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
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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
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Summary of Clinical Use Click here for help
Used in the treatment of relapsing-remitting multiple sclerosis (MS) [5]. In May 2018, the FDA approved the use of fingolimod as a treatment for relapsing MS in pediatric patients. This is the first drug to be approved for treating MS in this patient group.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Fingolimod is metabolised to the active metabolite fingolimod phosphate by the enzyme sphingosine kinase. Fingolimod phosphate is a modulator of sphingosine receptors (S1P receptors), and its mechanism of action in the treatment of multiple sclerosis is derived from preventing the migration of lymphocytes into the central nervous system where they are implicated in autoimmune-driven demyelination associated with the disease. Clinical side effects (bradycardia, AV block, macular edema) are mostly (but not entirely) linked to S1P3R agonism [1,3,9]. Hence the development of S1P3R-sparing agonists such as compound 43 [PMID: 26751273] [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04280588 Fingolimod in COVID-19 Phase 2 Interventional First Affiliated Hospital of Fujian Medical University Fingolimod is being evaluated as a therapy for patients with severe SARS-CoV-2 pneumonia, as a method to prevent acute respiratory distress syndrome (ARDS) respiratory failure.
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