Siponimod (BAF-312) by Nutrabiotech, high purity multiple sclerosis treatment compound for biomedical and pharmaceutical research

Siponimod BAF312 CAS 1230487-00-9 High Purity Powder Selective S1PR1/S1PR5 Modulator Multiple Sclerosis Research Reagent

High-purity Siponimod powder CAS 1230487-00-9, also known as BAF312, is a highly selective, orally active S1PR1 and S1PR5 dual receptor modulator. This off-white crystalline small molecule induces S1P1 receptor internalization, blocks lymphocyte egress from lymph nodes, reduces peripheral immune cell infiltration into the central nervous system, and suppresses neuroinflammation. It also promotes myelin repair and protects neuronal synapses, widely used in laboratory research on secondary progressive multiple sclerosis, relapsing multiple sclerosis, autoimmune neuroinflammation and demyelinating disease mechanism studies. High-purity bulk powder and customized packaging are available for global pharmacology and neuroscience research buyers.

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Siponimod (CAS 1230487-00-9) Selective S1P1/S1P5 Receptor Modulator | BAF-312 Mayzent SPMS Research Compound

Siponimod CAS 1230487-00-9
Selective S1P1/S1P5 Receptor Modulator

An orally active, blood-brain-barrier penetrant second-generation sphingosine-1-phosphate receptor modulator (BAF-312, Mayzent) selective for S1P1 (EC50 0.39 nM) and S1P5 (EC50 0.98 nM), with >1000-fold selectivity over S1P2, S1P3 and S1P4. Siponimod sequesters lymphocytes in lymphoid tissue while engaging CNS-resident S1P receptors — the leading pharmacological tool for secondary progressive multiple sclerosis (SPMS), neuroinflammation and remyelination research.

S1P1 / S1P5 Modulator BBB Penetrant SPMS Research Lymphocyte Sequestration Remyelination BAF-312 / Mayzent Neuroinflammation
Request a Quote Technical Specs
516.60
MW (C29H35F3N2O3)
≥98%
Purity (HPLC)
0.39 nM
EC50 at S1P1

Molecular Information

Name: Siponimod
CAS: 1230487-00-9
Formula: C29H35F3N2O3
MW: 516.60 g/mol
Purity: ≥98% (HPLC)
SMILES: CCC1=C(C=CC(=C1)
  C(=NOCC2=CC(=C(C=C2)
  C3CCCCC3)C(F)(F)F)C)
  CN4CC(C4)C(=O)O
InChIKey: KIHYPELVXPAIDH
  -HNSNBQBZSA-N
MP: 154-157°C
Appearance: White to off-white powder
Solubility: DMSO; methanol (slight)
Synonyms: BAF-312 / Mayzent
Storage: -20°C, sealed, hygroscopic
🧪
CAS Number
1230487-00-9
⚖️
Molecular Weight
516.60
🎯
Primary Targets
S1P1 & S1P5
✅
Purity
≥98%

Siponimod Technical Specifications & QC Data

Complete physicochemical properties and quality control parameters for research-grade Siponimod powder (CAS 1230487-00-9, BAF-312)

📋 Physicochemical Properties

  • Product NameSiponimod
  • IUPAC Name1-({4-[(1E)-1-({[4-Cyclohexyl-3-(trifluoromethyl)phenyl]methoxy}imino)ethyl]-2-ethylphenyl}methyl)azetidine-3-carboxylic acid
  • CAS Number1230487-00-9
  • Code NamesBAF-312 / BAF312 / Mayzent
  • Molecular FormulaC29H35F3N2O3
  • Molecular Weight516.60 g/mol
  • Exact Mass516.259 Da
  • Geometry(1E)-oxime ether configuration
  • InChIKeyKIHYPELVXPAIDH-HNSNBQBZSA-N
  • AppearanceWhite to off-white solid powder
  • Melting Point154-157°C
  • Predicted pKa2.69 ± 0.20 (carboxylic acid)
  • Predicted Density1.24 ± 0.1 g/cm³
  • PubChem CID44599207
  • UNIIRR6P8L282I

🔬 Quality Control & Handling

  • Purity (HPLC)≥98%
  • Isomeric Purity(E)-oxime ≥98%; (Z)-isomer controlled
  • FormFree-flowing crystalline powder
  • ColorWhite to off-white
  • Storage Condition-20°C, sealed, dry, inert atmosphere
  • HygroscopicityHygroscopic — reseal promptly
  • SolubilityDMSO (recommended for stocks); methanol (slight); poorly water soluble
  • Related FormSiponimod hemifumarate (salt form)
  • QC DocumentationCOA / HPLC / NMR / MS / MSDS
  • Pack Sizes1g / 5g / 10g / 100g / 1KG
  • Stock StatusIn Stock
  • Use StatementResearch use only; not for human/clinical use

Receptor Selectivity Profile & Downstream Targets

Siponimod's defining property is receptor subtype discrimination: potent agonism at S1P1 and S1P5 with >1000-fold selectivity over the S1P2, S1P3 and S1P4 subtypes implicated in off-target cardiovascular and fibrotic effects

🎯 S1P1 (S1PR1) — EC50 0.39 nM 🧠 S1P5 (S1PR5) — EC50 0.98 nM ⬇️ S1P2 (Spared) ⬇️ S1P3 (Spared, >1000×) ⬇️ S1P4 (Spared) 🔄 S1P1 Internalization ⚡ GIRK Channel Activation 🧬 Gi/o Protein Coupling 🩸 Lymphocyte Egress Block 🧫 Oligodendrocyte S1P5 ⭐ Astrocyte S1P1 🛡️ Microglial Modulation

How Siponimod Works: Dual Peripheral and Central Mode of Action

A stepwise view of functional S1P1 antagonism, lymphocyte sequestration and direct CNS engagement in progressive multiple sclerosis models

1

High-Affinity S1P1/S1P5 Binding

Siponimod is a directly active modulator — unlike fingolimod it needs no sphingosine kinase 2 phosphorylation. It binds S1P1 and S1P5 with nanomolar potency while sparing S1P2, S1P3 and S1P4.

2

Receptor Internalization

Sustained agonism drives β-arrestin-mediated S1P1 internalization and degradation on lymphocytes (~91% internalization at 1 μM in 1 h), converting siponimod into a functional antagonist at the receptor.

3

Loss of S1P Gradient Sensing

Without surface S1P1, lymphocytes can no longer read the low-to-high S1P gradient between lymph node and blood that normally directs their exit — the core chemotactic switch of lymphocyte trafficking.

4

Lymphocyte Sequestration

Naive and central memory T cells are reversibly retained in secondary lymphoid organs. Peripheral blood lymphocyte counts fall within about six hours of the first dose and recover in most subjects within ~10 days of stopping.

5

Reduced CNS Immune Infiltration

Fewer autoreactive lymphocytes cross the blood-brain barrier, lowering demyelinating inflammatory activity — the basis for efficacy in experimental autoimmune encephalomyelitis (EAE) and in relapsing MS.

6

Direct CNS & Remyelination Effects

Because siponimod penetrates the CNS, it also engages astrocyte S1P1 and oligodendrocyte/OPC S1P5. Preclinical work reports reduced demyelination, preserved GABAergic interneurons, protection against synaptic neurodegeneration and enhanced remyelination.

Research Applications of Siponimod (BAF-312)

Where a CNS-penetrant, subtype-selective S1P modulator is the reference tool compound

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Secondary Progressive Multiple Sclerosis (SPMS)

The flagship application. Siponimod is the reference agent for studying compartmentalized CNS inflammation, confirmed disability progression, brain volume loss and cortical grey matter atrophy in progressive MS. The phase 3 EXPAND trial established reduced disability progression risk in active SPMS.

EXPAND Phase 3
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Sphingosine-1-Phosphate Signaling Biology

A benchmark chemical probe for dissecting S1P receptor subtype pharmacology — Gi/o coupling, β-arrestin recruitment, receptor internalization kinetics, GIRK channel activation and functional-antagonism versus agonism paradigms in transfected and primary cell systems.

GPCR Chemical Probe
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Remyelination & Oligodendrocyte Biology

Applied in cuprizone-induced demyelination, lysolecithin focal lesion and organotypic cerebellar slice models to evaluate OPC proliferation and differentiation, myelin basic protein expression, g-ratio morphometry and S1P5-dependent oligodendrocyte survival.

Myelin Repair
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Lymphocyte Trafficking & Immunology

Used to map lymphocyte egress, homing and recirculation. Standard readouts include flow-cytometric CD4/CD8 naive and central memory subset counts, lymph node retention imaging, S1P1 surface expression and dose-dependent peripheral lymphopenia kinetics.

Immune Trafficking
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Neuroinflammation & Glial Activation

Investigated for direct effects on microglial and astrocytic activation states, reactive astrogliosis, pro-inflammatory cytokine release and neurodegeneration-associated synaptic loss — key mechanisms of progression-independent-of-relapse-activity (PIRA) biology.

Glial Biology
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EAE & Autoimmune Disease Models

Effective in experimental autoimmune encephalomyelitis at prophylactic and therapeutic dosing (e.g. 0.3 mg/kg in mice), with clinical score, spinal cord infiltrate quantification and demyelination histology as primary endpoints. Also explored in colitis, uveitis and stroke models.

In Vivo Pharmacology
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Pharmacogenomics & CYP2C9 Research

A textbook example of genotype-guided dosing. Used in CYP2C9*1/*2/*3 phenotyping studies, recombinant CYP incubations, drug-drug interaction modeling with CYP2C9 and CYP3A4 inhibitors/inducers, and PBPK exposure simulations.

Pharmacogenomics
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Cardiac S1P Pharmacology

Used to study first-dose bradycardia mechanisms, S1P1-mediated GIRK channel activation in atrial myocytes, dose-titration mitigation strategies and species differences in cardiac S1P3 expression between rat, mouse and human.

Cardiac Safety
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Analytical Reference & DMPK

Supplied as an analytical reference standard for LC-MS/MS bioanalytical method validation, impurity and (Z)-isomer profiling, plasma protein binding, brain-to-plasma partition (Kp) determination and formulation development.

Reference Standard

Key Publications on Siponimod & S1P Receptor Modulation

Pivotal trials and mechanistic literature underpinning siponimod's use in multiple sclerosis research

Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. The Lancet. 2018;391(10127):1263-1273.
doi: 10.1016/S0140-6736(18)30475-6
Gergely P, Nuesslein-Hildesheim B, Guerini D, et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. British Journal of Pharmacology. 2012;167(5):1035-1047.
doi: 10.1111/j.1476-5381.2012.02061.x
Selmaj K, Li DKB, Hartung HP, et al. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. The Lancet Neurology. 2013;12(8):756-767.
doi: 10.1016/S1474-4422(13)70102-9
Behrangi N, Fischbach F, Kipp M. Mechanism of siponimod: anti-inflammatory and neuroprotective mode of action. Cells. 2019;8(1):24.
doi: 10.3390/cells8010024
Chun J, Hartung HP. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clinical Neuropharmacology. 2010;33(2):91-101.
doi: 10.1097/WNF.0b013e3181cbf825
Bigaud M, Guerini D, Billich A, Bassilana F, Brinkmann V. Second generation S1P pathway modulators: research strategies and clinical developments. Biochimica et Biophysica Acta. 2014;1841(5):745-758.
doi: 10.1016/j.bbalip.2013.11.001

Siponimod Pack Sizes & Ordering Information

Research-grade Siponimod powder (CAS 1230487-00-9) available in 1g / 5g / 10g / 100g / 1KG with full QC documentation and bulk custom synthesis support

TierPack SizeStock StatusSuitable ForLead Time & Shipping
Standard1 gIn StockS1P receptor binding and internalization assays, method developmentSame/next-day ship; ambient with ice pack
Medium5 gIn StockEAE and cuprizone rodent studies, dose-ranging pharmacologySame/next-day ship; express courier
Large10 gIn StockLong-term chronic dosing programs, multi-lab MS consortiaSame/next-day ship; DHL/FedEx/UPS
Bulk100 gIn StockFormulation and process development, toxicology batches, scale-upQuote to confirm; double-bagged HDPE drum, desiccant
Industrial1 KGMade to orderPilot/production scale, CMO supply, long-term supply agreementsScheduled batch delivery; palletized air/sea freight

💡 Reference sizes shown above; for exact siponimod bulk pricing and current availability please contact us for a quote. Bulk orders qualify for tiered discounts.

Siponimod FAQ — Frequently Asked Questions

What is Siponimod (CAS 1230487-00-9) and what is it used for?
Siponimod, development code BAF-312 and brand name Mayzent, is an orally active, CNS-penetrant, second-generation sphingosine-1-phosphate (S1P) receptor modulator selective for the S1P1 and S1P5 subtypes. Molecular formula C29H35F3N2O3, molecular weight 516.60 g/mol. It shows EC50 values of 0.39 nM at S1P1 and 0.98 nM at S1P5, with >1000-fold selectivity over S1P2, S1P3 and S1P4. In research it is the reference agent for secondary progressive multiple sclerosis, lymphocyte trafficking and remyelination studies.
How does Siponimod compare with fingolimod and ozanimod?
Fingolimod (FTY720) is a first-generation prodrug that must be phosphorylated by sphingosine kinase 2 and engages S1P1, S1P3, S1P4 and S1P5 — the S1P3 component is associated with cardiac and vascular effects. Siponimod and ozanimod are second-generation, directly active modulators that spare S1P3. Siponimod is the most extensively characterised for active secondary progressive MS, and its relatively short elimination half-life allows lymphocyte counts to normalise in about 10 days after stopping, versus roughly two months for fingolimod.
Why is Siponimod described as a "functional antagonist" if it is an agonist?
This is the central paradox of S1P pharmacology. Siponimod binds and activates S1P1, but the sustained agonism triggers β-arrestin recruitment, receptor internalization and lysosomal degradation — roughly 91% of S1P1 is internalized after 1 hour at 1 μM. With no surface receptor left, the lymphocyte becomes blind to the S1P gradient. The net cellular outcome is therefore functional antagonism even though the molecular event is agonism.
Why is Siponimod specifically studied in secondary progressive MS (SPMS)?
SPMS is driven less by acute peripheral immune relapses and more by compartmentalized CNS inflammation, chronic microglial activation, meningeal follicles and progressive neuroaxonal loss — biology that peripherally restricted immunomodulators struggle to reach. Siponimod's blood-brain barrier penetration plus S1P5 engagement on oligodendrocyte lineage cells provides a plausible dual peripheral/central mechanism. The EXPAND phase 3 trial (Kappos et al., Lancet 2018) reported a reduced risk of confirmed disability progression, and it became the first oral therapy approved for active SPMS in 2019.
What role does CYP2C9 metabolism play?
Siponimod is cleared primarily by CYP2C9 with a secondary contribution from CYP3A4. CYP2C9 is highly polymorphic: reduced-function alleles CYP2C9*2 and CYP2C9*3 markedly increase systemic exposure, so genotype-guided dose selection is used clinically and CYP2C9*3/*3 homozygotes are contraindicated. For pharmacology researchers this makes siponimod one of the best-documented case studies in pharmacogenomic dose individualization and a useful probe substrate in DDI and PBPK modeling.
How does S1P5 relate to remyelination and oligodendrocytes?
S1P5 (S1PR5) is expressed on mature oligodendrocytes, oligodendrocyte precursor cells (OPCs) and NK cells. Modulating S1P5 influences oligodendrocyte survival, process dynamics, differentiation and myelin sheath maintenance. Preclinical cuprizone demyelination and EAE studies have examined whether CNS-penetrant S1P1/S1P5 modulators reduce demyelination severity, promote remyelination, prevent synaptic neurodegeneration and protect GABAergic interneurons. Note that remyelination effects remain an active research question rather than a settled clinical claim.
Why does Siponimod cause transient bradycardia on first dose?
S1P1 activation in atrial myocytes opens G protein-coupled inwardly rectifying potassium (GIRK) channels, hyperpolarizing pacemaker cells and slowing heart rate and AV conduction. The maximum decline occurs within about 6 hours of the first dose and plateaus at higher doses; dose titration markedly reduces the incidence of AV block and sinus pauses. Interestingly the effect is species-dependent — pronounced in rats but not mice — reflecting differential cardiac S1P3 expression.
How should Siponimod powder be dissolved and stored?
Siponimod is soluble in DMSO (recommended for concentrated stocks) and slightly soluble in methanol; aqueous solubility is poor. Prepare a DMSO master stock, aliquot into single-use vials to avoid freeze-thaw cycles and store at -20°C or -80°C protected from light. Keep the final DMSO concentration ≤0.1% v/v in cell culture. The solid is hygroscopic — store sealed and dry at -20°C, ideally under inert atmosphere with desiccant, and allow vials to equilibrate to room temperature before opening to prevent condensation.
What is the difference between siponimod free acid and siponimod hemifumarate?
The free acid (CAS 1230487-00-9, C29H35F3N2O3, MW 516.60) is the active moiety and the form supplied here. Siponimod hemifumarate is the crystalline salt used in the commercial oral product to improve solid-state stability and manufacturability. Salt-form material has a different molecular weight, so dose and molar concentration calculations must be corrected for the counter-ion content when switching between forms.
What documentation and pack sizes do you supply?
Every lot ships with a Certificate of Analysis (COA) covering HPLC purity, 1H NMR confirmation, LC-MS identity, (E)/(Z)-oxime isomeric purity, water content and residual solvents; MSDS/SDS and Certificate of Origin are available on request. Catalog pack sizes are 1 g, 5 g, 10 g, 100 g and 1 KG — the first four tiers are in stock, the 1 KG industrial tier is made to order. Contact us for bulk quotes and custom quantities.

Need Siponimod (CAS 1230487-00-9) for Your Research?

Research-grade Siponimod / BAF-312 powder — purity ≥98% HPLC, COA included, 1g to 1KG
The reference selective S1P1/S1P5 modulator for SPMS, remyelination and neuroinflammation research — request a quote today

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Weight 1 g

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