Siponimod

Research use only, not for human use.

Siponimod (BAF312) is a potent, selective S1P1/S1P5 receptor modulator with EC50 of 0.39/0.0.98 nM.

Siponimod (BAF312) is a potent, selective S1P1/S1P5 receptor modulator with EC50 of 0.39/0.0.98 nM, >1,000-fold selectivity over S1P2/3/4; suppresses ongoing disease symptoms in rat EAE, concentration-dependently increases GIRK current amplitude in atrial myocytes with EC50 of 15.8 nM, reduces peripheral absolute lymphocyte counts in vivo, exhibits potential as a treatment for immune-mediated diseases.Multiple Sclerosis Phase 3 Clinical(In Vitro):Siponimod (compound 32) exhibits selectivity to S1P1 and S1P5, and spares activity on the S1P2, S1P3 and S1P4 receptors.Siponimod (1 mM; 0-1 h) promotes internalization of S1P1 receptors, results 94% S1P1 receptors localized intracellularly at 1 h.Siponimod (0.001 nM-1 μM; 1 h) activates the GIRK channel in atrial myocytes, with an EC50 value of 15.8 nM in CHO cell line CCL-61.(In Vivo):Siponimod (1 g/kg; i.v.; single dose) shows low to moderate in monkey, but high in rat in metabolism studies with liver microsomes. The absolute bioavailability is 50 and 71% in the rat and monkey, respectively, indicating no major presystemic first pass metabolism.Siponimod (0.3, 3 mg/kg; p.o.; once daily; 23 d) suppresses experimental autoimmune encephalomyelitis (EAE) in rats by internalizing S1P1 receptors.

Siponimod (compound 32) exhibits selectivity to S1P1 and S1P5, and spares activity on the S1P2, S1P3 and S1P4 receptors.Siponimod (1 mM; 0-1 h) promotes internalization of S1P1 receptors, results 94% S1P1 receptorslocalized intracellularly at 1 h.Siponimod (0.001 nM-1 μM; 1 h) activates the GIRK channel in atrial myocytes, with an EC50 value of 15.8 nM in CHO cell line CCL-61.

Siponimod (1 g/kg; i.v.; single dose) shows low to moderate in monkey, but high in rat in metabolism studies with liver microsomes. The absolute bioavailability is 50 and 71% in the rat and monkey, respectively, indicating no major presystemic first pass metabolism.Siponimod (0.3, 3 mg/kg; p.o.; once daily; 23 d) suppresses experimental autoimmune encephalomyelitis (EAE) in rats by internalizing S1P1 receptors. Animal Model: Experimental autoimmune encephalomyelitis (EAE) model in Lewis rats (200-250 g)Dosage:0.03, 0.3, 3 mg/kg Administration:Oral gavage; once daily; 23 days Result:Decreased peripheral lymphocyte counts by 88% at the Tmax of 8 h postadministration.

BAF-312

GPCR/G Protein

Lysophospholipid Receptor

S1P1|S1P2|S1P3|S1P4|S1P5

Inflammation/Immunology

Multiple Sclerosis

1230487-00-9

516.595

C29H35F3N2O3

>98% (HPLC)

DMSO: ≥ 30 mg/mL

CCC1=C(CN2CC(C(O)=O)C2)C=CC(/C(C)=N/OCC3=CC(C(F)(F)F)=C(C4CCCCC4)C=C3)=C1

3-Azetidinecarboxylic acid, 1-[[4-[(1E)-1-[[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]imino]ethyl]-2-ethylphenyl]methyl]-

(-20℃)

With Ice Pack

≥ 2 years