biostudies-literatureMamorita SInnovative Drug Discovery and Life Science Research from AMEDJSPS KAKENHINipponham Foundation for the Future of Food, KOSÉ Cosmetology Research Foundation, Hoyu Science Foundation, Naito Foundation, and Takeda Science Foundatione70152https://www.ebi.ac.uk/biostudies/studies/S-EPMC12925385biostudies-literatureUnknown56(2)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 membEuropean journal of immunologyDiscovery of Lomitapide as a Novel Mast Cell Regulatory Agent Through Chemical Library Screening.PMC12925385JP23ama12105319H0336916H05082Suzuki RMamorita SNagata YFurukawa AfalseDiscovery of Lomitapide as a Novel Mast Cell Regulatory Agent Through Chemical Library Screening.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 memb2026-01-01T00:00:00Z2026 Feb2026-07-16T15:18:41.24Z2026-07-11T03:07:57.449ZS-EPMC129253854172372610.1002/eji.70152