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.

Physicochemical Properties

Molecular Formula	C19H34NO5P
Molecular Weight	387.45100
Exact Mass	387.217
CAS #	402615-91-2
Related CAS #	FTY720 (S)-Phosphate;402616-26-6;Fingolimod phosphate-d4;1794828-93-5
PubChem CID	9908268
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	584.2±60.0 °C at 760 mmHg
Melting Point	122-124ºC
Flash Point	307.1±32.9 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.541
LogP	4.27
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	14
Heavy Atom Count	26
Complexity	409
Defined Atom Stereocenter Count	0
InChi Key	LRFKWQGGENFBFO-UHFFFAOYSA-N
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)
Chemical Name	[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate
Synonyms	Fingolimod phosphate; FTY720 phosphate; 402615-91-2; FTY720 (R)-Phosphate; rac FTY720 Phosphate; 402616-23-3; FTY720-phosphate; fingolimod-P;
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)

Biological Activity

Targets	sphingosine 1-phosphate (S1P)(IC50 = 0.033 nM, in K562 and NK cells); PAK1
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].
ln Vivo	FTY720 is effective in Ph+ but not Ph- ALL xenografts using an early disease model. FTY720 produces a significant reduction in disease burden in the Ph+ ALL xenografts using an early disease model. Ph+ human ALL xenografts responds to FTY720 with an 80 % reduction in overall disease if treatment has been initiated early on. In contrast, treatment of mice with FTY720 does not result in reduced leukemia compared to controls using four separate human Ph- ALL xenografts.
Animal Protocol	Dissolved in 2% ethanol or saline; 5 and 10 mg/kg; i.p. injection NOD/SCIDγc / mice bearing ALL cells.
References	[1]. Fingolimod phosphate promotes the neuroprotective effects of microglia. J Neuroimmunol. 2013 Mar 15;256(1-2):13-8.
Additional Infomation	Fingolimod phosphate is a primary amino compound that is fingolimod in which one on the hydroxy groups has been converted into its dihydrogen phosphate derivative. It is the active metabolite of fingolimod. It has a role as an antineoplastic agent, an immunosuppressive agent and a sphingosine-1-phosphate receptor agonist. It is a monoalkyl phosphate, a primary amino compound and a primary alcohol. It is functionally related to a fingolimod. Fingolimod phosphate (FTY720) is a sphingosine 1-phosphate (S1P) receptor agonist that is being used as a new oral drug for multiple sclerosis. FTY720 prevents lymphocytes from moving out of the lymphoid organs and inhibits autoreactive lymphocytes from infiltrating the central nervous system. Whether FTY720 directly affects microglia-the innate immune cells of the central nervous system-is unclear. Here we show that FTY720 binds S1P1 receptors to downregulate activated microglial production of such pro-inflammatory cytokines as tumor necrosis factor-α, interleukin-1β, and interleukin-6. FTY720 also upregulates microglial production of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor. These results suggested that FTY720 directly promotes the neuroprotective effects of microglia. Therefore, FTY720 may be a potent therapeutic agent for not only multiple sclerosis but also other neurologic diseases associated with microglial activation.[1]

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.