Fingolimod (FTY720) HCl

Catalog No.S5002 Batch:S500209

Technical Data

Formula	C₁₉H₃₃NO₂.HCl
Molecular Weight	343.9	CAS No.	162359-56-0
Solubility (25°C)*	In vitro	DMSO	69 mg/mL (200.63 mM)
		Water	69 mg/mL (200.63 mM)
		Ethanol	69 mg/mL (200.63 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Fingolimod (FTY720, Fingolimod Hydrochloride) HCl is a S1P antagonist with IC50 of 0.033 nM in K562, and NK cells. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.

Targets

S1P receptor ^[1]
(K562, NK cells )

0.033 nM

In vitro

The inhibitory effect of S1P is revered by various concentrations of FTY720, with IC50 effect of 173 nM. In addition, FTY720 (10 nM) alone exerts no effect on the expression of co-stimulatory molecules. FTY720 reverses the increased expression of HLA-I induced by S1P for both the percentages of cells and the MFI, upon comparing the effect of S1P to the effect of combining S1P with FTY720. ^[1] Medium and high-dose FTY720-P also enhances the levels of TGF-β1. TGF-β1 and Foxp3 mRNA expression are upregulated in the high-dose FTY720-P group. The proliferation of effector T cells is suppressed significantly in the medium and high-dose FTY720-P group at a Treg/Teff cell ratio of 1:1. At a ratio of 1:1, the proliferation of effector T cells is also suppressed in the high-dose FTY720 group. ^[2]

In 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. ^[3]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Immature DCs Concentrations 10 nM Incubation Time 4 hours Method Immature DCs are left intact or are incubated with 2 μM S1P, 10 nM FTY720, 10 nM SEW2871 or the combinations of S1P with these drugs for 4 hours. As a control 1 μg/mL LPS is used. The cells are washed and incubated in a 96-well plate (v-bottom, 2 × 10⁵ cells per well), washed again and resuspended in PBS buffer containing 0.1% sodium azide. They are labeled with 1 μg/mL FITC-conjugated mouse anti-human CD80, 1 μg/mL FITC-conjugated mouse anti-human CD83, 1 μg/mL FITC-conjugated mouse anti-human CD86, 1 μg/mL FITC-conjugated mouse anti-human HLA-class I, 1 μg/mL FITC-conjugated mouse anti-human HLA-DR, 1 μg/mL FITC-conjugated mouse anti-human HLA-E, or 1 μg/mL FITC-conjugated mouse IgG as a control. The cells are washed twice, and examined in the flow cytometer. Markers are set according to the isotype control FITC-conjugated mouse IgG. To stain NK cells with antibodies for various NK cell activating receptors, they are either left untreated or incubated with 2 μM S1P for 4 hours, 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 min at 4 °C. NK cells are also stained with 1 μg/mL FITC-conjugated anti-killer inhibitory receptor (KIR)/CD158 antibody which recognizes KIR2DL2, KIR2DL3, KIR2DS2 and KIR2DS4, and as a control with FITC-conjugated mouse IgG. The cells are washed twice, and examined in the flow cytometer. Markers are set according to the isotype control PE-conjugated or FITC-conjugated mouse IgG.
Animal Study:^{^[3]}	Animal Models NOD/SCIDγc^−/− mice bearing ALL cells. Dosages 5 mg/kg/day, 10 mg/kg/day Administration Administered via i.p.

Cell Assay:^{^[1]}

Cell lines
Immature DCs
Concentrations
10 nM
Incubation Time
4 hours
Method
Immature DCs are left intact or are incubated with 2 μM S1P, 10 nM FTY720, 10 nM SEW2871 or the combinations of S1P with these drugs for 4 hours. As a control 1 μg/mL LPS is used. The cells are washed and incubated in a 96-well plate (v-bottom, 2 × 10⁵ cells per well), washed again and resuspended in PBS buffer containing 0.1% sodium azide. They are labeled with 1 μg/mL FITC-conjugated mouse anti-human CD80, 1 μg/mL FITC-conjugated mouse anti-human CD83, 1 μg/mL FITC-conjugated mouse anti-human CD86, 1 μg/mL FITC-conjugated mouse anti-human HLA-class I, 1 μg/mL FITC-conjugated mouse anti-human HLA-DR, 1 μg/mL FITC-conjugated mouse anti-human HLA-E, or 1 μg/mL FITC-conjugated mouse IgG as a control. The cells are washed twice, and examined in the flow cytometer. Markers are set according to the isotype control FITC-conjugated mouse IgG. To stain NK cells with antibodies for various NK cell activating receptors, they are either left untreated or incubated with 2 μM S1P for 4 hours, 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 min at 4 °C. NK cells are also stained with 1 μg/mL FITC-conjugated anti-killer inhibitory receptor (KIR)/CD158 antibody which recognizes KIR2DL2, KIR2DL3, KIR2DS2 and KIR2DS4, and as a control with FITC-conjugated mouse IgG. The cells are washed twice, and examined in the flow cytometer. Markers are set according to the isotype control PE-conjugated or FITC-conjugated mouse IgG.

Animal Study:^{^[3]}

Animal Models
NOD/SCIDγc^−/− mice bearing ALL cells.
Dosages
5 mg/kg/day, 10 mg/kg/day
Administration
Administered via i.p.

References

[4] Nikolova Z, et al. Transpl Immunol. 2001, 8(4), 267-277.

+ Expand

Customer Product Validation

: Data from [Blood, 2012, 119, 2176-2177]

: Data from [Blood, 2012, 119, 2176-2177]

: Data from [Mol Med, 2011, 17, 717- 725 ]

Selleck's Fingolimod (FTY720) HCl has been cited by 128 publications

Anti-PD-1 therapy triggers Tfh cell-dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes [ J Exp Med, 2024, 221(4)e20232104]	PubMed: 38417020
Germinal centers output clonally diverse plasma cell populations expressing high- and low-affinity antibodies [ Cell, 2023, 10.1016/j.cell.2023.10.022]	PubMed: 37951212
Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8+ exhausted-like T cells [ Nat Commun, 2023, 14(1):7709.]	PubMed: 38001101
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory [ Proc Natl Acad Sci U S A, 2023, 120(30):e2304319120]	PubMed: 37459511
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory [ Proc Natl Acad Sci U S A, 2023, 120(30):e2304319120]	PubMed: 37459511
TSLP in DRG neurons causes the development of neuropathic pain through T cells [ J Neuroinflammation, 2023, 20(1):200]	PubMed: 37660072
T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections [ Cell Rep, 2023, 10.1016/j.celrep.2023.113448]	PubMed: 37967010
TSLP in DRG neurons causes the development of neuropathic pain through T cells [ J Neuroinflammation, 2023, 20(1):200]	PubMed: 37660072
SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML [ Oncogene, 2023, 42(50):3670-3683]	PubMed: 37891368
Bruton's tyrosine kinase inhibition reduces disease severity in a model of secondary progressive autoimmune demyelination [ Acta Neuropathol Commun, 2023, 11(1):115]	PubMed: 37438842

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