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| 5mg |
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Purity: =99.87%
Fingolimod phosphate (FTY-720-P) is the phosphate salt of Fingolimod (FTY-720; FTY 720; Gilenia and Gilenya) with improved water solubility. Fingolimod is an FDA approved drug for the treatment of Multiple sclerosis, acting as a S1P (sphingosine 1-phosphate) antagonist with potential antineoplastic activity. It inhibits S1P with an IC50 of 0.033 nM in K562 and NK cells. It is a folk medicine emerged from Fungi. Fingolimod was firstly found to be a therapeutic agent in organ transplantation. It plays the role in MS treatment through receptor-mediated actions both on the immune system and in the CNS. Fingolimod is used to treat multiple sclerosis, and has antineoplastic activity.
Fingolimod phosphate (FTY720) is a sphingosine 1-phosphate (S1P) receptor agonist used as an oral drug for relapsing-remitting multiple sclerosis (MS). FTY720 is the phosphorylated form of fingolimod. Its primary known mechanism is to prevent lymphocyte egress from lymphoid organs, thereby inhibiting autoreactive lymphocyte infiltration into the central nervous system (CNS). This study investigated whether FTY720 directly affects microglia, the innate immune cells of the CNS. The results showed that FTY720 binds to S1P receptors on microglia, downregulating their production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulating their production of neurotrophic factors (BDNF, GDNF), suggesting direct neuroprotective effects on microglia. [1]| Targets |
sphingosine 1-phosphate (S1P)(IC50 = 0.033 nM, in K562 and NK cells); PAK1
Sphingosine 1-phosphate receptor 1 (S1P1): FTY720 binds to S1P1 on microglia. Blocking S1P1 with the antagonist W146 (250 nM) significantly reduced the suppressive effect of FTY720 on microglial TNF-α production. FTY720 binds all S1P receptor subtypes except S1P2. [1] |
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| ln Vitro |
Fingolimod phosphate stops autoreactive lymphocytes from entering the central nervous system and stops lymphocytes from leaving lymphoid organs [1]. Fingolimod phosphate (0, 1, 10, 100 nM) binds to the S1P1 receptor and inhibits activated microglia's production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-a[1]. Additionally, microglia produce more brain-derived neurotrophic factor and glial cell-derived neurotrophic factor when exposed to (0, 1, 10, 100 nM) [1].
- S1P Receptor Expression in Microglia: Mouse primary microglia expressed all S1P receptor subtypes (S1P1, S1P2, S1P3, S1P4, S1P5), with the highest expression levels observed for S1P1. Stimulation with LPS (1 μg/ml) significantly reduced microglial expression levels of S1P2, S1P4, and S1P5. [1] - Inhibition of Pro-inflammatory Cytokine Production: LPS (1 μg/ml) enhanced microglial production of TNF-α, IL-1β, and IL-6. FTY720 (1-100 nM) reduced these effects in a dose-dependent manner. At 100 nM, FTY720 significantly decreased TNF-α, IL-1β, and IL-6 production as measured by ELISA and RT-PCR. The suppressive effect on TNF-α was significantly reduced by the S1P1 antagonist W146 (250 nM), but not by the S1P3/S1P5 antagonist suramin (10 μM) or the S1P4 antagonist CYM50358 (100 nM). [1] - Upregulation of Neurotrophic Factor Production: LPS (1 μg/ml) increased microglial expression of BDNF and GDNF. FTY720 (1-100 nM) enhanced these effects in a dose-dependent manner, as shown by RT-PCR (12h) and Western blotting (48h). At 100 nM, FTY720 significantly increased BDNF and GDNF protein levels. [1] |
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| ln Vivo |
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| Cell Assay |
- Primary Microglia Culture: Mouse primary microglia were isolated from newborn C57BL/6 mice (day 14 in vitro) using the "shaking off" method. Cells were maintained in DMEM with 10% fetal calf serum, 5 μg/ml bovine insulin, and 0.2% glucose. Purity was 97-100% by Fc receptor immunostaining. [1]
- RT-PCR: Microglia were collected 12 hours after LPS stimulation. Total RNA was extracted, and first-strand cDNA was synthesized. RT-PCR was performed to amplify transcripts for S1P1-S1P5, TNF-α, IL-1β, IL-6, BDNF, GDNF, and GAPDH using specific oligonucleotide primers. [1] - Flow Cytometry: Microglia were collected 24 hours after LPS stimulation. Cells were fixed with 4% paraformaldehyde and stained with anti-S1P1, anti-S1P2, anti-S1P3, anti-S1P4, and anti-S1P5 rabbit polyclonal antibodies, followed by Alexa Fluor 488-conjugated anti-rabbit IgG. Samples were analyzed on a flow cytometer. [1] - ELISA: Microglia were collected 24 hours after LPS stimulation. Microglial production of IL-1β, IL-6, and TNF-α was assessed with specific ELISA kits according to the manufacturers' protocols. [1] - Western Blotting: Microglia were collected 48 hours after LPS stimulation. Cells were lysed in TNE buffer with protease inhibitors. 20 μg of protein from total cell lysates were separated on a 4-20% Tris-glycine SDS-polyacrylamide gradient gel, transferred to a PVDF membrane, and probed with anti-BDNF, anti-GDNF, or anti-β-actin antibodies. Signals were visualized using enhanced chemiluminescence. [1] |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
- Brain Penetration: FTY720 can penetrate the blood-brain barrier. [1]
- Cerebrospinal Fluid Concentration: The effective concentrations of FTY720 used in this study (1-100 nM) were approximately 100-fold higher than the concentration observed in the cerebrospinal fluid of patients treated with 0.5 mg/kg of FTY720 (the clinically relevant dose mentioned is 0.5 mg/kg, though the text states 0.3 mg/kg in one instance). [1] |
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| Additional Infomation |
Fingolimod phosphate is a primary amino compound formed by the conversion of a hydroxyl group of fingolimod to its dihydrophosphate derivative. It is the active metabolite of fingolimod. It has antitumor, immunosuppressive, and sphingosine-1-phosphate receptor agonist effects. It is a monoalkyl phosphate, a primary amino compound, and a primary alcohol. Its function is related to that of fingolimod. Fingolimod phosphate (FTY720) is a sphingosine-1-phosphate (S1P) receptor agonist currently being used as a novel oral medication for the treatment of multiple sclerosis. FTY720 can prevent lymphocytes from leaving lymphoid organs and inhibit the infiltration of autoreactive lymphocytes into the central nervous system. Whether FTY720 directly affects microglia (innate immune cells of the central nervous system) is unclear. This study shows that FTY720 downregulates the production of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 by binding to the S1P1 receptor. FTY720 also upregulated the production of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GNF) by microglia. These results suggest that FTY720 can directly promote the neuroprotective effect of microglia. Therefore, FTY720 may not only be an effective drug for the treatment of multiple sclerosis, but also an effective drug for the treatment of other neurological diseases related to microglia activation. [1]
- Therapeutic Implications: Because FTY720 can cross the blood-brain barrier and directly promote the neuroprotective effects of microglia, it may be a promising therapeutic agent not only for MS but also for other neurologic diseases associated with microglial activation, such as spinal cord injury, stroke, amyotrophic lateral sclerosis, Alzheimer's disease, and epilepsy. [1] |
| Molecular Formula |
C19H34NO5P
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| Molecular Weight |
387.45100
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| Exact Mass |
387.217
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| CAS # |
402615-91-2
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| Related CAS # |
FTY720 (S)-Phosphate;402616-26-6;Fingolimod phosphate-d4;1794828-93-5
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| PubChem CID |
9908268
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
584.2±60.0 °C at 760 mmHg
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| Melting Point |
122-124ºC
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| Flash Point |
307.1±32.9 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.541
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| LogP |
4.27
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
26
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| Complexity |
409
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCCCC1=CC=C(C=C1)CCC(CO)(COP(=O)(O)O)N
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| InChi Key |
LRFKWQGGENFBFO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H34NO5P/c1-2-3-4-5-6-7-8-17-9-11-18(12-10-17)13-14-19(20,15-21)16-25-26(22,23)24/h9-12,21H,2-8,13-16,20H2,1H3,(H2,22,23,24)
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| Chemical Name |
[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate
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| Synonyms |
Fingolimod phosphate; FTY720 phosphate; 402615-91-2; FTY720 (R)-Phosphate; rac FTY720 Phosphate; 402616-23-3; FTY720-phosphate; fingolimod-P;
Fingolimod phosphate salt; 2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl dihydrogen phosphate; [2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate; fingolimod-phosphate; 402615-91-2;
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
Chloroform: 0.5 mg/ml
DMSO: ~100 mg/mL (~258 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5810 mL | 12.9049 mL | 25.8098 mL | |
| 5 mM | 0.5162 mL | 2.5810 mL | 5.1620 mL | |
| 10 mM | 0.2581 mL | 1.2905 mL | 2.5810 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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