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.
Click here for help
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: fingolimod

2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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
References
1. Cohen JA, Chun J. (2011)
Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis.
Ann Neurol, 69 (5): 759-77. [PMID:21520239]
2. Demont EH, Bailey JM, Bit RA, Brown JA, Campbell CA, Deeks N, Dowell SJ, Eldred C, Gaskin P, Gray JR et al.. (2016)
Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses.
J Med Chem, 59 (3): 1003-20. [PMID:26751273]
3. Forrest M, Sun SY, Hajdu R, Bergstrom J, Card D, Doherty G, Hale J, Keohane C, Meyers C, Milligan J et al.. (2004)
Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes.
J Pharmacol Exp Ther, 309 (2): 758-68. [PMID:14747617]
4. Hale JJ, Lynch CL, Neway W, Mills SG, Hajdu R, Keohane CA, Rosenbach MJ, Milligan JA, Shei GJ, Parent SA et al.. (2004)
A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists.
J Med Chem, 47 (27): 6662-5. [PMID:15615513]
5. Horga A, Montalban X. (2008)
FTY720 (fingolimod) for relapsing multiple sclerosis.
Expert Rev Neurother, 8 (5): 699-714. [PMID:18457527]
6. Koyrakh L, Roman MI, Brinkmann V, Wickman K. (2005)
The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I.
Am J Transplant, 5 (3): 529-36. [PMID:15707407]
7. Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C et al.. (2002)
Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.
Science, 296 (5566): 346-9. [PMID:11923495]
8. Qin X, Yue Z, Sun B, Yang W, Xie J, Ni E, Feng Y, Mahmood R, Zhang Y, Yue L. (2013)
Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels.
Br J Pharmacol, 168 (6): 1294-312. [PMID:23145923]
9. Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N et al.. (2004)
Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.
J Biol Chem, 279 (14): 13839-48. [PMID:14732717]