Characterization of YM-58483/BTP2, a novel store-operated Ca2+ entry blocker, on T cell-mediated immune responses in vivo

Int Immunopharmacol. 2008 Dec 20;8(13-14):1787-92. doi: 10.1016/j.intimp.2008.08.016. Epub 2008 Sep 13.


YM-58483/BTP2 is a blocker of store-operated Ca2+ entry (SOCE), which regulates the activation of non-excitable cells such as lymphocytes. YM-58483 has been reported to inhibit cytokine production and proliferation in T cells, and to be useful as a probable medicinal candidate for treatment of bronchial asthma. The present study investigated the pharmacological profile and therapeutic potential of YM-58483 in relation to cell-mediated immune responses. 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.) inhibited donor anti-host cytotoxic T lymphocyte (CTL) activity and IFN-gamma production, and also reduced the number of donor T cells, especially donor CD8+ T cells, in the spleen. YM-58483 and cyclosporine A inhibited T cell proliferation in a one-way mixed lymphocyte reaction (MLR) with IC50 values of 330 and 12.7 nM, respectively. Additionally, YM-58483 (1-10 mg/kg, p.o.) and cyclosporine A (2, 10 mg/kg, p.o.) inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) response. These results suggest that the inhibition of SOCE leads to the prevention of antigen-induced T cell responses, which participate in autoimmune diseases such as autoimmune hepatitis and rheumatoid arthritis.

MeSH terms

  • Anilides / pharmacology*
  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Calcium Channel Blockers / pharmacology*
  • Cyclosporine / pharmacology
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / metabolism
  • Hypersensitivity, Delayed / immunology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Interferon-gamma / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Thiadiazoles / pharmacology*


  • 4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide
  • Anilides
  • Calcium Channel Blockers
  • Thiadiazoles
  • Interferon-gamma
  • Cyclosporine