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.

COVID-19: Fingolimod has been evaluated in a small study of patients with moderate to severe COVID-19 (n=19), with mixed results [10]. Three days of treatment (in addition to standard interventions) did not reduce intubation or mortality rates, compared to placebo controls (n= 21), but it did signficantly reduce the re-admission rate.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: fingolimod

fingolimod is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
No information available.
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.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)