research use only

Siponimod (BAF312) S1P Receptor agonist

Name: Siponimod (BAF312)
Brand: Selleck Chemicals
SKU: S7179
Availability: InStock
Rating: 5 (15 reviews)

Cat.No.S7179

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

Chemical Structure

Molecular Weight: 516.6

Jump to

Quality Control

Batch: Purity: 99.96%

99.96

Related Targets	K-Ras CXCR Hedgehog/Smoothened PKA Adrenergic Receptor AChR 5-HT Receptor Histamine Receptor Dopamine Receptor Ras
Other S1P Receptor Inhibitors	JTE 013 PF 429242 SEW 2871 Etrasimod(APD334) MP-A08 SLF1081851 hydrochloride K145 CAY10444 CYM5541 Sphingosine-1-phosphate

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
CHO	Function assay	120 mins	Agonist activity at human S1P1 receptor transfected in CHO cells incubated for 10 to 15 mins prior to GTPgamma35S addition measured after 120 mins by GTPgamma35S binding assay, EC50=0.0004μM	24900670
CHO	Function assay		Agonist activity at human S1P5 receptor expressed in CHO cells by [35S]GTPgammaS binding assay, EC50=0.00098μM	24125884
CHO	Function assay		Agonist activity at human S1P4 receptor expressed in CHO cells by [35S]GTPgammaS binding assay, EC50=0.75μM	24125884
CHO	Function assay	120 mins	Agonist activity at human S1P3 receptor transfected in CHO cells incubated for 10 to 15 mins prior to GTPgamma35S addition measured after 120 mins by GTPgamma35S binding assay, EC50=5μM	24900670
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (193.57 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 25 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	516.6	Formula	C₂₉H₃₅F₃N₂O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1230487-00-9	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CCC1=C(C=CC(=C1)C(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O

Mechanism of Action

Targets/IC₅₀/Ki	S1P1 receptor 0.39 nM(EC50) S1P5 receptor 0.98 nM(EC50)
In vitro	Siponimod (BAF312) is a potent and selective S1P receptor agonist, exhibiting EC50 values of 0.39 nM and 0.98 nM for S1P₁ and S1P₅ receptors, with >1000-fold selectivity over S1P₂, S1P₃, and S1P₄ receptors. This compound (1 h at 1 μM) promotes prominent internalization of S1P1 receptors by 91%.
Kinase Assay	GTPγ[³⁵S] binding assay
Kinase 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.
In vivo	Siponimod (BAF312) effectively suppresses encephalomyelitis (EAE) in rats by internalizing S1P₁ receptors, rendering them insensitive to the egress signal from lymph nodes. It significantly reduces clinical scores when dosed prophylactically or therapeutically in mice at 0.3 mg/kg.
References	[1] https://pubmed.ncbi.nlm.nih.gov/22646698/ [2] http://pubs.acs.org/doi/full/10.1021/jm200609t [3] https://pubmed.ncbi.nlm.nih.gov/23436932/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-ERK / ERK / p-AKT / AKT		26856814
Immunofluorescence	Vimentin / S1PR1		26856814

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05376579	Active not recruiting	Active Secondary Progressive Multiple Sclerosis	Novartis Pharmaceuticals\|Novartis	June 17 2022	--
NCT04895202	Terminated	Secondary Progressive Multiple Sclerosis With Inflammatory Disease Activity	Novartis Pharmaceuticals\|Novartis	November 19 2021	--
NCT05826028	Completed	Secondary Progressive Multiple Sclerosis	Novartis Pharmaceuticals\|Novartis	July 9 2020	--
NCT02029274	Terminated	Active Dermatomyositis	Novartis Pharmaceuticals\|Novartis	August 25 2013	Phase 2

Tech Support

Handling Instructions

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

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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):