via the IgE signalling pathway, a central component of wheal formation and inflammation. In this study, we investigated the effects of perfused or topically administered GSK2646264 on IgE-mediated histamine release from mast cells in an ex vivo human skin model. EXPERIMENTAL APPROACH: Using a novel SkiP device, ex vivo human skin from mastectomy surgeries was challenged with anti-IgE, complement 5a (C5a), and buffer to induce histamine release from skin mast cells. Histamine was collected via microdialysis fibres and measured fluorometrically. GSK2646264 was delivered via perfusion either using microdialysis fibres or topically in a cream. Drug concentrations in the skin were measured by LC-MS, and a pharmacokinetic/ pharmacodynamic (PK/PD) relationship developed. KEY
resultsPerfused GSK2646264 significantly inhibited anti-IgE (but not C5a)-induced histamine release in a concentration-dependent manner. The 0.5, 1, and 3% cream delivered GSK2646264 to the dermis above the IC CONCLUSIONS AND IMPLICATIONS: GSK2646264 administered topically or direct to the dermis blocked histamine release from in situ skin mast cells. A PK/PD relationship curve suggests that dermal concentrations above 6.8 μM should lead to approximately 90% inhibition of histamine release from skin mast cells following activation of the Fc fragment of IgE receptor 1a, implicating a potential use for the compound in skin mast cell diseases such as urticaria.
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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.