Fingolimod-hydrochloride-FTY720-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFingolimod hydrochlorideCat. No.: HY-12005CAS No.: 162359-56-0Synonyms: FTY720分式: CHClNO分量: 343.93作靶點(diǎn): LPL Receptor; PAK作通路: GPCR/G Protein; Cell Cycle/DNA Damage; Cytoskeleton儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6

2、months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (290.76 mM)H2O : 50 mg/mL (145.38 mM; Need ultrasonic)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.9076 mL 14.5378 mL 29.0757 mL5 mM 0.5815 mL 2.9076 mL 5.8151 mL10 mM 0.2908 mL 1.4538 mL 2.9076 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑

3、中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Fingolimod hydrochloride是鞘氨醇1-磷酸 (S1P)拮抗劑，在K562和NK細(xì)胞中的IC50 為0.033 nM。Fingolimod hydrochloride 還 種 pak1 激活劑。IC50 & Target S1P PAK11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE0.033 nM (IC50, in K562 and NK cells)體外研究 The monocyte-derived im

4、mature 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 S1P significantly protectes these cells from NK cell lysis. The IC50 valuesof S1P

5、 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 hydrochloride (FTY720) or SEW2871, withan IC50 effect of 173 or 15 nM, respectively 1. The immunomodulator Fingolimod hydrochloride (FTY7

6、20) isa structural analogue of S1P and acts in its phosphorylated isoform as an unselective agonist on S1P1 andS1P3-5 and a selective functional antagonist on S1P1. FTY720 enhances serum S1P levels by inhibitingS1P lyase activity 2. The number of Iba1+ cells in ipsilateral CA3 is counted, and the co

7、rresponding graphshows a significantly lower number of Iba1+ cells in CA3 of the Kainic acid (KA)+FTY720 group than in CA3of KA group 3.體內(nèi)研究 Administration of the immunomodulator Fingolimod hydrochloride (0.1 mg/kg i.v.) increases serum S1P,improves impaired systolic contractility and activates the

8、PI3K-pathway in the heart. Administration ofFingolimod hydrochloride (FTY720) causes a significant rise in serum S1P levels in both sham-operatedanimals and animals challenged with LPS/PepG (P 2. FTY720 attenuates microgliosis, modulates themicroglia inflammatory phenotype by reducing LPS-mediated a

9、ctivation of p38 MAPK signalling pathway.Thus, FTY720 shares both direct neuroprotective and anti-inflammatory properties that can contribute tooverall neuroprotection. In particular, the potential of FTY720 to switch microglia phenotype from adetrimental to a protective one represents a therapeutic

10、 mechanism for attenuating acute and chronic CNSdamage 3.PROTOCOLCell Assay 1 Immature dendritic cells (DCs) are left intact or are incubated with 2 M S1P, 10 nM Fingolimodhydrochloride, 10 nM SEW2871 or the combinations of S1P with these drugs for 4 h. As a control 1 g/mLLPS is used. The cells are

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

12、D86, 1 g/mL FITC-conjugated mouse anti-human HLA-class I, 1 g/mLFITC-conjugated mouse anti-human HLA-DR, 1 g/mL FITC-conjugated mouse anti-human HLA-E, or 1 g/mL FITC-conjugated mouse IgG as a control. The cells are washed twice, and examined in the flowcytometer. Markers are set according to the is

13、otype control FITC-conjugated mouse IgG 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 23 This study is carried out on 2-month-old male C57BL/6J mice or sphingosine kinase-2 deficient (SPHK-2-/-)mice weighing 25-30 g, rece

14、iving a standard diet and water ad libitum. C57BL/6J wild-type or SPHK-2-/- micereceives i.p.-injections of LPS (9 mg/kg)/PepG (1 mg/kg) or its vehicle (0.9% saline). Sham mice are notsubjected to LPS/PepG, but are otherwise treated in the same way. At 1 h after LPS/PepG challenge, miceare treated w

15、ith Fingolimod hydrochloride (0.1 mg/kg i.v.) or its vehicle (10% DMSO). To elucidate the role of2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEdifferent S1P receptors in the observed effects of Fingolimod hydrochloride, mice receive (45 min afterLPS/PepG and 15 min prior to Fingolimod hydrochlori

16、de) the selective PI3K inhibitor LY294002 (0.3 mg/kgi.v.) or the selective S1P2 receptor antagonist JTE 013 (1 mg/kg i.v.) or (1 h after LPS/PepG) the selectiveS1P1 receptor agonist SEW2871 (1 mg/kg i.v.) or vehicle (10% DMSO).Rat 3The Sprague-Dawley rats (200 to 250 g) are used. Fingolimod hydrochl

17、oride is applied icv (1 g/2 L),together with Kainic acid (KA), plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 daysaftericv. Rats are evaluated for neurological score, neuronal loss in CA3 hippocampal region and activationof microglia at the lesion site.MCE has not ind

18、ependently confirmed the accuracy of these methods. They are for reference only.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) 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;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