Fingolimod (FTY720) HCl (Synonyms: Gilenia; FTY 720; FTY-720) |
| رقم الكتالوجGC14807 |
فينغوليمود (FTY720) HCl (FTY720)، وهو مشتق من السفينجوزين، هو عامل تعديل لمستقبلات سفينجوزين 1- فسفات (S1P) قوية.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 162359-56-0
Sample solution is provided at 25 µL, 10mM.
Fingolimod (FTY720), an immunosuppressant agent, usually used in the treatment of multiple sclerosis, also has anticancer actions and can act as an HDACi (Histone deacetylase inhibitors)[1].
In vitro, Fingolimod at 7.5 or 10 µM, induced a significant reduction in cell viability in D283 and DAOY cultures, also led to a significant increase in the levels of acetylated H3[1]. In vitro, Fingolimod showed cytotoxic antiproliferative effects against androgen-dependent and -independent prostate cancer cells with IC50 ranging from 3.0 ± 0.3 to 6.8 ± 1.7 µM[2]. Jurkat T-lymphocytes exposure to Fingolimod suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 1.51 µM[3]. Fingolimod reduced the proliferation and viability of Ph(+) and Ph(-) ALL cell lines and patient samples with IC 50 values for viability between 5.3 to 7.9 µM[4]. Fingolimod differentially suppressed the viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC50 values of 6.1, 6.3, and 4.5 µM, respectively[5].
In vivo, E13 C57BL/6 wildtype mice were treated with 1 mg/kg significantly increased the survival of DCX+ neurons in the DG (dentate gyrus) and the SVZ (the subventricular zone) 4 weeks after irradiation as well as a slight increase of proliferating cells[6]. In vivo, 5xFAD mice were treated with 1 mg/kg/day fingolimod decreased both peripheral blood lymphocyte counts and brain Aβ levels, but treated with 0.03 mg/kg/day improved memory, decreased activation of brain microglia and astrocytes, and restored hippocampal levels of GABA and glycerophosphocholine with no effect on circulating lymphocyte counts[7]. In vivo, C57BL/6JOlaHsd mice were treated with 0.5 mg/kg fingolimod increased lesion size (stroke) but decreased ipsilateral brain atrophy in younger mice, without an effect on behavioural outcomes[8].
References:
[1] Perla AS, et al. Fingolimod (Fingolimod) reduces viability and survival and increases histone H3 acetylation in medulloblastoma cells. Pediatr Hematol Oncol. 2020 Mar;37(2):170-175.
[2] Allam RM, et al. Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells. Toxicol Lett. 2018 Jul;291:77-85.
[3] Chang WT, et al. Actions of Fingolimod (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.
[4] Wallington-Beddoe CT, et al. Fingolimod produces caspase-independent cell death of acute lymphoblastic leukemia cells. Autophagy. 2011 Jul;7(7):707-15.
[5] Bai LY, et al. Fingolimod Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism. Sci Rep. 2017 Jul 17;7(1):5600.
[6] Metzdorf J, et al. Fingolimod for Irradiation-Induced Neurodegeneration. Front Neurosci. 2019 Jul 9;13:699.
[7] Carreras I, et al. Dual dose-dependent effects of fingolimod in a mouse model of Alzheimer's disease. Sci Rep. 2019 Jul 29;9(1):10972.
[8] Diaz Diaz AC, et al. Preclinical Evaluation of Fingolimod in Rodent Models of Stroke With Age or Atherosclerosis as Comorbidities. Front Pharmacol. 2022 Jul 13;13:920449.
| Cell experiment [1]: | |
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Cell lines |
bone marrow derived macrophages |
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Preparation Method |
BMDMs were stimulated with MSU, GM-CSF/IL-1β or nigericin ± fingolimod (2.5 µM) or febuxostat (200 µM) and UA levels, ROS, XO, and PP2A activities, Xdh (XO) expression and secreted IL-1β levels were determined. |
|
Reaction Conditions |
2.5 µM; 3 h |
|
Applications |
Fingolimod reduced intracellular and secreted UA (catalyzes uric acid) levels, Xdh expression, XO (Xanthine oxidase) activity, ROS (reactive oxygen species) generation and IL-1β secretion, whereas febuxostat enhanced PP2A (Protein phosphatase 2A) activity. |
| Animal experiment [2]: | |
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Animal models |
C57BL6/J mice |
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Preparation Method |
Mechanical force-induced HSs were generated in C57BL6/J mice by suturing a dorsal incision and applying a stretching device on Days 6, 8, 10, and 12. On Days 8, 10, and 12, intracutaneous Fingolimod (10 µM) or control vehicle injections were performed. On Day 14, scar tissues and blood were procured and subjected to histology and flow cytometry. |
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Dosage form |
10 µM; i.c. |
|
Applications |
Flow cytometry showed that Fingolimod decreased the frequencies of macrophages with M2 predominance in the scars but had no effect on total, CD4+, or CD8a+ T cell frequencies. Fingolimod also decreased the vascular endothelial cell frequencies in the scar along with the microvessels, as determined by immunohistochemistry. Compared to the vehicles, Fingolimod treatment significantly reduced the gross scar area and the cross-sectional scar area on histology. On the other hand, Fingolimod tended to reduce white blood cells and significantly reduced the lymphocyte frequencies in the blood. |
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References: [1] Elsayed S, et al. Protein phosphatase 2A regulates xanthine oxidase-derived ROS production in macrophages and influx of inflammatory monocytes in a murine gout model. Front Pharmacol. 2022 Nov 17;13:1033520. |
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| Cas No. | 162359-56-0 | SDF | |
| المرادفات | Gilenia; FTY 720; FTY-720 | ||
| Chemical Name | 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol;hydrochloride | ||
| Canonical SMILES | CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N.Cl | ||
| Formula | C19H34ClNO2 | M.Wt | 343.94 |
| الذوبان | DMSO : ≥ 100 mg/mL; Water : 50 mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9075 mL | 14.5374 mL | 29.0748 mL |
| 5 mM | 0.5815 mL | 2.9075 mL | 5.815 mL |
| 10 mM | 0.2907 mL | 1.4537 mL | 2.9075 mL |
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- Purity: >99.50%
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Related Biological Data
BCL-2/BCL-XL phosphorylation augment PUMA-induced apoptosis. PP2A activator FTY720 partially abolished PUMAinduced phosphorylation of BCL-2 and BCL-XL as well as caspase-3 cleavage in SKOV3 cells. SKOV3 cells were infected with Ad-PUMA or Ad-GFP adenovirus for 48 h in the presence of 2.5 μM FTY720.
SKOV3 cells were infected with Ad-PUMA or Ad-GFP adenovirus for 48 h in the presence of 2.5 μM FTY720(GLPBIO).
BBA-Mol Basis Dis 1868.12 (2022): 166553 PMID: 36122664 IF: 6.2001 -
Related Biological Data
SPHK1 inhibition reverses the antiapoptotic effect in bladder cancer cells. (A) Inhibition efficiency of SPHK1 inhibitor FTY‑720 as determined via western blotting.
FTY‑720 was purchased from GLPBio.
Int J Mol Med 48.5 (2021): 1-13 PMID: 34549307 IF: 4.102
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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