Fludarabine

2 years -80 in solvent

Administered via i.p.

Dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) human MM cell lines, RPMI8226 and U266 cell lines

40 mg/kg

Fludarabine efficiently inhibits the proliferation of RPMI 8226 cells with IC50 of 1.54 ug/mL. The IC50 of Fludarabine against MM.1S and MM.1R cells is 13.48 ug/mL and 33.79 ug/mL, respectively. In contrast, U266 cells are resistant to Fludarabine with IC50 of 222.2 ug/mL. Fludarabine treatment results in increased number of cells in the G1 phase of cell cycle, accompanied with a concomitant reduction of cells at the S phase of cell cycle in a time-dependent manner. Fludarabine induces a cell cycle block and triggers apoptosis in MM cells. Fludarabine triggers time-dependent cleavage of caspase-8, -9, and -3, -7, followed by PARP cleavage. Fludarabine increases expression of Bax in a time-dependent fashion, while the expression of Bak doesn't change. After exposure to Fludarabine for 12 hours, RPMI 8226 cells shows a loss of membrane potential with 61.05% of the cells expressing low fluorescence of rhodamine 123 compared with 8.62% of cells in untreated control. [1] To enhance solubility, Fludarabine is formulated as the monophosphate (F-ara-AMP, fudarabine), which is instantaneously and quantitatively dephosphorylated to the parent nucleoside upon intravenous infusion. Inside the cells rephosphorylation occurs which leads to fuoroadenine arabinoside triphosphate (F-ara-ATP), the major cytotoxic metabolite of F-ara-A. [2] Fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased expression of ICAM-1 and IL-8 release. [3] Fludarabine does not affect the growth of ovarian cancer cell lines, whereas it induces marked and dose-dependent inhibition of proliferation in melanoma cell lines. [4] Fludarabine induces significant reduction of STAT-1 phosphorylation, whereas it does not change JAK2 activation. Interestingly, Fludarabine does not significantly affect the phosphorylation of these three STAT proteins. Fludarabine (1.5 mg) significantly prevents STAT-1 phosphorylation and also reduces the increased amount of this protein. No significant changes are demonstrated in JAK2 phosphorylation at 2 days, but Fludarabine inhibits JAK2-increased expression at 7 days. Fludarabine specifically inhibits STAT-1 activation without affecting other STAT proteins and consequently diminishes VSMC proliferation. [5]

24 hours

DMSO 57 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL

(2R, 3S, 4S, 5R)-2-(6-amino-2-fluoro-9H-purin-9-yl)-5-(hydroxymethyl)-tetrahydrofuran-3, 4-diol