fingolimod   Click here for help

GtoPdb Ligand ID: 2407

Synonyms: FTY-720 | FTY720 | Gilenya®
Approved drug Immunopharmacology Ligand
fingolimod is an approved drug (FDA (2010), EMA (2011))
Compound class: Synthetic organic
Comment: Fingolimod was the first approved oral therapy for multiple sclerosis.
Fingolimod FTY720) is the prodrug of a S1P receptor agonist [4]. When fingolimod binds to S1P1R the complex is internalised and then degraded, so the drug acts as an indirect functional antagonist by preventing intracellular signalling. It acts as a lymphocyte migration inhibitor, promoting lymphocyte retention in lymphoid tissues, whilst preserving lymphocyte function [7]. Clinical efficacy results from modulation of S1P1 receptors. Adverse effects are thought to be caused by fingolimod's off-target effects on other S1P receptor subtypes.
Selective S1P1R agonists are being developed and investigated for immunomodulatory/immunosuppresant potential.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 12
Topological polar surface area 66.48
Molecular weight 307.25
XLogP 4.59
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES CCCCCCCCc1ccc(cc1)CCC(CO)(CO)N
Isomeric SMILES CCCCCCCCc1ccc(cc1)CCC(CO)(CO)N
InChI InChI=1S/C19H33NO2/c1-2-3-4-5-6-7-8-17-9-11-18(12-10-17)13-14-19(20,15-21)16-22/h9-12,21-22H,2-8,13-16,20H2,1H3
InChI Key KKGQTZUTZRNORY-UHFFFAOYSA-N
Bioactivity Comments
Note that most of the bioactivity maps to the active metabolite fingolimod-phosphate.
FTY720 exhibits no measurable agonist activity at human S1P2, S1P3 and S1P4 receptor subtypes, compared to S1P1 and S1P5 [4].
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 6.1 pIC50 - 4
pIC50 6.1 (IC50 8.4x10-7 M) [4]
S1P5 receptor Primary target of this compound Hs Agonist Agonist 5.7 pIC50 - 4
pIC50 5.7 (IC50 2.1x10-6 M) [4]
Selectivity at ion channels
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Kir3.4 Mm Activator Agonist - - 1x10-8 - 1x10-7 6
Conc range: 1x10-8 - 1x10-7 M [6]
Voltage: -90.0 mV
TRPM7 Mm Channel blocker Inhibition 6.1 pIC50 - 8
pIC50 6.1 (IC50 7.2x10-7 M) [8]
Voltage: -100.0 – 100.0 mV
Ligand mentioned in the following text fields