Home GPCR & G Protein S1P Receptor agonist Siponimod (BAF312)

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Siponimod (BAF312) S1P Receptor agonist

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.
Siponimod (BAF312) S1P Receptor agonist Chemical Structure

Chemical Structure

Molecular Weight: 516.6

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Quality Control

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation 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
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Chemical Information, Storage & Stability

Molecular Weight 516.6 Formula

C29H35F3N2O3

 Storage (From the date of receipt)
CAS No. 1230487-00-9 Download SDF Storage of Stock Solutions

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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (193.57 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 25 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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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
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Mechanism of Action

Targets/IC50/Ki
S1P1 receptor [1]
0.39 nM(EC50)
S1P5 receptor [1]
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.[1] This compound (1 h at 1 μM) promotes prominent internalization of S1P1 receptors by 91%.[2]
Kinase Assay
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.
In vivo
Siponimod (BAF312) effectively suppresses encephalomyelitis (EAE) in rats by internalizing S1P1 receptors, rendering them insensitive to the egress signal from lymph nodes. [1] It significantly reduces clinical scores when dosed prophylactically or therapeutically in mice at 0.3 mg/kg. [3]
References

Applications

Methods Biomarkers Images PMID
Western blot p-ERK / ERK / p-AKT / AKT S7179-WB1 26856814
Immunofluorescence Vimentin / S1PR1 S7179-IF1 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

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