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Fingolimod (FTY720).

S1P受体激动剂,Fingolimod hydrochloride是鞘氨醇1-磷酸 (S1P)拮抗剂，在K562和NK细胞中的IC50 为0.033 nM。

目录号: PC10668 纯度: ≥98%

CAS No. :162359-56-0

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中文名称	Fingolimod (FTY720).
中文别名	盐酸芬戈莫德;2-氨基-2-[2-(4-辛烷基苯基)乙基]-1,3-丙二醇盐酸盐;芬戈莫德;芬戈莫德盐酸盐;Fingolimod (FTY720) HCl 抑制剂;Fingolimod FTY120 芬戈莫徳;Fingolimod Hydrochloride 芬戈莫德盐酸盐;盐酸芬戈莫德 Fingolimod Hydrochloride;盐酸芬戈莫德(FTY-720);盐酸芬戈莫德标准品;2-氨基-2-[2-(4-正辛基苯基)乙基]丙烷-1,3-二醇盐酸盐;芬戈莫德(FTY-720);盐酸2-氨基-2-{2-(4-辛烷基)乙基}丙二醇;盐酸曲吡那敏;鞘氨醇;芬戈莫德盐酸;苏戈莫德杂质;盐酸芬戈莫德(标准品);盐酸芬革莫德, S1P拮抗剂
英文名称	Fingolimod (FTY720)
英文别名	2-Amino-2-(4-octylphenethyl)propane-1,3-diol hydrochloride;2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride;fingolimod hydrochloride;FTY720;Fingolimod HCl;FTY720 HYDROCHLORIDE;2-Amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol,HCl;Fingolimod HCL(FTY720);2-AMINO-2-[2-(4-OCTYLPHENYL)-ETHYL]-1,3-PROPANEDIOL;Fingolimod hydrochlorid;Fingolim Hydrochloride;Fingolimod hydrochloride(FTY720);Fingolimod,hydrochloride ( FTY720 , FTY-720A,Gilenia®,Gilenya®);2-Amino-2-[2-(4-n-octylphenyl)ethyl]propane-1,3-diol Hydrochloride;2-Amino-2-[2-(4-octyl-phenyl)-ethyl]-propane-1,3-diol hydrochloride;2-Amino-2-[2-(4-octyl-phenyl)-ethyl]-propane-1,3-diol hydrochloride Fingolimod hydrochloride;FTY-720;USD150;[ "FTY720", " Gilenya" ];Fin;FY720;Gilenya;FTY-720A;FTY720 . HCl;FTY720 B-0720;Unii-G926ec510t;FingoliMod FTY120;Gilenia;Fty 720;Fingolimod (FTY720) HCl;Fingolimod (hydrochloride);2-Amino-2-(2-(4-octylphenyl)ethyl)-1,3-propanediol hydrochloride;Fingolimod hydrochloride [USAN];G926EC510T;Gilenya (TN);2-AMINO-2-[2-(4-OCTYL-PHENYL)-ETHYL]-PROPANE-1,3-DIOL HCL;2-Amino-2
Cas No.	162359-56-0
分子式	C₁₉H₃₄ClNO₂
分子量	343.93
包装储存	4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

生物活性

Fingolimod hydrochloride (FTY720), an analog of sphingosine, is a potent sphingosine 1-phosphate (S1P) receptors modulator. Fingolimod hydrochloride is phosphorylated by sphingosine kinases, particularly by SK2, and then binds S1PR1, 3, 4, and 5. Fingolimod hydrochloride induces the internalization of S1P1, and consequently, inhibits S1P activity. Fingolimod hydrochloride also is a pak1 activator.

性状

Solid

IC50 & Target[1][2]

S1P

0.033 nM (IC₅₀, in K562 and NK cells)

PAK1

体外研究(In Vitro)

Fingolimod hydrochloride (FTY720) is a S1P antagonist with an IC₅₀ of 0.033 nM in K562 and NK cells.
The monocyte-derived immature dendritic cells (iDCs) are pretreated with various concentrations of S1P for various periods of time prior to their incubation with NK cells. Four hours incubation of autologous or allogeneic iDCs with 0.2-20 μM of S1P significantly protectes these cells from NK cell lysis. The IC₅₀ values of S1P are calculated at 160 nM for autologous iDCs, and 34 nM for allogeneic iDCs. Next, the inhibitory effect of S1P is revered by various concentrations of Fingolimod hydrochloride (FTY720) or SEW2871, with an IC₅₀ effect of 173 or 15 nM, respectively. The immunomodulator Fingolimod hydrochloride (FTY720) is a structural analogue of S1P and acts in its phosphorylated isoform as an unselective agonist on S1P₁ and S1P_3-5 and a selective functional antagonist on S1P₁.
FTY720 enhances serum S1P levels by inhibiting S1P lyase activity.
The number of Iba1 cells in ipsilateral CA3 is counted, and the corresponding graph shows a significantly lower number of Iba1 cells in CA3 of the Kainic acid (KA)+FTY720 group than in CA3 of KA group.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究(In Vivo)

Administration of the immunomodulator Fingolimod hydrochloride (0.1 mg/kg i.v.) increases serum S1P, improves impaired systolic contractility and activates the PI3K-pathway in the heart. Administration of Fingolimod hydrochloride (FTY720) causes a significant rise in serum S1P levels in both sham-operated animals and animals challenged with LPS/PepG (P<0.0001). FTY720 attenuates microgliosis, modulates the microglia inflammatory phenotype by reducing LPS-mediated activation of p38 MAPK signalling pathway. Thus, FTY720 shares both direct neuroprotective and anti-inflammatory properties that can contribute to overall neuroprotection. In particular, the potential of FTY720 to switch microglia phenotype from a detrimental to a protective one represents a therapeutic mechanism for attenuating acute and chronic CNS damage.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

运输条件

Room temperature or refrigerated transportation.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

ClinicalTrial

参考文献

[1]. Rolin J, et al. FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release. Cancer Immunol Immunother. 2010, 59(4), 575-586. [Information]

[2]. Coldewey SM, et al. Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. Sci Rep. 2016 Jun 9;6:27594. [Information]

[3]. Cipriani R, et al. FTY720 attenuates excitotoxicity and neuroinflammation. J Neuroinflammation. 2015 May 8;12:86. [Information]

[4]. Arielle M Bryan, et al. Sphingosine-1-phosphate receptors and innate immunity. Cell Microbiol. 2018 May;20(5):e12836. [Information]

溶解度数据

体外研究:

DMSO : ≥ 100 mg/mL (290.76 mM)

H₂O : 50 mg/mL (145.38 mM; Need ultrasonic)

* "≥" means soluble, but saturation unknown.

配制储备溶液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.9076 mL	14.5378 mL	29.0757 mL
5 mM	0.5815 mL	2.9076 mL	5.8151 mL
10 mM	0.2908 mL	1.4538 mL	2.9076 mL

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。

体内研究:

建议根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都建议先按照 体外研究 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

建议依照次序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (6.05 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (6.05 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH?O 中，得到澄清透明的生理盐水溶液
2.

建议依照次序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (6.05 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (6.05 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

建议依照次序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (6.05 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (6.05 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

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产品使用指南

Data Sheet

1：一般建议：溶解度为Medlife测试数据，可能与文献描述存在差异。这是由于生产工艺和批次不同产生的正常现象。为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同批次产品溶解度各有差异，仅做参考，具体以实验方案为准。

2：储存条件：粉末-20°C一般情况可以保存3年，溶于溶剂-80°C一般情况可以保存1年。不同产品及不同批次产品可能存在差异，请细致阅读产品信息，并辅助参考相关文献描述。

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