Fingolimod-FTY720-free-base-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFingolimodCat. No.: HY-11063CAS No.: 162359-55-9Synonyms: FTY720 free base分式: CHNO分量: 307.47作靶点: LPL Receptor; PAK作通路: GPCR/G Protein; Cell Cycle/DNA Damage; Cytoskeleton储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months

2、-20C 1 month溶解性数据体外实验 Methanol : 30 mg/mL (97.57 mM; Need ultrasonic)Ethanol : 7.69 mg/mL (25.01 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.2523 mL 16.2617 mL 32.5235 mL5 mM 0.6505 mL 3.2523 mL 6.5047 mL10 mM 0.3252 mL 1.6262 mL 3.2523 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注

3、意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% EtOH 40% PEG300 5% Tween-80 45% salineSolubility: 1 mg/mL (3.25 mM); Clear solution2. 请依序添加每种溶剂： 10% EtOH 90% (20% SBE-CD in saline)Solubility:

4、 1 mg/mL (3.25 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% EtOH 90% corn oilSolubility: 1 mg/mL (3.25 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Fingolimod种 1-磷酸鞘氨醇 (sphingosine 1-phosphate，S1P) 拮抗剂，作于 K562 和 NK 细胞，IC50为 0.033 nM。Fingolimod 还 种 pak1 激活剂。IC50

5、& Target S1P PAK10.033 nM (IC50, in K562 and NK cells)体外研究 The monocyte-derived immature dendritic cells (iDCs) are pretreated with various concentrations of S1P forvarious periods of time prior to their incubation with NK cells. Four hours incubation of autologous orallogeneic iDCs with 0.2-20 M of

6、 S1P significantly protectes these cells from NK cell lysis. The IC50 valuesof S1P are calculated at 160 nM for autologous iDCs, and 34 nM for allogeneic iDCs. Next, the inhibitoryeffect of S1P is revered by various concentrations of Fingolimod or SEW2871, with an IC50 effect of 173 or15 nM, respect

7、ively 1. Fingolimod has been reported to reduce LPA synthesis via inhibition of thelysophospholipase autotaxin. Fingolimod treatment correlates with a significant elevation of axonal cAMP, acrucial factor for axonal outgrowth. Additionally, Fingolimod significantly reduces LPA levels in the injuredn

8、erve. PF-8380 treatment correlates with improved myelin thickness 2.体内研究 Fingolimod treatment results in significantly increased nerve conduction at 14 days post-crush in wildtypeC57BL/6 mice. However, Foxn1-/- mice, which are devoid of T- but not B-lymphocytes, show animprovement of nerve regenerat

9、ion under fingolimod treatment. Although the mean increase in nerveconduction velocity in both fingolimod-treated and controlFoxn1-/- mice implies a potentially positive role of T-lymphocyte deficiency on nerve regeneration, only fingolimod-treated Foxn1-/- mice show a significantimprovement compare

10、d to C57BL/6 controls and performed better in the functional analysis 2. Treatment ofthe animals with Fingolimod for 28 d results in a clear reduction in the binding of 18F-GE180 when comparewith vehicle-treated animals and evaluated by ex vivo autoradiography. Quantification of the binding of thera

11、diotracer revealed a significant reduction in the binding potential of 18F-GE180 (P 3.PROTOCOLCell Assay 1 Immature dendritic cells (DCs) are left intact or are incubated with 2 M S1P, 10 nM Fingolimod, 10 nMSEW2871 or the combinations of S1P with these drugs for 4 h. As a control 1 g/mL LPS is used

12、. The cellsare washed and incubated in a 96-well plate (v-bottom, 2105 cells per well), washed again andresuspended in PBS buffer containing 0.1% sodium azide. They are labeled with 1 g/mL FITC-conjugatedmouse anti-human CD80, 1 g/mL FITC-conjugated mouse anti-human CD83, 1 g/mL FITC-conjugatedmouse

13、 anti-human CD86, 1 g/mL FITC-conjugated mouse anti-human HLA-class I, 1 g/mL FITC-conjugated mouse anti-human HLA-DR, 1 g/mL FITC-conjugated mouse anti-human HLA-E, or 1 g/mLFITC-conjugated mouse IgG as a control. The cells are washed twice, and examined in the flow cytometer.Markers are set accord

14、ing to the isotype control FITC-conjugated mouse IgG 1.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 23 Rag1-/- mice(B6.129S7-Rag1tm1Mom/J), Foxn1-/- mice (B6.Cg/NTac-Foxn1nu

15、) mice, and control C57BL/6mice are used. Mice receive non-phosphorylated Fingolimod via intraperitoneal injection at a concentration of1 mg/kg once daily over the course of 16 days, starting 2 days before crush until 14 days post-crush. PF-8380 is dissolved in DMSO and administered at a concentrati

16、on of 10 mg/kg via intraperitoneal injection oncedaily, as well starting 2 days before until 14 days post-crush. Controls receive an equal volume of solvent.Rats 3Male Lewis rats (50-100 g, n=18) are used. After the peripheral activation of the lesion, the DTH EAE lesionsare allowed to develop until

17、 day 127 to generate large chronic lesions and the animals are then treated for 28d with either Fingolimod (n=7) or vehicle (n=7). The Fingolimod treatment is given daily (0.3 mg/kg in 0.5 mLof water). The control group is given water (0.5 mL) as a vehicle control. The animals are dosed via oralgava

18、ge to ensure accurate dosing. In this model, the acute inflammation subsides after day 20 of activationof the lesion, and the BBB damage subsides. Thus, at day 127 the lesion clearly represents a well-developedchronic MS lesion. PET imaging is performed immediately before initiation of treatment and

19、 at the end of thetreatment period.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Haematologica. 2019 Jul 9. pii: haematol.2019.215939. Cancer Lett. 2018 Aug 16;436:75-86. Breast Cancer Res. 2017 Aug 4;19(1):90. Front Pharmacol. 2018 Oct 31

20、;9:1237. Front Endocrinol (Lausanne). 2018 Mar 22;9:120.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Rolin J, et al. FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells anddendritic cells but not on cytokine release. Cancer Immunol Immunother. 2010, 59(4), 575-586.2. Szepanowski F, et al. Fingolimod promotes peripheral nerve regenerat