BAF312 (Siponimod)

Catalog No.S7179

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.

Price Stock Quantity  
USD 147 In stock
USD 397 In stock
USD 997 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

BAF312 (Siponimod) Chemical Structure

BAF312 (Siponimod) Chemical Structure
Molecular Weight: 516.6

Validation & Quality Control

Quality Control & MSDS

Product Information

  • Compare S1P Receptor Modulators
    Compare S1P Receptor Products
  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

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.
Targets S1P1 receptor [1] S1P5 receptor [1] S1P4 receptor [1] S1P3 receptor [1] S1P2 receptor [1]
IC50 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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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 Assay: [1]

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.

Animal Study: [1]

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

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Gergely P, et al. Br J Pharmacol, 2012, 167(5), 1035-1047.

[2] Pan S, et al. ACS Med, Chem, Lett, 2013, 4 (3), 333–337.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-06-25)

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 Recruiting 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

view more

Chemical Information

Download BAF312 (Siponimod) SDF
Molecular Weight (MW) 516.6
Formula

C29H35F3N2O3

CAS No. 1230487-00-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 100 mg/mL warming (193.57 mM)
Ethanol 44 mg/mL warming (85.17 mM)
Water <1 mg/mL (<1 mM)
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 Name (E)-1-(4-(1-(4-cyclohexyl-3-(trifluoromethyl)benzyloxyimino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related S1P Receptor Products

  • SB225002

    SB225002 is a potent, and selective CXCR2 antagonist with IC50 of 22 nM for inhibiting interleukin IL-8 binding to CXCR2, > 150-fold selectivity over the other 7-TMRs tested.

  • Smoothened Agonist (SAG) HCl

    Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.

  • SB-334867

    SB-334867 is a selective orexin-1 (OX1) receptor antagonist.

  • Fingolimod (FTY720) HCl

    Fingolimod (FTY720) HCl is a S1P antagonist with IC50 of 0.033 nM in K562, and NK cells.

  • PF-543

    PF-543, a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC50 and Ki of 2.0 nM and 3.6 nM, exhibits >100-fold selectivity over the SphK2 isoform.

    Features:The most potent inhibitor of SphK1 described to date.

  • SKI II

    SKI II is a highly selective and non ATP-competitive sphingosine kinase (SphK) inhibitor with IC50 of 0.5 μM, while exhibiting no inhibitory action on other kinases including PI3K, PKCα and ERK2.

  • Vismodegib (GDC-0449)

    Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM in a cell-free assay.

  • Forskolin

    Forskolin is a ubiquitous activator of eukaryotic adenylyl cyclase (AC) in a wide variety of cell types, commonly used to raise levels of cAMP in the study and research of cell physiology.

  • Cyclopamine

    Cyclopamine is a specific Hedgehog (Hh) signaling pathway antagonist of Smoothened (Smo) with IC50 of 46 nM in TM3Hh12 cells.

  • Plerixafor 8HCl (AMD3100 8HCl)

    Plerixafor 8HCl (AMD3100 8HCl) is the hydrochloride of Plerixafor, a chemokine receptor antagonist for CXCR4 and CXCL12-mediated chemotaxis with IC50 of 44 nM and 5.7 nM in cell-free assays, respectively.

Recently Viewed Items

Tags: buy BAF312 (Siponimod) | BAF312 (Siponimod) supplier | purchase BAF312 (Siponimod) | BAF312 (Siponimod) cost | BAF312 (Siponimod) manufacturer | order BAF312 (Siponimod) | BAF312 (Siponimod) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us