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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
Siponimod (BAF-312; WHO-9491; NVP-BAF-312; Mayzent) is a novel, potent and orally bioavailable S1P receptor modulator with immunomodulating activity. It can be used to treat medical conditions with significant immunopathology because of its high selectivity for S1P1 and S1P5 receptors (EC50 of 0.39 nM and 0.98 nM). It demonstrates selectivity over S1P2, S1P3, and S1P4 receptors that is >1000-fold. The metabolic clearance of BAF312 is high in rats, low to moderate in humans and monkeys, and low in dogs and mice, according to in vitro metabolism studies using liver microsomes.
Targets |
S1PR1 ( EC50 = 0.39 nM ); S1PR5 ( EC50 = 0.98 nM ); S1PR4 ( EC50 = 750 nM ); S1PR3 ( EC50 > 1000 nM ); S1PR2 ( EC50 > 10000 nM )
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
Centrifuging the cells at 26900 × g for 30 minutes at 4°C follows the homogenization of the cells. To re-suspend the membranes, mix 20 mM HEPES (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA, and 0.1% fat-free BSA at a protein concentration of 2-3 mg/mL. The membranes used in the GTPγ[35S] binding assay are 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 a wheat-germ agglutinin-coated scintillation proximity assay-bead, and 10 μM GDP for 10–15 min. With the addition of 200 pM GTPγ[35S], the GTPγ[35S]-binding reaction is initiate. Once the plates have been at room temperature for 120 minutes, they are centrifuged at 300 × g for 10 minutes and then tallied.
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Cell Assay |
Analysis of CHO cells using flow cytometry reveals antagonist-mediated internalization of S1P1 receptors. An agonist is added to standard culture medium and Myc-tag hS1P1 cells are incubated for 1 hour at 37°C. The cells are then washed with PBS. While one aliquot is left in culture medium (without an agonist) at 37°C for three hours, the other is kept on ice for three hours (or twelve hours). First, the cells are incubated for 60 minutes at 4°C with either 4 μg/mL monoclonal mouse anti-C-myc IgG1 antibody or isotype control mouse IgG1. Next, they are incubated with 1 μg/mL of goat anti-mouse secondary conjugates that have been labeled with Alexa488, which is a fluorescent dye. Using 10,000 viable cells per sample, the cells are measured using flow cytometry.
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Animal Protocol |
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References |
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Molecular Formula |
C29H35F3N2O3
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Molecular Weight |
516.6
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Exact Mass |
516.26
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Elemental Analysis |
C, 67.42; H, 6.83; F, 11.03; N, 5.42; O, 9.29
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CAS # |
1230487-00-9
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Appearance |
Solid powder
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SMILES |
CCC1=C(C=CC(=C1)/C(=N/OCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)/C)CN4CC(C4)C(=O)O
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InChi Key |
KIHYPELVXPAIDH-HNSNBQBZSA-N
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InChi Code |
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+
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Chemical Name |
1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid
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Synonyms |
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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 |
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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) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9357 mL | 9.6787 mL | 19.3573 mL | |
5 mM | 0.3871 mL | 1.9357 mL | 3.8715 mL | |
10 mM | 0.1936 mL | 0.9679 mL | 1.9357 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT05376579 | Active Recruiting |
Other: siponimod | Active Secondary Progressive Multiple Sclerosis |
Novartis Pharmaceuticals | June 17, 2022 | N/A |
NCT04933552 | Recruiting | Other: Siponimod | Multiple Sclerosis | Novartis Pharmaceuticals | December 15, 2021 | N/A |
NCT04926818 | Recruiting | Drug: Siponimod Drug: Ofatumumab |
Multiple Sclerosis (MS) | Novartis Pharmaceuticals | October 5, 2021 | Phase 3 |
NCT03623243 | Completed | Drug: Siponimod | Multiple Sclerosis Relapsing Multiple Sclerosis |
Novartis Pharmaceuticals | February 14, 2019 | Phase 3 |