ArticleEuropean journal of immunology2026
Discovery of Lomitapide as a Novel Mast Cell Regulatory Agent Through Chemical Library Screening.
Article in European journal of immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Allergic diseases are a global health concern, and new molecular insights and therapeutic agents are necessary to support future research and interventions. Mast cells (MCs) play a crucial role in allergic reactions, in which antigen (Ag) cross-linking of high-affinity receptors (FcεRI) activates signaling pathways, leading to the release of various types of inflammatory mediators. We developed a chemical library screening system using RBL-2H3 cells, a widely used MC model, to identify anti-allergic agents. This method revealed that lomitapide, a microsomal triglyceride transfer protein (MTTP) inhibitor, is a novel MC regulatory agent. Furthermore, lomitapide was found to inhibit MC degranulation by altering MC plasma membrane dynamics, specifically by preventing endocytosis of plasma membrane components, rather than through the conventional MTTP-inhibiting mechanism. Additionally, experiments using a passive cutaneous anaphylaxis (PCA) mouse model demonstrated that lomitapide dampened anaphylactic reactions in vivo. These findings indicate that lomitapide effectively inhibits MC degranulation, which affects allergic responses, suggesting that lomitapide exhibits a novel MC regulatory function and has potential as an anti-allergic therapeutic agent.
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