siponimod   Click here for help

GtoPdb Ligand ID: 9289

Synonyms: BAF-312 | BAF312 | compound 32 [PMID: 24900670] | Mayzent®
Approved drug PDB Ligand Immunopharmacology Ligand
siponimod is an approved drug (FDA (2019), EMA (2020))
Compound class: Synthetic organic
Comment: Pharmacologically, siponimod (BAF312) is a selective sphingosine-1-phosphate (S1P) receptor agonist, with some selectivity for the S1P1 and S1P5 receptor isoforms [8]. It is an orally active drug. Siponimod was developed by Novartis for secondary progressive multiple sclerosis (SPMS), originally as a back-up compound for fingolimod. Compared to fingolimod it has more favourable pharmacokinetics.
Novartis announced positive results from their Phase 3 EXPAND study (BAF312 versus placebo) in SPMS (August 2016- link to announcement here).
The SIPR signalling pathway is important in autoimmune biology.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 62.13
Molecular weight 516.26
XLogP 8
No. Lipinski's rules broken 1
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Canonical SMILES CCc1cc(ccc1CN1CC(C1)C(=O)O)C(=NOCc1ccc(c(c1)C(F)(F)F)C1CCCCC1)C
Isomeric SMILES CCc1cc(ccc1CN1CC(C1)C(=O)O)/C(=N/OCc1ccc(c(c1)C(F)(F)F)C1CCCCC1)/C
InChI 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+
Bioactivity Comments
Siponimod (BAF312) inhibits hERG by less than 10% at 25μM [8]. Screening against a panel of receptors, ion channels, transporters, and kinases suggests little potential for off-target effects.
Selectivity at GPCRs
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
S1P1 receptor Primary target of this compound Hs Agonist Agonist 9.4 – 10.1 pEC50 - 4,8-9
pEC50 10.1 (EC50 7.8x10-11 M) [9]
pEC50 9.4 (EC50 4x10-10 M) [4,8]
Description: In a GTPγS binding assay
S1P5 receptor Primary target of this compound Hs Agonist Agonist 9.0 pEC50 - 1,3,11
pEC50 9.0 (EC50 9.8x10-10 M) [1,3,11]
Description: In a GTPγS binding assay
S1P4 receptor Hs Agonist Agonist 6.1 pEC50 - 11
pEC50 6.1 (EC50 7.5x10-7 M) [11]
Description: In a GTPγS binding assay
S1P3 receptor Hs Agonist Agonist 5.3 pEC50 - 8
pEC50 5.3 (EC50 5x10-6 M) [8]
Description: In a GTPγS binding assay
Ligand mentioned in the following text fields