YM-58483

YM-58483 (BTP2) is the first selective and potent inhibitor of CRAC channels and subsequent Ca²⁺ signals^[1]. YM-584832 is a blocker of store-operated Ca²⁺ entry (SOCE)^[2]. In Vitro: YM-58483 can decrease the levels of P-ERK and P-CREB, without affecting the expression of CD11b and GFAP. YM-58483 also inhibits the release of spinal cord IL-1β, TNF-α, and PGE2^[1]. YM-58483 and cyclosporine A inhibits T cell proliferation in a one-way mixed lymphocyte reaction (mLR) with IC₅₀ values of 330 and 12.7 nM, respectively^[2]. YM-58483 inhibits DNP antigen-induced histamine release from and leukotrienes (LTs) production in IgE-primed RBL-2H3 cells, a rat basophilic leukemia cell line, with IC₅₀ values of 460 and 310 nM, respectively. YM-58483 also inhibits phytohemagglutinin-P (PHA)-stimulated IL-5 and IL-13 production in human peripheral blood cells with IC₅₀ values of 125 and 148 nM, respectively, which is approximately 5 times less potent than prednisolone^[3]. YM-58483 inhibits IL-4 and IL-5 production in a conalbumine-stimulated murine Th2 T cell clone (D10.G4.1), and IL-5 production in phytohemagglutinin-stimulated human whole blood cells with IC₅₀ values comparable to those reported for its CRAC channel inhibition (around 100 nM)^[4]. In Vivo: Intrathecal YM-58483 at the concentration of 300 μM (1.5 nmol) and 1000 μM (10 nmol) produces a significant central analgesic effect on the SNL rats^[1]. In the mouse graft-versus-host disease (GVHD) model, YM-58483 (1-30 mg/kg, p.o.) and cyclosporine A (1-30 mg/kg, p.o.) inhibit donor anti-host cytotoxic T lymphocyte (CTL) activity and IFN-γ production, and also reduce the number of donor T cells, especially donor CD8⁺ T cells, in the spleen. YM-58483 (1-10 mg/kg, p.o.) and cyclosporine A (2, 10 mg/kg, p.o.) inhibit the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) response^[2]. M-58483 (30 mg/kg, p.o.) significantly suppresses ovalbumin (OVA)-induced bronchoconstriction in OVA-sensitized guinea pigs, whereas prednisolone does not. YM-58483 (3-30 mg/kg, p.o.) and prednisolone (100 mg/kg, p.o.) both significantly and completely suppress airway hyperresponsiveness (AHR) caused by OVA exposure^[3]. YM-58483 inhibits antigen-induced eosinophil infiltration into airways, and decreases IL-4 and cysteinyl-leukotrienes content in inflammatory airways induced in actively sensitized Brown Norway rats. Orally administered YM-58483 prevents antigen-induced late phase asthmatic broncoconstriction and eosinophil infiltration in actively sensitized guinea pigs^[4].