Fingolimod (FTY720) HCl

Alias: FTY720; Fingolimod HCl; FTY-720; FTY 720; Trade name: Gilenia and Gilenya.
Cat No.:V1502 Purity: ≥98%
Fingolimod HCl (formerly FTY-720; FTY 720; Gilenia and Gilenya), an FDA approved drug for the treatment of Multiple sclerosis, is a S1P (sphingosine 1-phosphate) antagonist with potential antineoplastic activity.
Fingolimod (FTY720) HCl Chemical Structure CAS No.: 162359-56-0
Product category: S1P Receptor
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of Fingolimod (FTY720) HCl:

  • Fingolimod (FTY-720)
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Fingolimod HCl (formerly FTY-720; FTY 720; Gilenia and Gilenya), an FDA approved drug for the treatment of Multiple sclerosis, is a S1P (sphingosine 1-phosphate) antagonist with potential antineoplastic activity. It reduces S1P in K562 and NK cells with an IC50 of 0.033 nM. Fungi is the source of this traditional remedy. In organ transplantation, fungolimod was initially discovered to be a therapeutic agent. Receptor-mediated effects on the immune system and central nervous system (CNS) are how it contributes to MS treatment. With its antineoplastic properties, fingolimod is used to treat multiple sclerosis.

Biological Activity I Assay Protocols (From Reference)
Targets
S1P ( IC50 = 0.033 nM )
ln Vitro

In vitro activity: The inhibitory effect of S1P is revered by various concentrations of FTY720, with IC50 effect of 173 nM. Furthermore, FTY720 (10 nM) by itself has no effect on co-stimulatory molecule expression. When S1P is compared to the combination of S1P and FTY720, the increased expression of HLA-I caused by S1P is reversed for both the percentages of cells and the MFI.[1] FTY720-P at medium and high doses also raises TGF-β1 levels. TGF-β1 and Foxp3 mRNA expression are upregulated in the high-dose FTY720-P group. In the medium and high-dose FTY720-P group, effector T cell proliferation is markedly suppressed at a 1:1 Treg/Teff cell ratio. The high-dose FTY720 group also experiences a 1:1 suppression of effector T cell proliferation.[2]

ln Vivo
FTY720 is effective in Ph+ but not Ph-ALL xenografts using an early disease model. In Ph+ ALL xenografts, FTY720 significantly lowers the disease burden by employing an early disease model. When treated promptly, Ph+ human ALL xenografts respond to FTY720 with an 80% reduction in total disease. When four distinct human Ph-ALL xenografts are used as controls, treatment with FTY720 does not, however, lead to a decrease in leukemia in mice. [3]
Cell Assay
Immature DCs are either left unaltered or incubated for four hours with 2 μM S1P, 10 nM FTY720, 10 nM SEW2871, or S1P combined with these medications. LPS at 1 μg/mL is used as a control. After being cleaned and placed in a 96-well plate with a v-bottom and 2 × 105 cells per well, the cells are once more washed and reconstituted in PBS buffer that contains 0.1% sodium azide. One microgram per milliliter of FITC-conjugated mouse anti-human CD80, one microgram per milliliter of FITC-conjugated mouse anti-human CD83, one microgram per milliliter of FITC-conjugated mouse anti-human CD86, one microgram per milliliter of FITC-conjugated mouse anti-human HLA-class I, one microgram per milliliter of FITC-conjugated mouse anti-human HLA-DR, one microgram per milliliter of FITC-conjugated mouse anti-human HLA-E, or one microgram per milliliter of FITC-conjugated mouse IgG are used as labels for them. After two rounds of washing, the cells are examined in a flow cytometer. Markers are set using FITC-conjugated mouse IgG as the isotype control. NK cells are either left untreated or incubated with 2 μM S1P for 4 hours, after which they are washed and stained with 1 μg/mL PE-conjugated mouse anti-human NKp30 (CD337), 1 μg/mL PE-conjugated mouse anti-human NKp44 (CD336), 1 μg/mL PE-conjugated mouse anti-human NKG2D (CD314), or as a control 1 μg/mL PE-conjugated mouse IgG1, for 45 minutes at 4 °C. To further stain NK cells, 1 μg/mL of FITC-conjugated anti-killer inhibitory receptor (KIR)/CD158 antibody is used. This antibody recognizes KIR2DL2, KIR2DL3, KIR2DS2, and KIR2DS4, and FITC-conjugated mouse IgG is used as a control. After two rounds of washing, the cells are examined in a flow cytometer. Markers are set in accordance with the isotype control mouse IgG that is conjugated with either PE or FITC.
Animal Protocol
Mice: Male C57BL/6J mice or sphingosine kinase-2 deficient (SPHK-2-/-) mice, weighing 25–30 g, are used in this study. They are fed a regular diet and given access to water whenever they want. Intraperitoneal injections of LPS (9 mg/kg), PepG (1 mg/kg), or their vehicle (0.9% saline) are given to C57BL/6J wild-type or SPHK-2-/-mice. Sham mice receive the same care as regular mice but are not given LPS or PepG. Mice are given Fingolimod hydrochloride (0.1 mg/kg i.v.) or its vehicle (10% DMSO) one hour after the LPS/PepG challenge. The selective PI3K inhibitor LY294002 (0.3 mg/kg i.v.) or the selective S1P2 receptor antagonist JTE 013 (1 mg/kg i.v.) or the selective S1P1 receptor agonist SEW2871 (1 mg/kg i.v.) or vehicle (10% DMSO) are given to mice 45 minutes after LPS/PepG and 15 minutes prior to Fingolimod hydrochloride in order to clarify the role of various S1P receptors in the observed effects of the drug.
Rat: The rats used are 200–250 g Sprague-Dawley rats. Fingolimod hydrochloride is applied icv (1 μg/2 μL), together with Kainic acid (KA), plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 days aftericv. The neuronal loss in the CA3 hippocampal region, the activation of microglia at the lesion site, and the neurological score are assessed in rats.
References

[1]. Cancer Immunol Immunother . 2010 Apr;59(4):575-86.

[2]. Int J Mol Med . 2012 Jul;30(1):211-9.

[3]. PLoS One . 2012;7(5):e36429.

[4]. Transpl Immunol . 2001 Feb;8(4):267-77

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C19H34CLNO2
Molecular Weight
343.9
Exact Mass
343.23
Elemental Analysis
C, 66.35; H, 9.96; Cl, 10.31; N, 4.07; O, 9.30
CAS #
162359-56-0
Related CAS #
Fingolimod; 162359-55-9
Appearance
Solid powder
SMILES
CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N.Cl
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
Chemical Name
2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol;hydrochloride
Synonyms
FTY720; Fingolimod HCl; FTY-720; FTY 720; Trade name: Gilenia and Gilenya.
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~69 mg/mL (~200.6 mM)
Water: N/A
Ethanol: 69~100 mg/mL (200.6~290.8 mM)
Solubility (In Vivo)
Saline: 20 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.9078 mL 14.5391 mL 29.0782 mL
5 mM 0.5816 mL 2.9078 mL 5.8156 mL
10 mM 0.2908 mL 1.4539 mL 2.9078 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04667949 Active
Recruiting
Drug: Fingolimod 0.5mg Relapsing Multiple Sclerosis
(RMS)
Novartis Pharmaceuticals February 20, 2021 Phase 4
NCT04088630 Active
Recruiting
Drug: Fingolimod 0.5 mg
Drug: Placebo
Cerebral Edema
Stroke Hemorrhagic
Wake Forest University
Health Sciences
August 7, 2020 Early Phase 1
NCT05423769 Active
Recruiting
Drug: Fingolimod Relapsing-Remitting
Multiple Sclerosis
Hikma Pharmaceuticals LLC January 19, 2022 N/A
NCT04480853 Recruiting Drug: Fingolimod Multiple Sclerosis Novartis Pharmaceuticals October 12, 2020 Phase 4
NCT01285479 Completed Drug: Fingolimod Multiple Sclerosis Novartis Pharmaceuticals October 15, 2011 N/A
Biological Data
  • Fingolimod (FTY720) HCl

    FTY720 does not reduce disease burden in a xenograft model of advanced human ALL. PLoS One. 2012;7(5):e36429.
  • Fingolimod (FTY720) HCl

    FTY720 does not reduce Ph− ALL in a μodel of early disease. PLoS One. 2012;7(5):e36429.
  • Fingolimod (FTY720) HCl

    FTY720 reactivates PP2A but induces PP2A-independent cell death. PLoS One. 2012;7(5):e36429.
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