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.
|Cell lines||CHO cells|
|Preparation method||Agonist-mediated internalization of S1P1 receptors in CHO cells analysed by flow cytometry
Myc-tag hS1P1 cells were incubated for 1 h with agonist at 37°C in standard culture medium followed by a PBS wash. An aliquot was kept on ice for 3 h, while another aliquot was left for 3 (or 12) h in culture medium (no agonist) at 37°C. The cells were then incubated either with 4 µg·mL−1 monoclonal mouse anti C-myc IgG1 (Roche Applied Science, Mannheim, Germany) antibody or with isotype control mouse IgG1 (Pharmingen, BD Biosciences, Basel, Switzerland) for 60 min at 4°C, followed by an incubation with 1 µg·mL−1 of Alexa488-labelled goat anti-mouse secondary conjugates (Molecular Probes, Juro Supply, Luzern, Switzerland). The cells were subjected to flow cytometry measurements using 10000 viable cells per sample.
|Animal models||EAE model in the DA rat|
|Formulation||1% aqueous carboxy-methylcellulose (C-4888, Sigma Chemical Co, St Louis, MO)|
|Dosages||0.03, 0.3 and 3 mg/kg once daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
|Solubility||DMSO 10 mM|
The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.
Gergely P, et al. Br J Pharmacol. 2012 Nov;167(5):1035-47. PMID: 22646698.
|Related S1P Receptor Products|
Etrasimod (APD334) is a specific and orally available antagonist of the sphingosine-1-phosphate-1 (S1P1) receptor, with IC50 of 1.88 nM in CHO cells.
PF-543 Citrate is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC50 of 2 nM and a Ki of 3.6 nM.
Opaganib (ABC294640) is an orally bioavailable and selective sphingosine kinase-2 (SphK2) inhibitor with IC50 of approximately 60 μM.
NIBR-0213 is an orally active, potent and S1P1-selective sphingosine 1-phosphate (S1P) receptor antagonist.
A-971432 is an orally bioavailable, non-clastogenic, azetidinecarboxylate compound that acts as a highly potent and selective sphingosine-1-phosphate receptor 5 agonist (IC50 = 6 nM/S1P5, 362 nM/S1P1 and >10 μM/S1P3 in a radio-ligand binding assay).
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