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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
(S)-Ponesimod targets the sphingosine-1-phosphate receptor 1 (S1P1), a G protein-coupled receptor expressed on lymphocytes. Binding of (S)-ponesimod to S1P1 induces receptor internalization and degradation, effectively blocking the ability of lymphocytes to egress from lymph nodes in response to S1P gradients. This leads to peripheral lymphopenia and reduced immune cell infiltration into target tissues, providing therapeutic benefits in autoimmune diseases like multiple sclerosis. It is a potent and selective S1P1 modulator.
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| ln Vitro |
In vitro, (S)-ponesimod binds to human S1P1 with high affinity (Ki in the low nanomolar range). It induces S1P1 internalization in T lymphocyte cell lines at concentrations of 0.1-10 nM. Functional assays (GTPgammaS binding) show it is a potent agonist that leads to receptor desensitization. The compound also exhibits selective over S1P2, S1P3, S1P4, and S1P5 receptors at therapeutic concentrations. No significant cytotoxicity is observed in lymphocytes at effective concentrations. DMSO vehicle control (≤0.1%). Positive control: FTY720 (fingolimod phosphate).
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| ln Vivo |
In vivo, (S)-ponesimod induces a rapid and reversible reduction in peripheral blood lymphocyte counts in animal models (rats, mice) and humans. In experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis, oral administration of (S)-ponesimod (0.1-3 mg/kg) reduces disease severity and immune cell infiltration into the CNS. The compound is the active enantiomer of the racemic ponesimod, which has been approved for multiple sclerosis (marketed as Ponvory). For research use only.
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| Enzyme Assay |
For non-cellular S1P1 binding assay, membrane preparations from CHO cells expressing human S1P1 are used. Incubate membranes (10-20 ug) with 0.5 nM [3H]S1P and varying concentrations of (S)-ponesimod (0.001-1000 nM) in 50 mM HEPES pH 7.4, 5 mM MgCl2, 0.1% BSA, 1 mM DTT for 60 min at 25degC. Terminate by rapid filtration through GF/B filters. Wash, count filters. Non-specific binding with 1 uM unlabeled S1P. Calculate Ki. Positive control: FTY720-P. Negative control: DMSO.
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| Cell Assay |
For in vitro cell-based S1P1 internalization assay, culture CHO cells expressing human S1P1-GFP (green fluorescent protein) in DMEM with 10% FBS. Seed cells in 96-well plates (2×10⁴ cells/well). Treat with (S)-ponesimod at 0.001-1000 nM (0.1% DMSO) for 1-4 h at 37degC. Measure GFP fluorescence intensity by plate reader or confocal microscopy; internalization is seen as loss of membrane fluorescence. EC50 for internalization is calculated. For lymphocyte egress inhibition, isolate primary human T cells, treat with compound (0.1-100 nM) for 2 h, then perform transwell migration assay toward S1P (100 nM) in lower chamber. Count migrated cells. Positive control: FTY720-P (10 nM). Negative control: 0.1% DMSO. All experiments in triplicate.
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| Animal Protocol |
For in vivo pharmacodynamic study, male BALB/c mice (6-8 weeks, n=5/group) are treated with (S)-ponesimod orally by gavage at 0.1, 0.3, 1, 3 mg/kg formulated in 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween 80/45% saline. Control groups: vehicle, positive control (FTY720 1 mg/kg). Collect blood at 0, 2, 4, 6, 12, 24, 48 h post-dose. Perform complete blood count (CBC) to measure absolute lymphocyte count. (S)-ponesimod causes a dose-dependent reduction in circulating lymphocytes (up to 70-80% at 3 mg/kg). For EAE model, female C57BL/6 mice are immunized with MOG35-55 peptide/CFA. Treatment with (S)-ponesimod (0.3-3 mg/kg oral daily from day 7) reduces clinical scores and CNS inflammation. For research use only.
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| ADME/Pharmacokinetics |
(S)-Ponesimod has good oral bioavailability (F% ~60-80% in animals and humans). In humans, racemic ponesimod has Tmax of 2-4 h, terminal half-life (t½) of ~30-40 h, and is metabolized by CYP3A4. The (S)-enantiomer is the active form. Volume of distribution (Vd) is moderate (~100-200 L). Clearance (CL) is primarily hepatic. For storage, powder at -20degC for up to 3 years; in DMSO at -80degC for 1 year. Solubility: DMSO (10 mM). In vivo formulation: 10% DMSO/40% PEG300/5% Tween 80/45% saline or 0.5% methylcellulose.
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| Toxicity/Toxicokinetics |
In clinical studies, ponesimod (racemic) is generally well-tolerated. Common adverse events include bradycardia (dose-dependent), headache, elevated liver enzymes, and hypertension. The (S)-enantiomer is expected to have a similar profile. Preclinical studies show no significant toxicity at therapeutic doses (1-3 mg/kg). Standard laboratory safety precautions: avoid inhalation, ingestion, skin/eye contact; use PPE (gloves, lab coat); work in a fume hood. For research use only-not for human use.
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| Additional Infomation |
CAS: 854111-49-2. Molecular formula: C23H25ClN2O4S, molecular weight: 476.97. Also known as (S)-Ponesimod, Ponesimod active enantiomer. Appearance: solid powder. Purity: typically >98% by HPLC. Solubility: DMSO. Storage: -20degC. Target: S1P1. Research areas: multiple sclerosis, autoimmune diseases. Not for human use. For research only.
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| Molecular Formula |
C23H25CLN2O4S
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| Molecular Weight |
460.97
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| CAS # |
854111-49-2
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| Related CAS # |
(S)-Ponesimod
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| Appearance |
Off-white to yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1693 mL | 10.8467 mL | 21.6934 mL | |
| 5 mM | 0.4339 mL | 2.1693 mL | 4.3387 mL | |
| 10 mM | 0.2169 mL | 1.0847 mL | 2.1693 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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