YM-58483 (BTP2), a pyrazole derivative, potently inhibits Ca(2+) release-activated Ca(2+) (CRAC) channels and interleukin (IL)-2 production in T cells. YM-58483 inhibited 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). YM-58483 inhibited antigen-induced eosinophil infiltration into airways, and decreased IL-4 and cysteinyl-leukotrienes content in inflammatory airways induced in actively sensitized Brown Norway rats[3]. Intrathecal YM-58483 at the concentration of 300 μM (1.5 nmol) and 1000 μM (10 nmol) produced a significant central analgesic effect on the SNL (spinal nerve ligation) rats, compared with control + vehicle[4]. In the mouse graft-versus-host disease 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 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 response[5].
YM-58483 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SU-DHL-4 cells
3 µM
30 minutes
To investigate the effect of YM-58483 on BIRD-2-induced apoptosis, results showed that YM-58483 did not reduce BIRD-2-induced apoptosis
Cell Death Discov. 2018 Nov 2;4:101.
Human endometrial stromal cells (HESCs)
10 µM
6 days
YM-58483 significantly decreased COX2, BMP2, and WNT4 transcript levels
J Mol Med (Berl). 2018 Feb;96(2):173-182.
Human B cells
50 nM
72 hours
To investigate the effect of YM-58483 on B cell differentiation, results showed that YM-58483 suppressed B cell differentiation and reduced IgG production.
Front Immunol. 2021 Oct 22;12:779560.
Spinal astrocytes
3 µM
YM-58483 significantly prevented the calcium influx induced by TG, indicating its inhibition of SOCE in spinal astrocytes.
J Neuroinflammation. 2016 May 31;13(1):126.
YM-58483 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Hindlimb ischaemia model
Mini-osmotic pump
0.1 mg/kg/day
Once daily for 3 or 7 days
YM-58483 promoted post-ischaemic blood flow recovery by inhibiting TRPC6 channel activity, particularly in hypercholesterolemic models, where it significantly improved blood flow recovery and endothelial function.
Br J Pharmacol. 2023 Jan;180(1):94-110
Mice
MRL/lpr lupus mice
Intraperitoneal injection
1 mg/kg
Once daily for 6 weeks
To investigate the therapeutic effect of YM-58483 on lupus nephritis, results showed that YM-58483 ameliorated kidney damage, reduced the percentage of plasma cells in the spleen, and decreased the level of anti-double-stranded DNA antibodies in the serum.
To investigate the analgesic effects of YM-58483 in acute and chronic pain models. The results showed that YM-58483 significantly attenuated CFA- and SNI-induced pain hypersensitivity and reduced formalin-induced spontaneous nociceptive behavior.
Pain. 2013 Oct;154(10):2034-2044
Rats
Aged rat coronary arteries
In vitro administration
20 µM
Single dose, 30 minutes exposure
YM-58483 significantly inhibited 5-HT and ET-1-induced contractions in coronary arteries from aged rats and improved endothelium-dependent vasodilation in aged rat coronary arteries.
Int J Mol Sci. 2023 Aug 29;24(17):13402
DBA/1 mice
Collagen-induced arthritis (CIA) model
Oral
5 or 10 mg/kg
Daily administration for 10 days
YM-58483 significantly reduced the incidence of CIA, prevented the development of inflammation and pain hypersensitivity, and improved other symptoms of arthritis.
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