WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100355
CAS#: 162359-56-0 (HCl)
Description: Fingolimod, also known as FTY720, is an immunosuppressive drug. It is derived from the myriocin (ISP-1) metabolite of the fungus Isaria sinclairii. It is a structural analogue of sphingosine and gets phosphorylated by sphingosine kinases in the cell (most importantly sphingosine kinase. The molecular biology of phospho-fingolimod is thought to lie in its activity at one of the five sphingosine-1-phosphate receptors, S1PR1.
MedKoo Cat#: 100355
Name: Fingolimod HCl
CAS#: 162359-56-0 (HCl)
Chemical Formula: C19H34ClNO2
Molecular Weight: 343.94
Elemental Analysis: C, 66.35; H, 9.96; Cl, 10.31; N, 4.07; O, 9.30
Related CAS #: 162359-56-0 (HCl) 162359-55-9 (free base)
Synonym: FTY720; FTY-720; FTY 720. Fingolimod; Fingolimod HCl; Band name: Gilenia and Gilenya.
IUPAC/Chemical Name: 2-amino-2-(4-octylphenethyl)propane-1,3-diol hydrochloride.
InChi Key: SWZTYAVBMYWFGS-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H33NO2.ClH/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;1H
SMILES Code: OCC(CCC1=CC=C(CCCCCCCC)C=C1)(N)CO.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Fingolimod hydrochloride (FTY720) is a sphingosine 1-phosphate (S1P) receptors modulator.|
|In vitro activity:||FTY720 decreased glioma cell viability in a dose-dependent manner in U251MG, U87MG, and U118MG (Figure 1a). Interestingly, although the pan-caspase inhibitor (z-VAD) completely blocked TNF-α plus cycloheximide (CHX)-induced cell death, z-VAD had no effect on cell death in FTY720-treated glioma cells (Figure 1b). Next, the possibility of necrosis was examined. When cells were treated with NecroX-5, a necrosis inhibitor, cell death by H2O2 was blocked, but FTY720-induced cell death did not change (Figure 1f). Therefore, these data indicate that FTY720 induces non-apoptotic and non-necrotic cell death in glioma cells. Reference: Cancers (Basel). 2020 Nov; 12(11): 3388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696845/|
|In vivo activity:||Compared with the sham mice group, the expressions of occludin and claudin-5 in the TBI group and the TBI + vehicle group were significantly decreased (p < 0.05), and both of them were significantly increased after FTY720 treatment (Fig. 3A, C, D). Immunofluorescent staining also showed that occludin and claudin-5 were down-regulated after TBI significantly and which were restored by FTY720 (Fig. 3E, F, G). Besides, activated (phosphorylated) ERK1/2, a key protein that transmits signals from surface receptors to the nucleus, was significantly elevated in the brain at 24 h after TBI. And this increase was reduced after treatment with FTY720 (p < 0.05) (Fig. 3A, B). Then the expression of the target of FTY720 was tested, and the result found that the expression of S1PR1 decreased significantly after using FTY720 (p < 0.05) (Supplementary Fig. C, D). But FTY720 had no effect on the content of S1P after TBI (p > 0.05) (Supplementary Fig. B). Reference: Int J Med Sci. 2021; 18(2): 304–313. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757143/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|Ethanol:PBS (pH 7.2) (1:1)||0.2||0.58|
The following data is based on the product molecular weight 343.94 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Min KJ, Kwon TK. Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells. Cancers (Basel). 2020 Nov 16;12(11):3388. doi: 10.3390/cancers12113388. PMID: 33207629; PMCID: PMC7696845. 2. Chang WT, Liu PY, Wu SN. Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes. Molecules. 2020 Oct 2;25(19):4525. doi: 10.3390/molecules25194525. PMID: 33023219; PMCID: PMC7582672. 3. Zhu C, Wen S, Li J, Meng H, Zhang J, Zhao K, Wang L, Zhang Y. FTY720 Inhibits the Development of Collagen-Induced Arthritis in Mice by Suppressing the Recruitment of CD4+ T Lymphocytes. Drug Des Devel Ther. 2021 May 11;15:1981-1992. doi: 10.2147/DDDT.S293876. PMID: 34007158; PMCID: PMC8123953. 4. Cheng H, Di G, Gao CC, He G, Wang X, Han YL, Sun LA, Zhou ML, Jiang X. FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury. Int J Med Sci. 2021 Jan 1;18(2):304-313. doi: 10.7150/ijms.49066. PMID: 33390799; PMCID: PMC7757143.|
|In vitro protocol:||1. Min KJ, Kwon TK. Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells. Cancers (Basel). 2020 Nov 16;12(11):3388. doi: 10.3390/cancers12113388. PMID: 33207629; PMCID: PMC7696845. 2. Chang WT, Liu PY, Wu SN. Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes. Molecules. 2020 Oct 2;25(19):4525. doi: 10.3390/molecules25194525. PMID: 33023219; PMCID: PMC7582672.|
|In vivo protocol:||1. Zhu C, Wen S, Li J, Meng H, Zhang J, Zhao K, Wang L, Zhang Y. FTY720 Inhibits the Development of Collagen-Induced Arthritis in Mice by Suppressing the Recruitment of CD4+ T Lymphocytes. Drug Des Devel Ther. 2021 May 11;15:1981-1992. doi: 10.2147/DDDT.S293876. PMID: 34007158; PMCID: PMC8123953. 2. Cheng H, Di G, Gao CC, He G, Wang X, Han YL, Sun LA, Zhou ML, Jiang X. FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury. Int J Med Sci. 2021 Jan 1;18(2):304-313. doi: 10.7150/ijms.49066. PMID: 33390799; PMCID: PMC7757143.|
1: Brunkhorst R, Vutukuri R, Pfeilschifter W. Fingolimod for the treatment of neurological diseases-state of play and future perspectives. Front Cell Neurosci. 2014 Sep 12;8:283. doi: 10.3389/fncel.2014.00283. eCollection 2014. Review. PubMed PMID: 25309325; PubMed Central PMCID: PMC4162362.
2: Harrison K. Fingolimod for multiple sclerosis: a review for the specialist nurse. Br J Nurs. 2014 Jun 12-25;23(11):582-9. Review. PubMed PMID: 24933548.
3: Thomas K, Ziemssen T. Management of fingolimod in clinical practice. Clin Neurol Neurosurg. 2013 Dec;115 Suppl 1:S60-4. doi: 10.1016/j.clineuro.2013.09.023. Review. PubMed PMID: 24321158.
4: Pilz G, Harrer A, Wipfler P, Oppermann K, Sellner J, Fazekas F, Trinka E, Kraus J. Tumefactive MS lesions under fingolimod: a case report and literature review. Neurology. 2013 Nov 5;81(19):1654-8. doi: 10.1212/01.wnl.0000435293.34351.11. Epub 2013 Oct 4. Review. Erratum in: Neurology. 2014 Apr 29;82(17):1569. PubMed PMID: 24097813.
5: Singer BA. Fingolimod for the treatment of relapsing multiple sclerosis. Expert Rev Neurother. 2013 Jun;13(6):589-602. doi: 10.1586/ern.13.52. Review. PubMed PMID: 23738997.
6: Willis MA, Cohen JA. Fingolimod therapy for multiple sclerosis. Semin Neurol. 2013 Feb;33(1):37-44. doi: 10.1055/s-0033-1343794. Epub 2013 May 25. Review. PubMed PMID: 23709211.
7: Groves A, Kihara Y, Chun J. Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy. J Neurol Sci. 2013 May 15;328(1-2):9-18. doi: 10.1016/j.jns.2013.02.011. Epub 2013 Mar 19. Review. PubMed PMID: 23518370; PubMed Central PMCID: PMC3640626.
8: SzÃ©plaki G, Merkely B. [Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis]. Ideggyogy Sz. 2012 Nov 30;65(11-12):369-76. Review. Hungarian. PubMed PMID: 23289171.
9: Nikitin AV. [Molecular and cellular mechanisms of fingolimod action]. Antibiot Khimioter. 2013;58(11-12):38-42. Review. Russian. PubMed PMID: 24734428.
10: Liu J, Zhang C, Tao W, Liu M. Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke. Int J Neurosci. 2013 Mar;123(3):163-9. doi: 10.3109/00207454.2012.749255. Epub 2012 Dec 21. Review. PubMed PMID: 23167788.
Status of FDA approval
June 11, 2010 Â— The US Food and Drug Administration's (FDA's) Peripheral and Central Nervous System Drugs Advisory Committee has recommended approval for the novel oral agent fingolimod in the treatment of patients with relapsing-remitting multiple sclerosis (MS). The highly anticipated drug is the first in a new class of disease-modifying agents called sphingosine 1 phosphate receptor modulators. Fingolimod's sponsor, Novartis, was seeking a new drug application for patients with MS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. Novartis plans to market fingolimod as Gilena. If approved by the FDA, it will be the first oral agent for patients with MS, giving them a welcome alternative to currently available injectable therapies. The committee spent hours discussing a long list of questions posed by the FDA but was unanimous in its decision to recommend fingolimod's approval.
History of research and development
First synthesized in 1992, fingolimod was derived from an immunosuppressive natural product, myriocin (ISP-I) through chemical modification. Myriocin was isolated from the culture broth a type of vegetative wasp (Isaria sinclairii) that was an eternal youth nostrum in traditional Chinese medicine. Showing postive results in both in vitro (mixed lymphocyte reaction) and in vivo screening (prolonging rat skin graft survival time), myriocin was modified through a series of steps to yield fingolimod, code named at the time FTY720. Structure activity relationship (SAR) studies on myriocin homologs and partially synthetic derivatives showed that the configuration at the carbon bearing the 3-hydroxy group or the 14-ketone, the 6-double bond, and the 4-hydroxy group were not important for its activity and simplification of the structure of ISP-I was done in an attempt to reduce toxicity and improve drugability. Elimination of side chain functionalities and removal of chiral centers was part of the simplification process and an intermediate compound (ISP-I-28) with the carboxylic acid of myriocin transformed to a hydroxymethyl group was generated. ISP-I-28 was found to be less toxic and more effective at lenghtening rat skin allograft time than ISP-1. (source: http://en.wikipedia.org/wiki/Fingolimod).
1. Organ transplant: in a previous phase III clinical trial of kidney transplantation, fingolimod was found to be no better than the existing standard of care.
2. Multiple sclerosis: in two Phase III clinical trials, fingolimod reduced the rate of relapses in relapsing-remitting multiple sclerosis by over half compared both to placebo and to the active comparator interferon beta-1-a. A double-blind randomized control trial comparing fingolimod to placebo found the drug reduced the annualized frequency of relapses to 0.18 relapses per year at 0.5 mg/day or 0.16 relapses per year at 1.25 mg/day, compared to 0.40 relapses per year for those patients taking the placebo. The probability of disease progression at 24 month followup was lower in the fingolimod groups compared to placebo (hazard ratio 0.70 at 0.5 mg and 0.68 at 1.25 mg). Fingolimod patients also had better results according to MRI imaging of new or enlarged lesions at 24 month followup. Side effects leading to discontinuation of the study drug were more common in the higher dose group (14.2% of patients) than at the lower dose (7.5%) or placebo (7.7%). Serious adverse events in the fingolimod group included bradycardia, relapse, and basal-cell carcinoma. Seven episodes of bradycardia occurred during the monitoring period after administration of the first dose, and were asymptomatic in six of these cases. There was a higher rate of lower respiratory tract infections (including bronchitis and pneumonia) in the fingolimod groups (9.6% at 0.5 mg, 11.4% at 1.5 mg) than the placebo group (6.0%). Other adverse events reported on the study drug included macular edema, malignant neoplasms, and laboratory abnormalities.
Develope r of the product: Novartis.