Siponimod

• CAT Number: I009494
• CAS Number: 1230487-00-9
• Molecular Formula: C29H35F3N2O3
• Molecular Weight: 516.60
• Purity: 98%
• Synonyms: BAF-312; BAF 312; BAF312; Siponimod;(E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid
• Target: S1P1；S1P5
• Target Protein: Q9H228,P21453
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid
• Storage: Dry, dark and at 2 - 8 °C for six months or -20°C for two years.
• IC50: S1PR1：0.39 nM (EC50)
• IUPAC Name: 1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid
• InChI: InChI=1S/C29H35F3N2O3/c1-3-21-14-23(10-11-24(21)15-34-16-25(17-34)28(35)36)19(2)33-37-18-20-9-12-26(22-7-5-4-6-8-22)27(13-20)29(30,31)32/h9-14,22,25H,3-8,15-18H2,1-2H3,(H,35,36)/b33-19+
• InChIKey: KIHYPELVXPAIDH-HNSNBQBZSA-N
• SMILES: CCC1=C(C=CC(=C1)/C(=N/OCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)/C)CN4CC(C4)C(=O)O

Siponimod (Cat No.: I009494), also known as BAF-312, is a potent and orally selective S1P (sphingosine-1-phosphate) receptor modulator. It exhibits high affinity and selectivity for S1P1 and S1P5 receptors, with EC50 values of 0.39nM and 0.98nM, respectively. By targeting these receptors, siponimod regulates the function of immune cells and dampens inflammation. This mechanism of action makes it a promising candidate for treating medical conditions characterized by significant immunopathology. Siponimod has shown potential in the treatment of multiple sclerosis and is being investigated for other autoimmune and inflammatory disorders.

Overview of Clinical Research

Siponimod is a Sphingosine 1 phosphate receptor modulator. It has been granted for the new molecular entity.

Reference

1. Drug Des Devel Ther. 2017 Nov 2;11:3153-3157. doi: 10.2147/DDDT.S122249. eCollection 2017.

Spotlight on siponimod and its potential in the treatment of secondary progressive multiple sclerosis: the evidence to date.

Gajofatto A(1).
Author information:
(1)Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Siponimod (BAF312) is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs. Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing-remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction. In addition, S1P1 and S1P5 receptors are expressed by neurons and glia and could mediate a possible neuroprotective effect of the drug. A Phase II clinical trial of siponimod for RR MS showed a significant effect of the active drug compared to placebo on reducing gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) after 3 months of treatment. In a recently completed Phase III trial, treatment with siponimod was associated with a significant reduction in disability progression in secondary progressive (SP) MS patients compared to placebo. In this article, current evidence supporting siponimod efficacy for SP MS is reviewed.