Fingolimod

Identification

Summary

Fingolimod is a sphingosine 1-phosphate receptor modulator used to treat patients with the relapsing-remitting form of multiple sclerosis (MS) and studied to manage lung complications of COVID-19.

Brand Names
Gilenya
Generic Name
Fingolimod
DrugBank Accession Number
DB08868
Background

Multiple sclerosis or MS is a devastating inflammatory disease that often progresses and causes severe neurological, physical, and cognitive effects.3 Fingolimod is a sphingosine 1-phosphate receptor modulator for the treatment of relapsing-remitting multiple sclerosis. It was developed by Novartis and initially approved by the FDA in 2010.12

Fingolimod is currently being studied for the treatment of COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Phase 2 clinical trials are currently underway and completion is expected in July 2020.13

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 307.4708
Monoisotopic: 307.251129305
Chemical Formula
C19H33NO2
Synonyms
  • Fingolimod
  • Fingolimodum
External IDs
  • FTY-720A
  • FTY720

Pharmacology

Indication

Fingolimod is indicated for the treatment of patients aged 10 and above with relapsing forms of multiple sclerosis, which may include clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease.12

This drug is being studied for administration in patients infected with COVID-19 with a high risk for acute respiratory distress syndrome, or ARDS.13 As of April 3 2020, this is currently not an approved indication and clinical trials are underway.14

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

In multiple sclerosis, fingolimod binds to sphingosine receptors, reducing its associated neuroinflammation.12In COVID-19, it may reduce lung inflammation and improve the clinical outcomes of patients with this disease.13

Cardiovascular effects

Fingolimod causes a transient reduction in heart rate and AV conduction during treatment initiation. It has the potential to prolong the QT interval.13

Mechanism of action

Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system.10,11 S1P can be expressed ubiquitously, playing an important role in regulating inflammation. S1P1R, S1P2R, and S1P3R receptors can be found in the cardiovascular, immune, and central nervous systems. S1P4R is found on lymphocytic and hematopoietic cells, while S1P5R expression is found only on the spleen (on natural killer cells) or in the central nervous system.6

The active form of the drug, fingolimod phosphate, is a sphingosine 1-phosphate receptor modulator that exerts its mechanism of action in MS by binding to various sphingosine 1-phosphate receptors (1, 3, 4, and 5). It suppresses the exit of lymphocytes from lymph nodes, leading to a lower level of lymphocytes circulating in peripheral circulation. This reduces the inflammation that is associated with MS. The mechanism of action of fingolimod is not fully understood, but may be related to reduced lymphocyte circulation into the central nervous system.3,12

Immune modulating treatment such as fingolimod is not typically employed for SARS-CoV-2 pneumonia. Despite this, with the tissue findings of pulmonary edema and hyaline membrane formation, the timely use of immune modulators such as fingolimod can be considered to prevent acute respiratory distress syndrome (ARDS) associated with COVID-19. 13

TargetActionsOrganism
ASphingosine 1-phosphate receptor 5
modulator
Humans
UHistone deacetylase 1
inhibitor
Humans
ASphingosine 1-phosphate receptor 1
modulator
Humans
USphingosine 1-phosphate receptor 4
modulator
Humans
ASphingosine 1-phosphate receptor 3
modulator
Humans
Absorption

Fingolimod is slowly but efficiently absorbed in the gastrointestinal tract. AUC varies greatly, depending on the patient, and pharmacokinetic studies demonstrate a range of AUC values for fingolimod.5 The Tmax of fingolimod ranges between 12-16 hours and its bioavailability is 90-93%. Steady-state concentrations of fingolimod are achieved within 1-2 months after initiation when it is administered in a single daily dose.5,12

Volume of distribution

The volume of distribution of fingolimod is about 1200±260 L. It is approximately 86% distributed in the red blood cells (RBC).5,12

Protein binding

The protein binding of fingolimod and its active metabolite exceeds 99.7%.5,12

Metabolism

Sphingosine kinase metabolizes fingolimod to an active metabolite, fingolimod phosphate. Fingolimod metabolism occurs via 3 major metabolic pathways: firstly, phosphorylation of the (S)-enantiomer of fingolimod-phosphate (pharmacologically active), secondly, oxidation by cytochrome P450 4F2 (CYP4F2), and thirdly, fatty acid-like metabolism to various inactive metabolites. The formation of inactive non-polar ceramide analogs of fingolimod also occurs during its metabolism.5,12

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Route of elimination

About 81% of an oral dose of fingolimod is excreted in the urine in the form of inactive metabolites. Intact fingolimod and its active metabolite account for less than 2.5% of the dose, and can be found excreted in the feces.12

Half-life

The half-life of fingolimod and its active metabolite ranges from 6-9 days.5,12

Clearance

Fingolimod blood clearance is 6.3±2.3 L/h12, according to prescribing information. Another resource mentions it ranges from 6-8 L/h.5

Adverse Effects
Adverseeffects
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Toxicity

The LD50 of fingolimod in rats ranges from 300-600 mg/kg.7

Prescribing information for fingolimod does not mention symptoms or management of an overdose 12, however, a case report of an intentional overdose with 14mg of fingolimod and 2g phenoxymethylpenicillin resulted in hypotension in bradycardia, resolved by administering atropine.8 Since fingolimod has been associated with cardiotoxicity, it would be reasonable to expect cardiac effects such as bradycardia and heart block in the case of an overdose.9,12

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptAbatacept may increase the immunosuppressive activities of Fingolimod.
AcebutololAcebutolol may increase the bradycardic activities of Fingolimod.
AcetaminophenFingolimod may increase the hepatotoxic activities of Acetaminophen.
AdalimumabAdalimumab may increase the immunosuppressive activities of Fingolimod.
AdemetionineThe metabolism of Fingolimod can be decreased when combined with Ademetionine.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Fingolimod.
AjmalineFingolimod may increase the arrhythmogenic activities of Ajmaline.
AldesleukinAldesleukin may increase the immunosuppressive activities of Fingolimod.
AlefaceptAlefacept may increase the immunosuppressive activities of Fingolimod.
AlemtuzumabAlemtuzumab may increase the immunosuppressive activities of Fingolimod.
Interactions
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Food Interactions
  • Take with or without food.

Products

Products2
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Product Ingredients
IngredientUNIICASInChI Key
Fingolimod hydrochlorideG926EC510T162359-56-0SWZTYAVBMYWFGS-UHFFFAOYSA-N
International/Other Brands
Gilenia
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Asn-fingolimodCapsule0.5 mgOralAscend Laboratories LtdNot applicableNot applicableCanada flag
Fingolimod AccordCapsule0.5 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
Fingolimod AccordCapsule0.5 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
Fingolimod AccordCapsule0.5 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
Fingolimod AccordCapsule0.5 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
Fingolimod AccordCapsule0.5 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
Fingolimod AccordCapsule0.5 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
GilenyaCapsule0.5 mgOralNovartis Europharm Limited2016-09-20Not applicableEU flag
GilenyaCapsule0.25 mgOralNovartis Europharm Limited2020-12-16Not applicableEU flag
GilenyaCapsule0.5 mgOralNovartis Europharm Limited2016-09-20Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-fingolimodCapsule0.5 mgOralAccord Healthcare Inc2019-12-11Not applicableCanada flag
Apo-fingolimodCapsule0.5 mgOralApotex Corporation2019-11-01Not applicableCanada flag
FingolimodCapsule0.5 mg/1OralRising Pharmaceuticals, Inc.2021-01-01Not applicableUS flag
FingolimodCapsule0.5 mg/1OralBiocon Pharma Inc.2020-02-10Not applicableUS flag
Jamp FingolimodCapsule0.5 mgOralJamp Pharma Corporation2019-10-31Not applicableCanada flag
Mar-fingolimodCapsule0.5 mgOralMarcan Pharmaceuticals Inc2019-10-31Not applicableCanada flag
Mylan-fingolimodCapsule0.5 mgOralMylan Pharmaceuticals2019-09-25Not applicableCanada flag
PMS-fingolimodCapsule0.5 mgOralPharmascience Inc2019-08-30Not applicableCanada flag
Sandoz FingolimodCapsule0.5 mgOralSandoz Canada Incorporated2019-10-31Not applicableCanada flag
Taro-fingolimodCapsule0.5 mgOralTaro Pharmaceuticals, Inc.2019-10-24Not applicableCanada flag

Categories

ATC Codes
L04AA27 — Fingolimod
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Aralkylamines
Alternative Parents
Benzene and substituted derivatives / 1,2-aminoalcohols / Primary alcohols / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
1,2-aminoalcohol / Alcohol / Aralkylamine / Aromatic homomonocyclic compound / Benzenoid / Hydrocarbon derivative / Monocyclic benzene moiety / Organic oxygen compound / Organooxygen compound / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
primary amino compound, aminodiol (CHEBI:63115)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3QN8BYN5QF
CAS number
162359-55-9
InChI Key
KKGQTZUTZRNORY-UHFFFAOYSA-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
IUPAC Name
2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol
SMILES
CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1

References

Synthesis Reference

Ramesh Matioram Gidwani, Channaveerayya Hiremath, "PROCESS FOR PRODUCING FINGOLIMOD SALTS." U.S. Patent US20120184617, issued July 19, 2012.

US20120184617
General References
  1. An X, Kezuka T, Usui Y, Matsunaga Y, Matsuda R, Yamakawa N, Goto H: Suppression of experimental autoimmune optic neuritis by the novel agent fingolimod. J Neuroophthalmol. 2013 Jun;33(2):143-8. doi: 10.1097/WNO.0b013e31828ea2fc. [Article]
  2. Ali R, Nicholas RS, Muraro PA: Drugs in development for relapsing multiple sclerosis. Drugs. 2013 May;73(7):625-50. doi: 10.1007/s40265-013-0030-6. [Article]
  3. Ghasemi N, Razavi S, Nikzad E: Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017 Apr-Jun;19(1):1-10. Epub 2016 Dec 21. [Article]
  4. Fakhoury M, Negrulj R, Mooranian A, Al-Salami H: Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res. 2014 Jun 23;7:113-20. doi: 10.2147/JIR.S65979. eCollection 2014. [Article]
  5. David OJ, Kovarik JM, Schmouder RL: Clinical pharmacokinetics of fingolimod. Clin Pharmacokinet. 2012 Jan 1;51(1):15-28. doi: 10.2165/11596550-000000000-00000. [Article]
  6. Tran JQ, Hartung JP, Tompkins CA, Frohna PA: Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator. Clin Pharmacol Drug Dev. 2018 Aug;7(6):634-640. doi: 10.1002/cpdd.409. Epub 2017 Nov 10. [Article]
  7. Dumont FJ: Fingolimod. Mitsubishi Pharma/Novartis. IDrugs. 2005 Mar;8(3):236-53. [Article]
  8. Stephenson M, Wong A, Rotella JA, Crump N, Kerr F, Greene SL: Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine. J Med Toxicol. 2014 Jun;10(2):215-8. doi: 10.1007/s13181-013-0354-3. [Article]
  9. Enjeti AK, D'Crus A, Melville K, Verrills NM, Rowlings P: A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia. Anticancer Drugs. 2016 Jul;27(6):560-8. doi: 10.1097/CAD.0000000000000358. [Article]
  10. Tran JQ, Hartung JP, Peach RJ, Boehm MF, Rosen H, Smith H, Brooks JL, Timony GA, Olson AD, Gujrathi S, Frohna PA: Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator. J Clin Pharmacol. 2017 Aug;57(8):988-996. doi: 10.1002/jcph.887. Epub 2017 Apr 11. [Article]
  11. Chaudhry BZ, Cohen JA, Conway DS: Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis. Neurotherapeutics. 2017 Oct;14(4):859-873. doi: 10.1007/s13311-017-0565-4. [Article]
  12. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]
  13. Clinicaltrials.gov: Fingolimod in COVID-19 [Link]
  14. Clinical trials on drug repositioning for COVID-19 treatment [Link]
  15. European Medicines Agency Public Assessment Report: Gilenya (fingolimod) [Link]
KEGG Drug
D10001
PubChem Compound
107970
PubChem Substance
175427125
ChemSpider
97087
BindingDB
50158336
RxNav
1012892
ChEBI
63115
ChEMBL
CHEMBL314854
ZINC
ZINC000001542002
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fingolimod
MSDS
Download (351 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceAutonomic Nervous System Dysfunction / Multiple Sclerosis1
4CompletedBasic ScienceRelapsing Multiple Sclerosis (RMS)1
4CompletedBasic ScienceRelapsing Remitting Multiple Sclerosis (RRMS)3
4CompletedOtherMultiple Sclerosis1
4CompletedSupportive CareMultiple Sclerosis / Relapsing-Remitting1
4CompletedTreatmentMultiple Sclerosis2
4CompletedTreatmentMultiple Sclerosis, Relapsing Forms of Multiple Sclerosis1
4CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)6
4RecruitingTreatmentMultiple Sclerosis1
4RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral0.5 mg
CapsuleOral0.5 mg/1
CapsuleOral
CapsuleOral0.25 MG
CapsuleOral0.25 mg/1
CapsuleOral0.5 mg
Capsule, coatedOral0.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9187405Yes2015-11-172027-12-25US flag
US6004565No1999-12-212017-09-23US flag
US5604229Yes1997-02-182019-08-18US flag
US8324283Yes2012-12-042026-09-29US flag
US9592208Yes2017-03-142032-09-30US flag
US10543179No2007-12-252027-12-25US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)102-107https://www.chemicalbook.com/ChemicalProductProperty_US_CB4244536.aspx
boiling point (°C)479.5 https://www.lookchem.com/Fingolimod-hydrochloride/
water solubilitySolublehttps://www.chemicalbook.com/ChemicalProductProperty_US_CB4244536.aspx
logP5.5https://www.ema.europa.eu/en/documents/variation-report/gilenya-h-c-2202-ii-0034-epar-assessment-report-variation_en.pdf
pKa8.0https://www.ema.europa.eu/en/documents/variation-report/gilenya-h-c-2202-ii-0034-epar-assessment-report-variation_en.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0069 mg/mLALOGPS
logP4ALOGPS
logP4.06ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)14.41ChemAxon
pKa (Strongest Basic)9.38ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area66.48 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity93.28 m3·mol-1ChemAxon
Polarizability38.81 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9884
Blood Brain Barrier+0.5779
Caco-2 permeable-0.5055
P-glycoprotein substrateSubstrate0.6975
P-glycoprotein inhibitor INon-inhibitor0.9505
P-glycoprotein inhibitor IINon-inhibitor0.9391
Renal organic cation transporterNon-inhibitor0.823
CYP450 2C9 substrateNon-substrate0.8251
CYP450 2D6 substrateNon-substrate0.6702
CYP450 3A4 substrateNon-substrate0.7685
CYP450 1A2 substrateInhibitor0.5519
CYP450 2C9 inhibitorNon-inhibitor0.8526
CYP450 2D6 inhibitorInhibitor0.6567
CYP450 2C19 inhibitorNon-inhibitor0.8152
CYP450 3A4 inhibitorNon-inhibitor0.7348
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8945
Ames testNon AMES toxic0.8647
CarcinogenicityNon-carcinogens0.8562
BiodegradationNot ready biodegradable0.9062
Rat acute toxicity1.9996 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.933
hERG inhibition (predictor II)Non-inhibitor0.7302
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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insights and accelerate drug research.
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Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Sphingosine-1-phosphate receptor activity
Specific Function
Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both...
Gene Name
S1PR5
Uniprot ID
Q9H228
Uniprot Name
Sphingosine 1-phosphate receptor 5
Molecular Weight
41774.515 Da
References
  1. Zu Heringdorf DM, Ihlefeld K, Pfeilschifter J: Pharmacology of the sphingosine-1-phosphate signalling system. Handb Exp Pharmacol. 2013;(215):239-53. doi: 10.1007/978-3-7091-1368-4_13. [Article]
  2. Bhabak KP, Arenz C: Novel drugs targeting sphingolipid metabolism. Handb Exp Pharmacol. 2013;(215):187-96. doi: 10.1007/978-3-7091-1368-4_10. [Article]
  3. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcription regulatory region sequence-specific dna binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC1
Uniprot ID
Q13547
Uniprot Name
Histone deacetylase 1
Molecular Weight
55102.615 Da
References
  1. Hait NC, Wise LE, Allegood JC, O'Brien M, Avni D, Reeves TM, Knapp PE, Lu J, Luo C, Miles MF, Milstien S, Lichtman AH, Spiegel S: Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory. Nat Neurosci. 2014 Jul;17(7):971-80. doi: 10.1038/nn.3728. Epub 2014 May 25. [Article]
  2. Hait NC, Avni D, Yamada A, Nagahashi M, Aoyagi T, Aoki H, Dumur CI, Zelenko Z, Gallagher EJ, Leroith D, Milstien S, Takabe K, Spiegel S: The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERalpha expression and enhances hormonal therapy for breast cancer. Oncogenesis. 2015 Jun 8;4:e156. doi: 10.1038/oncsis.2015.16. [Article]
  3. Perla AS, Fratini L, Cardoso PS, de Farias CB, da Cunha Jaeger M, Roesler R: Fingolimod (FTY720) reduces viability and survival and increases histone H3 acetylation in medulloblastoma cells. Pediatr Hematol Oncol. 2020 Mar;37(2):170-175. doi: 10.1080/08880018.2019.1699213. Epub 2019 Dec 11. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Sphingosine-1-phosphate receptor activity
Specific Function
G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activatio...
Gene Name
S1PR1
Uniprot ID
P21453
Uniprot Name
Sphingosine 1-phosphate receptor 1
Molecular Weight
42810.195 Da
References
  1. David OJ, Kovarik JM, Schmouder RL: Clinical pharmacokinetics of fingolimod. Clin Pharmacokinet. 2012 Jan 1;51(1):15-28. doi: 10.2165/11596550-000000000-00000. [Article]
  2. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes.
Specific Function
G protein-coupled receptor activity
Gene Name
S1PR4
Uniprot ID
O95977
Uniprot Name
Sphingosine 1-phosphate receptor 4
Molecular Weight
41622.525 Da
References
  1. David OJ, Kovarik JM, Schmouder RL: Clinical pharmacokinetics of fingolimod. Clin Pharmacokinet. 2012 Jan 1;51(1):15-28. doi: 10.2165/11596550-000000000-00000. [Article]
  2. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.
Specific Function
G protein-coupled receptor activity
Gene Name
S1PR3
Uniprot ID
Q99500
Uniprot Name
Sphingosine 1-phosphate receptor 3
Molecular Weight
42249.805 Da
References
  1. David OJ, Kovarik JM, Schmouder RL: Clinical pharmacokinetics of fingolimod. Clin Pharmacokinet. 2012 Jan 1;51(1):15-28. doi: 10.2165/11596550-000000000-00000. [Article]
  2. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sphingosine-1-phosphate receptor activity
Specific Function
Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser...
Gene Name
SPHK1
Uniprot ID
Q9NYA1
Uniprot Name
Sphingosine kinase 1
Molecular Weight
42517.245 Da
References
  1. Pchejetski D, Bohler T, Brizuela L, Sauer L, Doumerc N, Golzio M, Salunkhe V, Teissie J, Malavaud B, Waxman J, Cuvillier O: FTY720 (fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1. Cancer Res. 2010 Nov 1;70(21):8651-61. doi: 10.1158/0008-5472.CAN-10-1388. Epub 2010 Oct 19. [Article]
  2. Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S: The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2. FEBS Lett. 2003 Nov 6;554(1-2):189-93. doi: 10.1016/s0014-5793(03)01168-2. [Article]
  3. Spijkers LJ, Alewijnse AE, Peters SL: FTY720 (fingolimod) increases vascular tone and blood pressure in spontaneously hypertensive rats via inhibition of sphingosine kinase. Br J Pharmacol. 2012 Jun;166(4):1411-8. doi: 10.1111/j.1476-5381.2012.01865.x. [Article]
  4. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Jin Y, Zollinger M, Borell H, Zimmerlin A, Patten CJ: CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8. doi: 10.1124/dmd.110.035378. Epub 2010 Nov 2. [Article]
  2. European Medicines Agency Public Assessment Report: Gilenya (fingolimod) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
Curator comments
Therapeutic doses of fingolimod are not expected to have significant induction effects on this enzyme.
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da
References
  1. Tanasescu R, Constantinescu CS: Pharmacokinetic evaluation of fingolimod for the treatment of multiple sclerosis. Expert Opin Drug Metab Toxicol. 2014 Apr;10(4):621-30. doi: 10.1517/17425255.2014.894019. Epub 2014 Mar 1. [Article]
  2. FDA Approved Products: Gilenya (fingolimod) oral capsules [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
There are limited data in the literature regarding this transporter action.
General Function
Sodium:dicarboxylate symporter activity
Specific Function
Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport ...
Gene Name
SLC1A2
Uniprot ID
P43004
Uniprot Name
Excitatory amino acid transporter 2
Molecular Weight
62103.665 Da
References
  1. Lee DH, Seubert S, Huhn K, Brecht L, Rotger C, Waschbisch A, Schlachetzki J, Klausmeyer A, Melms A, Wiese S, Winkler J, Linker RA: Fingolimod effects in neuroinflammation: Regulation of astroglial glutamate transporters? PLoS One. 2017 Mar 8;12(3):e0171552. doi: 10.1371/journal.pone.0171552. eCollection 2017. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
There are limited data in the literature regarding this transporter action.
General Function
Sodium:dicarboxylate symporter activity
Specific Function
Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport ...
Gene Name
SLC1A3
Uniprot ID
P43003
Uniprot Name
Excitatory amino acid transporter 1
Molecular Weight
59571.855 Da
References
  1. Lee DH, Seubert S, Huhn K, Brecht L, Rotger C, Waschbisch A, Schlachetzki J, Klausmeyer A, Melms A, Wiese S, Winkler J, Linker RA: Fingolimod effects in neuroinflammation: Regulation of astroglial glutamate transporters? PLoS One. 2017 Mar 8;12(3):e0171552. doi: 10.1371/journal.pone.0171552. eCollection 2017. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. di Nuzzo L, Orlando R, Nasca C, Nicoletti F: Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis. Drug Des Devel Ther. 2014 May 19;8:555-68. doi: 10.2147/DDDT.S52428. eCollection 2014. [Article]
  2. Xing Y, Wang ZH, Ma DH, Han Y: FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1. J Dig Dis. 2014 May;15(5):246-59. doi: 10.1111/1751-2980.12131. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Data regarding this transporter action are conflicting in the literature.
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Honig SM, Fu S, Mao X, Yopp A, Gunn MD, Randolph GJ, Bromberg JS: FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest. 2003 Mar;111(5):627-37. doi: 10.1172/JCI16200. [Article]
  2. Xing Y, Wang ZH, Ma DH, Han Y: FTY720 enhances chemosensitivity of colon cancer cells to doxorubicin and etoposide via the modulation of P-glycoprotein and multidrug resistance protein 1. J Dig Dis. 2014 May;15(5):246-59. doi: 10.1111/1751-2980.12131. [Article]

Drug created on April 28, 2013 20:17 / Updated on September 18, 2021 03:34