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FTY720 (Fingolimod) Hydrochloride S1P Receptor antagoniste

Name: FTY720 (Fingolimod) Hydrochloride
Brand: Selleck Chemicals
SKU: S5002
Rating: 5 (136 reviews)

Réf. CatalogueS5002

Fingolimod (FTY720, Fingolimod Hydrochloride) HCl est un antagoniste de S1P avec une IC50 de 0,033 nM dans les cellules K562 et NK. Veuillez utiliser une solution saline plutôt que du PBS pour les dilutions. Le PBS peut provoquer une précipitation.

FTY720 (Fingolimod) Hydrochloride S1P Receptor antagoniste Chemical Structure

Structure chimique

Poids moléculaire: 343.9

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Contrôle Qualité

Lot : Pureté : 99.99%

99.99

Cibles apparentées	CXCR Hedgehog/Smoothened PKA Adrenergic Receptor AChR 5-HT Receptor Histamine Receptor Dopamine Receptor Ras KRas
Autre S1P Receptor Inhibiteurs	JTE 013 PF 429242 CAY10444 CYM5541 CYM-5520 SEW 2871 SLF1081851 hydrochloride CYM50308 MP-A08 Etrasimod(APD334)

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
human U2OS cells	Function assay			Agonist activity at human S1P1 receptor expressed in human U2OS cells co-expressing eGFP assessed as receptor internalization into cytoplasm using Hoechst dye staining, EC50=0.002 μM.	22104144
human PC3 cells	Cytotoxic assay		72 h	Cytotoxicity against human PC3 cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=9.8 μM.	24273632
human NALM6 cells	Cytotoxic assay		72 h	Cytotoxicity against Ph-negative human NALM6 cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=9.6 μM.	24273632
human CCRF-CEM cells	Cytotoxic assay		72 h	Cytotoxicity against Ph-negative human CCRF-CEM cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=6.8 μM.	24273632
human SUP-B15 cells	Cytotoxic assay		72 h	Cytotoxicity against Ph-positive human SUP-B15 cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=6.8 μM.	24273632
human DU145 cells	Cytotoxic assay		72 h	Cytotoxicity against human DU145 cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=6.5 μM.	24273632
human BV173 cells	Cytotoxic assay		72 h	Cytotoxicity against Ph-positive human BV173 cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=6.3 μM.	24273632
human BLIN-1 cells	Cytotoxic assay		72 h	Cytotoxicity against Ph-negative human BLIN-1 cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=5.5 μM.	24273632
mouse bone marrow cells	Cytotoxic assay		72 h	Cytotoxicity against BCR-ABL fusion protein 190 expressing mouse bone marrow cells after 72 hrs by vital dye exclusion/flow cytometric analysis, IC50=3.3 μM.	24273632
Sf9 insect cells	Function assay		1 h	Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	24809814
mouse MN9D cells	Function assay	5 μM		Induction of PP2A catalytic subunit activity in mouse MN9D cells assessed as phosphate level at 5 uM	25050165
rat PC12 cells	Function assay	5 μM	30 to 120 mins	Induction of PP2A catalytic subunit activity in rat PC12 cells assessed as phosphate level at 5 uM measured 30 to 120 mins.	25050165
mouse MN9D cells	Function assay	0.16 μM	24 h	Neuroprotective activity in mouse MN9D cells assessed as stimulation of BDNF expression at 0.16 uM after 24 hrs	25050165
mouse MN9D cells	Function assay	0.16 μM	72 h	Neuroprotective activity in mouse MN9D cells assessed as blocking of TNF-alpha associated toxicity at 0.16 uM after 72 hrs by Trypan blue staining.	25050165
CHO	Function assay			Displacement of [33P]sphingosine 1 phosphate from human S1P1 receptor expressed in CHO cells, IC50=0.84μM.	15615513
CHO	Function assay			Displacement of [33P]sphingosine 1 phosphate from human S1P5 receptor expressed in CHO cells, IC50=2.1μM.	15615513
Jurkat	Function assay		18 hrs	Reversal of inhibition of mitochondrial function in human Jurkat cells after 18 hrs in presence of Z-VAD-fmk	17400555
T-cells	Function assay		96 hrs	Immunosuppressive activity in BALB/c/C57BL/6 mouse T cells assessed as inhibition of alloantigen-induced cell proliferation after 96 hrs by measuring [3H]thymidine uptake by mixed lymphocyte reaction assay, IC50=0.0061μM.	21456524
SK-BR-3	Antiproliferative assay		78 hrs	Antiproliferative activity against human SK-BR-3 cells assessed as growth inhibition after 78 hrs by WST-1 assay, IC50=5μM.	21456524
MDA-MB-231	Antiproliferative assay		78 hrs	Antiproliferative activity against human MDA-MB-231 cells assessed as growth inhibition after 78 hrs by WST-1 assay, IC50=5μM.	21456524
HCT116	Antiproliferative assay		78 hrs	Antiproliferative activity against human HCT116 cells assessed as growth inhibition after 78 hrs by WST-1 assay, IC50=5μM.	21456524
SW620	Antiproliferative assay		78 hrs	Antiproliferative activity against human SW620 cells assessed as growth inhibition after 78 hrs by WST-1 assay, IC50=5μM.	21456524
MCF7	Antiproliferative assay		78 hrs	Antiproliferative activity against human MCF7 cells assessed as growth inhibition after 78 hrs by WST-1 assay, IC50=5μM.	21456524
LNCAP-AI	Antiproliferative assay		78 hrs	Antiproliferative activity human LNCAP-AI cells assessed as growth inhibition after 78 hrs by WST-1 assay, IC50=5μM.	21456524
MGC803	Antitumor assay	10 mg/kg	20 days	Antitumor activity against human MGC803 cells xenografted in nude mouse assessed as inhibition of tumor growth at 10 mg/kg for 20 days	21456524
U2OS	Function assay		18 hrs	Agonist activity at human S1P1 receptor expressed in EDG1-bla U2OS cells incubated for 18 hrs prior to GenBlazer substrate addition by beta-arrestin recruitment assay, EC50=0.0072μM.	26687487
FL5.12A	Cytotoxicity assay		48 hrs	Cytotoxicity against mouse FL5.12A cells after 48 hrs by DAPI staining-based flow cytometric analysis, IC50=2.4μM.	27475534
SH-SY5Y	Cytotoxicity assay		24 hrs	Cytotoxicity against human SH-SY5Y cells measured after 24 hrs by crystal-violet staining based assay, EC10=0.54μM.	27913115
SK-N-SH	Cytotoxicity assay		24 hrs	Cytotoxicity against human SK-N-SH cells measured after 24 hrs by crystal-violet staining based assay, EC10=0.55μM.	27913115
U118MG	Cytotoxicity assay		24 hrs	Cytotoxicity against human U118MG cells measured after 24 hrs by crystal-violet staining based assay, EC10=0.61μM.	27913115
SH-SY5Y	Function assay			Agonist activity at sphingosine-1-phosphate receptor in human SH-SY5Y cells assessed as increase in cAMP level at EC10 by direct immunoassay	27913115
U118MG	Function assay			Agonist activity at sphingosine-1-phosphate receptor in human U118MG cells assessed as increase in cAMP level at EC10 by direct immunoassay	27913115
SK-N-SH	Function assay			Agonist activity at sphingosine-1-phosphate receptor human SK-N-SH cells assessed as increase in cAMP level at EC10 by direct immunoassay	27913115
HEK293	Function assay		18 hrs	Agonist activity at sphingosine-1-phosphate receptor (unknown origin) expressed in HEK293 cells assessed as increase in cAMP level at EC10 after 18 hrs by CRE-responsive renilla luciferase reporter gene assay	27913115
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
FL5.12	Cytotoxicity assay		48 hrs	Cytotoxicity against mouse FL5.12 cells after 48 hrs by DAPI or propidium iodide staining-based flow cytometric analysis, IC50=2.1μM.	30292898
FL5.12	Cytotoxicity assay	10 uM	3 hrs	Cytotoxicity against mouse FL5.12 cells assessed as vacuole formation at 10 uM after 3 hrs by fluorescence microscopic analysis	30292898
FL5.12	Cytotoxicity assay	2.5 uM	3 hrs	Cytotoxicity against mouse FL5.12 cells assessed as vacuole formation at 2.5 uM after 3 hrs by fluorescence microscopic analysis	30292898
HepG2	qHTS assay			HepG2 cells viability qHTS for Zika virus inhibitors	33229545
CHO	Function assay			Agonist activity at human S1P3 receptor expressed in CHO cells assessed as increase in calcium flux by aequorin-derived luminescence assay, EC50=2.51189μM.	ChEMBL
CHO	Function assay			Agonist activity at human S1P5 receptor expressed in CHO cells assessed as increase in calcium flux by aequorin-derived luminescence assay, EC50=3.16228μM.	ChEMBL
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Informations chimiques, stockage et stabilité

Poids moléculaire	343.9	Formule	C₁₉H₃₃NO₂.HCl	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	162359-56-0	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	Fingolimod Hydrochloride,FTY720			Smiles	CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N.Cl

Solubilité

In vitro
Lot:

DMSO : 69 mg/mL (200.63 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : 69 mg/mL

Ethanol : 69 mg/mL

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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.
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	3.450mg/ml (10.03mM)	Taking the 1 mL working solution as an example, add 50 μL 69 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
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.
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.
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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	S1P receptor (K562, NK cells ) 0.033 nM
In vitro	L'effet inhibiteur du S1P est inversé par diverses concentrations de FTY720, avec un effet IC50 de 173 nM. De plus, le FTY720 (10 nM) seul n'exerce aucun effet sur l'expression des molécules co-stimulatrices. Le FTY720 inverse l'augmentation de l'expression de HLA-I induite par le S1P, tant pour les pourcentages de cellules que pour le MFI, en comparant l'effet du S1P à l'effet de la combinaison du S1P avec le FTY720. Le FTY720-P à doses moyennes et élevées augmente également les niveaux de TGF-β1. L'expression de l'ARNm de TGF-β1 et de Foxp3 est régulée à la hausse dans le groupe FTY720-P à dose élevée. La prolifération des lymphocytes T effecteurs est significativement supprimée dans le groupe FTY720-P à doses moyennes et élevées à un rapport cellules Treg/Teff de 1:1. À un rapport de 1:1, la prolifération des lymphocytes T effecteurs est également supprimée dans le groupe FTY720 à dose élevée.
In vivo	Le FTY720 est efficace dans les xénogreffes de LLA Ph⁺ mais pas Ph^- utilisant un modèle de maladie précoce. Le FTY720 produit une réduction significative du fardeau de la maladie dans les xénogreffes de LLA Ph⁺ utilisant un modèle de maladie précoce. Les xénogreffes humaines de LLA Ph⁺ répondent au FTY720 avec une réduction de 80 % de la maladie globale si le traitement a été initié tôt. En revanche, le traitement des souris avec le FTY720 n'entraîne pas de réduction de la leucémie par rapport aux contrôles utilisant quatre xénogreffes humaines distinctes de LLA Ph^-.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/19823820/ [2] https://pubmed.ncbi.nlm.nih.gov/22576630/ [3] https://pubmed.ncbi.nlm.nih.gov/22570713/ [4] https://pubmed.ncbi.nlm.nih.gov/11316070/

Applications

Méthodes	Biomarqueurs	PMID
Western blot	p-AKT / AKT / p-mTOR / mTOR / p-GSK3β / GSK3β / p-IKKα/β / IKKα / NF-κB / Survivin p-STAT3 / STAT3 / Bcl-xl / Bcl-2 / Bax Cyclin D1 / CDK4 / cyclin E / CDK2 / p27 / p16	28717222
Immunofluorescence	NF-κB N-cadherin / Vimentin	28717222
Growth inhibition assay	Cell viability	28717222

Informations sur lessai clinique

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
NCT05141669	Completed	Multiple Sclerosis	Novartis Pharmaceuticals\|Novartis	May 18 2020	--
NCT03345940	Terminated	Relapsing Remitting Multiple Sclerosis	Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta\|Patient-Centered Outcomes Research Institute\|Universita degli Studi di Genova	April 30 2017	Phase 4
NCT02575365	Terminated	Cognition\|Brain Volume Loss	Novartis Pharmaceuticals\|Novartis	February 16 2016	Phase 4

Support technique

Instructions de manipulation

Tel: +1-832-582-8158 Ext:3

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