BTP2   Click here for help

GtoPdb Ligand ID: 2438

Synonyms: YM-58483
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BTP2 (YM-58483) is a small molecule store-operated Ca2+ release-activated Ca2+ (CRAC) channel inhibitor [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 100.42
Molecular weight 421.04
XLogP 3.51
No. Lipinski's rules broken 0
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Canonical SMILES O=C(c1snnc1C)Nc1ccc(cc1)n1nc(cc1C(F)(F)F)C(F)(F)F
Isomeric SMILES O=C(c1snnc1C)Nc1ccc(cc1)n1nc(cc1C(F)(F)F)C(F)(F)F
InChI InChI=1S/C15H9F6N5OS/c1-7-12(28-25-23-7)13(27)22-8-2-4-9(5-3-8)26-11(15(19,20)21)6-10(24-26)14(16,17)18/h2-6H,1H3,(H,22,27)
Immunopharmacology Comments
CRAC channels form a network essential for activation of the adaptive immune response. They are expressed mainly bt non-excitable cells including T-lymphocytes and mast cells. Activation of CRAC channels in the plasma membranes of these cells results in alteration in NFAT-dependent expression of several cytokines including interleukin-2. Inhibition of calcium influx by altering CRAC channel activity has potential as an effective strategy for the treatment of autoimmune and inflammatory diseases, whilst minimising the adverse effects (nephrotoxicity and neurotoxicity) commonly produced by calcineurin inhibitors used as immunosuppressive agents.

CRAC channels have been implicated in the pathogenesis of rheumatoid arthritis (RA), and inhibitors investigated as clinical candidates for this disease, and others [4]. BTP2 (YM-58483) is a CRAC channel inhibitor. However, despite showing some anti-inflammatory activity in RA models, YM-58483 was associated with safety issues including hepatic and renal toxicity, and hyperglycemia in mice [2].