FTY720 (Fingolimod) Hydrochloride

Katalognr.S5002 Batch:S500208

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Tekniska data

Formel

C19H33NO2.HCl
Molekylvikt 343.9 CAS-nr. 162359-56-0
Löslighet (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)
In Vivo (Tillsätt lösningsmedel till produkten individuellt och i ordning.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml betyder svårlösligt eller olösligt.
* Vänligen notera att Selleck testar lösligheten för alla förbindelser internt, och den faktiska lösligheten kan skilja sig något från publicerade värden. Detta är normalt och beror på små variationer mellan olika partier.
* Rumstempererad frakt (Stabilitetstester visar att denna produkt kan fraktas utan några kylåtgärder.)

Beredning av stamlösningar

Biologisk aktivitet

Beskrivning Fingolimod (FTY720, Fingolimod Hydrochloride) HCl är en S1P-antagonist med ett IC50-värde på 0,033 nM i K562- och NK-celler. Använd koksaltlösning istället för PBS för spädningar. PBS kan orsaka utfällning.Lösningar är instabila och bör beredas färska.
Mål
S1P receptor
(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. 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.

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.

Protokoll (från referens)

Cellanalys:

[1]
  • Cellinjer

    Immature DCs

  • Koncentrationer

    10 nM

  • Inkubationstid

    4 hours

  • Metod

    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.
Djurstudie:

[3]
  • Djurmodeller

    NOD/SCIDγc−/− mice bearing ALL cells.

  • Doseringar

    5 mg/kg/day, 10 mg/kg/day

  • Administrering

    Administered via i.p.

Referenser

  • https://pubmed.ncbi.nlm.nih.gov/19823820/
  • https://pubmed.ncbi.nlm.nih.gov/22576630/
  • https://pubmed.ncbi.nlm.nih.gov/22570713/
  • https://pubmed.ncbi.nlm.nih.gov/11316070/

Kundvalidering av produkt

<p> </p><p> </p><p>Fingolimod blocks antitumor immunity and prevents rejection of myeloma and B-cell lymphoma in TCR-transgenic SCID mice. (A) Id-specific TCR-transgenic (TCR-tg) SCID mice were inoculated subcutaneously with 1.6  105 MOPC315 myeloma cells and treated daily with either fingolimod (FTY720, Selleck Chemicals; 2ug/g bodyweight) or with vehicle only (0.8% DMSO; Sigma-Aldrich) delivered intraperitoneally. Tumor growth was followed by palpation. Mice were euthanized when the tumor reached 10 mm in diameter (n=14-17). (B) Id-specific TCR-transgenic SCID mice were inoculated subcutaneously with 1.6  105 F9 B-lymphoma cells and treated daily with fingolimod or with vehicle only. F9 cells are A20 B-lymphoma cells transfected with Id-containing L-chain from MOPC3157 (n=14-16). (C) Nontransgenic SCID mice were inoculated subcutaneously with 1.6  105 MOPC315 cells and treated daily with fingolimod or with vehicle only (n=8).</p>

Data från [ Blood , 2012 , 119, 2176-2177 ]

<p> </p><p>Fingolimod blocks antitumor immunity and prevents rejection of myeloma and B-cell lymphoma in TCR-transgenic SCID mice. Id-specific TCR-transgenic and nontransgenic SCID mice were inoculated subcutaneously with 105 MOPC315 myeloma cells embedded in Matrigel.9 TCR-transgenic SCID mice were treated daily with fingolimod (1ug/g bodyweight) or with vehicle only (n=8-10). SCID mice were left untreated (n =2). At day 8, draining lymph nodes and Matrigel plugs were dissected and analyzed by flow cytometry.9 (D) CD69 expression on gated Id-specific CD4 T cells in draining lymph nodes of representative TCR-transgenic SCID mice treated with vehicle only (top) or fingolimod (bottom). Dotted lines indicate an isotype-matched control antibody. (E) Number of Id-specific T cells per Matrigel plug (mean  SEM). (F) Expression of the activation marker MHC class II on Matrigel-infiltrating CD11b macrophages (geometric mean  SEM). P values were calculated with the log-rank test (A-C) and the t test (E-F). ns indicates not significant.</p>

Data från [ Blood , 2012 , 119, 2176-2177 ]

<p>FTY720 treatment of ECM decreases lymphocyte numbers and granzyme A mRNA in the brain. (A) Relative CD8+ and (B) CD4+ T-cell numbers isolated from the brains of mice infected for 6 d. Numbers were decreased in animals treated with FTY720 1 d before infection and 1 d p.i. (CD4+: P < 0.5 and P < 0.001, CD8+: P < 0.5 and P < 0.01 respectively, KW and DMC, two pooled IE, n ≥ 4/group/IE) (C) GZMA mRNA levels were decreased in the brains of FTY720-treated animals compared with control animals: for (FTY720 [–1], P < 0.05, FTY720 [+1] P > 0.05 and FTY720 [+3], P < 0.01; KW and DMC, two pooled IE, n ≥ 3/group/IE).</p>

Data från [ Mol Med , 2011 , 17, 717- 725 ]

Sellecks FTY720 (Fingolimod) Hydrochloride Har citerats av 141 Publikationer

Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Preclinical Pancreatic Cancer Models [ Oncol Res, 2026, 34(3):12] PubMed: 41799523
Targeting Sphingosine-1-Phosphate Signaling Attenuates Doxorubicin-Aggravated Bone Loss in Obese Breast Cancer Mice [ Smart Med, 2026, 5(2):e70031] PubMed: 42079390
Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer [ Cancer Cell, 2025, S1535-6108(25)00319-8] PubMed: 40816292
A pan-immunotherapy signature to predict intratumoral CD8+ T cell expansions [ Nat Commun, 2025, 16(1):9175] PubMed: 41115883
S1PR1-biased activation drives the resolution of endothelial dysfunction-associated inflammatory diseases by maintaining endothelial integrity [ Nat Commun, 2025, 16(1):1826] PubMed: 39979282
PLZF-expressing CD4+ T cells promote tissue-resident memory T cells in breaking immune tolerance in allergic asthma via IL-15/IL-15Rα signaling [ Cell Commun Signal, 2025, 23(1):138] PubMed: 40089783
PP2A attenuates α-amanitin-induced liver injury by promoting autophagy and inhibiting apoptosis in mouse models [ Chem Biol Interact, 2025, 417:111558] PubMed: 40379039
Helminth infection induces neuroimmune remodeling and clinical remission in a mouse model of multiple sclerosis [ bioRxiv, 2025, 2025.09.02.672458] PubMed: 40950041
Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity [ Nat Commun, 2024, 15(1):10635] PubMed: 39639025
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

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