| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
S1PR1[1]
Targets S1P receptor 1 (S1PR1) as an agonist. Upon binding, it induces S1PR1 internalization and degradation, leading to functional antagonism by reducing lymphocyte egress from lymph nodes. It is the active phosphorylated metabolite of the prodrug FTY720 (fingolimod), which is approved for relapsing multiple sclerosis. |
|---|---|
| ln Vitro |
FTY720 (S)-Phosphate functions as an S1PR1 agonist. FTY720 (S)-Phosphate (Tys, 1 μM) does not affect the induction of S1PR1 ubiquitination, but it does sustain the expression of the S1PR1 protein and improve the human pulmonary artery endothelial cells barrier through S1PR1. Additionally, FTY720 (S)-Phosphate (0.01–50 μM) lessens the recruitment of β-arrestin to S1PR1[1].
At 1 microM, (S)-FTY720-phosphonate maintains S1PR1 protein expression and enhances barrier function in human pulmonary artery endothelial cells via S1PR1 activation, without affecting S1PR1 ubiquitination. It activates Gi-coupled signaling pathways, which leads to decreased cAMP, activation of MAPK/ERK, and increased endothelial barrier integrity. |
| ln Vivo |
In mice suffering from bleomycin-induced acute lung injury (ALI), FTY720 (S)-Phosphate (0.5 mg/kg, ip) reduces lung tissue leukocyte infiltration and maintains S1PR1 expression in the lungs[1].
In a bleomycin-induced acute lung injury (ALI) mouse model, intraperitoneal administration of (S)-FTY720-phosphonate (0.5 mg/kg) preserves S1PR1 expression in mouse lungs, is protective against ALI, and attenuates lung tissue leukocyte infiltration. It reduces pulmonary edema, inflammatory cytokine levels, and improves survival outcomes. |
| Enzyme Assay |
Cell-free GTPgammaS binding assays are used to quantify S1PR1 activation. Membranes from S1PR1-expressing CHO cells are incubated with various agonist concentrations (0.1 nM-10 microM) in buffer containing [3⁵S]GTPgammaS (0.1 nM), 10 microM GDP, and 1 microM S1P. The mixture is incubated at 30degC for 60 min, then filtered and counted. EC50 values for agonist potency are calculated.
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| Cell Assay |
Human pulmonary artery endothelial cells (HPAECs) are grown to confluence in endothelial growth medium. Cells are treated with (S)-FTY720-phosphonate (0.01-10 microM) for 24-48 h. Barrier function is measured using electric cell-substrate impedance sensing (ECIS) or transendothelial electrical resistance (TEER). S1PR1 protein levels and ubiquitination are assessed by immunoblotting and immunoprecipitation.
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| Animal Protocol |
In mouse bleomycin-induced ALI models, C57BL/6 mice receive intratracheal bleomycin (2-3 U/kg) on day 0. (S)-FTY720-phosphonate (0.5 mg/kg) is administered intraperitoneally daily for 5-7 days. Endpoints include bronchoalveolar lavage fluid (BALF) leukocyte counts, protein concentration, cytokine levels (IL-6, TNF-alpha, MCP-1) by ELISA, lung wet/dry ratio, histopathology (H&E staining), and survival rate.
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| ADME/Pharmacokinetics |
The parent compound FTY720 (fingolimod) has well-characterized PK: long terminal half-life (~200 h in humans), high volume of distribution (>3000 L), low clearance (10.8 L/h), and extensive tissue distribution. (S)-FTY720-phosphonate, as the active metabolite, is likely to have similar PK characteristics, including slow elimination and sustained receptor modulation.
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| Toxicity/Toxicokinetics |
Toxicity data for (S)-FTY720-phosphonate is not publicly available. The parent compound fingolimod has known toxicities including bradycardia (first-dose), macular edema, elevated liver enzymes, and increased infection risk. The (S)-phosphate active metabolite would be expected to have similar safety concerns when used systemically in research.
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| References |
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| Additional Infomation |
(S)-FTY720-phosphonate is a research chemical, not approved for clinical use, though its parent compound fingolimod is FDA-approved for multiple sclerosis. It is a valuable tool for studying S1PR1-mediated endothelial barrier function, acute inflammation, and lymphocyte trafficking. It has improved potency compared to FTY720 and is the active form that directly interacts with S1PR1.
|
| Molecular Formula |
C20H36NO4P
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|---|---|
| Molecular Weight |
385.477907180786
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| Exact Mass |
385.238
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| CAS # |
1142015-10-8
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| Related CAS # |
FTY720 (S)-Phosphate;402616-26-6
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| PubChem CID |
42612062
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| Appearance |
White to off-white solid powder
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| LogP |
1.1
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
26
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| Complexity |
407
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(P(O)(O)=O)C[C@](N)(CO)CCC1=CC=C(CCCCCCCC)C=C1
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| InChi Key |
XDSPSYJWGHPIAZ-FQEVSTJZSA-N
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| InChi Code |
InChI=1S/C20H36NO4P/c1-2-3-4-5-6-7-8-18-9-11-19(12-10-18)13-14-20(21,17-22)15-16-26(23,24)25/h9-12,22H,2-8,13-17,21H2,1H3,(H2,23,24,25)/t20-/m0/s1
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| Chemical Name |
[(3S)-3-amino-3-(hydroxymethyl)-5-(4-octylphenyl)pentyl]phosphonic acid
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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) |
DMSO: 25 mg/mL (64.85 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5942 mL | 12.9708 mL | 25.9417 mL | |
| 5 mM | 0.5188 mL | 2.5942 mL | 5.1883 mL | |
| 10 mM | 0.2594 mL | 1.2971 mL | 2.5942 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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