BAF312 (Siponimod)

Catalog No.S7179

BAF312 (Siponimod) Chemical Structure

Molecular Weight(MW): 516.6

BAF312 (Siponimod) is a next-generation S1P receptor modulator, selective for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, exhibits >1000-fold selectivity over S1P2, S1P3 and S1P4 receptors. Phase 3.

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Description BAF312 (Siponimod) is a next-generation S1P receptor modulator, selective for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, exhibits >1000-fold selectivity over S1P2, S1P3 and S1P4 receptors. Phase 3.
S1P1 receptor [1] S1P5 receptor [1] S1P4 receptor [1] S1P3 receptor [1] S1P2 receptor [1]
0.39 nM(EC50) 0.98 nM(EC50) 750 nM(EC50) >1 μM(EC50) >10 μM(EC50)
In vitro

BAF312 (Siponimod) is a potent and selective S1P receptor agonist, with EC50 of 0.39 nM and 0.98 nM for S1P1 and S1P5receptors, exhibits >1000-fold selectivity over S1P2, S1P3 and S1P4 receptors. [1]BAF312 (1 h at 1 μM) promotes prominent internalization of S1P1 receptors by 91%.[2]

In vivo BAF312 effectively suppresses encephalomyelitis (EAE) in rats by internalizing S1P1 receptors, rendering them insensitive to the egress signal from lymph nodes. [1] BAF312 significantly reduces clinical scores when dosed prophylactically or therapeutically in mice at 0.3 mg/kg. [3]


Kinase Assay:[1]
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GTPγ[35S] binding assay:

The cells are homogenized and centrifuged at 26900 × g for 30 min at 4°C. Membranes are re-suspended in 20 mM HEPES (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA and 0.1% fat-free BSA at 2–3 mg protein/mL. GTPγ[35S] binding assay is performed with the membranes (75 mg protein /mL in 50 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 20 μg/mL saponin and 0.1% fat-free BSA (pH 7.4), 5 mg/mL with wheat-germ agglutinin-coated scintillation proximity assay-bead, and 10 μM GDP for 10–15 min. The GTPγ[35S]-binding reaction is started by the addition of 200 pM GTPγ[35S]. After 120 min at room temperature, the plates are centrifuged for 10 min at 300 × g and counted.
Cell Research: [1]
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  • Cell lines: CHO
  • Concentrations: ~1 μM
  • Incubation Time: 1 h
  • Method: Agonist-mediated internalization of S1P1 receptors in CHO cells analysed by flow cytometry Myc-tag hS1P1 cells are incubated for 1 h with agonist at 37°C in standard culture medium followed by a PBS wash. An aliquot is kept on ice for 3 h, while another aliquot is left for 3 (or 12) h in culture medium (no agonist) at 37°C. The cells are then incubated either with 4 μg/mL monoclonal mouse anti C-myc IgG1 antibody or with isotype control mouse IgG1 for 60 min at 4°C, followed by an incubation with 1 μg/mL of Alexa488-labelled goat anti-mouse secondary conjugates. The cells are subjected to flow cytometry measurements using 10000 viable cells per sample.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: encephalomyelitis (EAE) model rat
  • Formulation: suspended in 1% aqueous carboxy-methylcellulose
  • Dosages: 0.03, 0.3 and 3 mg/kg
  • Administration: oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL warmed (193.57 mM)
Ethanol 44 mg/mL warmed (85.17 mM)
Water <1 mg/mL
In vivo

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 516.6


CAS No. 1230487-00-9
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02029274 Completed Active Dermatomyositis Novartis Pharmaceuticals|Novartis November 2013 Phase 2
NCT01904214 Completed Renal Impairment Novartis Pharmaceuticals|Novartis July 2013 Phase 1
NCT01801917 Completed Polymyositis Novartis Pharmaceuticals|Novartis April 2013 Phase 2
NCT01665144 Active, not recruiting Secondary Progressive Multiple Sclerosis Novartis Pharmaceuticals|Novartis December 2012 Phase 3
NCT01565902 Completed Hepatic Impairment Novartis Pharmaceuticals|Novartis October 2012 Phase 1
NCT01185821 Recruiting Relapsing Remitting Multiple Sclerosis|Autoimmune Diseases|Immune System Diseases|Nervous System Diseases|Autoimmune Diseases of the Nervous System Novartis Pharmaceuticals|Novartis August 2010 Phase 2

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S1P Receptor Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID