Fingolimod (FTY720) HCl

343, 9

NOD/SCIDgammac / mice bearing ALL cells.

FTY720 has enterd in a phase IV clinical trial in the treatment of multiple sclerosis anbd relapsing-remitting.

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

0.033 nM [1], 0.033 nM [1], 0.033 nM [1], 0.033 nM [1], 0.033 nM [1], 0.033 nM [1]

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+/-12% 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. [3]

Immature DCs are left intact or are incubated with 2 uM S1P, 10 nM FTY720, 10 nM SEW2871 or the combinations of S1P with these drugs for 4 hours. As a control 1 ug/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 ug/mL FITC-conjugated mouse anti-human CD80, 1 ug/mL FITC-conjugated mouse anti-human CD83, 1 ug/mL FITC-conjugated mouse anti-human CD86, 1 ug/mL FITC-conjugated mouse anti-human HLA-class I, 1 ug/mL FITC-conjugated mouse anti-human HLA-DR, 1 ug/mL FITC-conjugated mouse anti-human HLA-E, or 1 ug/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 uM S1P for 4 hours, washed and stained with 1 ug/mL PE-conjugated mouse anti-human NKp30 (CD337), 1 ug/mL PE-conjugated mouse anti-human NKp44 (CD336), 1 ug/mL PE-conjugated mouse anti-human NKG2D (CD314), or as a control 1 ug/mL PE-conjugated mouse IgG1, for 45 min at 4 C. NK cells are also stained with 1 ug/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.

Fingolimod (FTY720, Fingolimod Hydrochloride) HCl is a S1P antagonist with IC50 of 0.033 nM in K562, and NK cells. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation.