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Formula | C10H12FN5O4 |
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Molecular Weight | 285.23 | CAS No. | 21679-14-1 | |
Solubility (25°C)* | In vitro | DMSO | 57 mg/mL (199.83 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Fludarabine is a STAT1 activation inhibitor which causes a specific depletion of STAT1 protein (and mRNA) but not of other STATs. Also a DNA synthesis inhibitor in vascular smooth muscle cells. Fludarabine induces apoptosis. | |
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In vitro | Fludarabine efficiently inhibits the proliferation of RPMI 8226 cells with IC50 of 1.54 μg/mL. The IC50 of Fludarabine against MM.1S and MM.1R cells is 13.48 μg/mL and 33.79 μg/mL, respectively. In contrast, U266 cells are resistant to Fludarabine with IC50 of 222.2 μg/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 is an inhibitor of STAT1 that specifically reduces STAT1 without affecting other STAT family members[5]. In addition to cytoplasmic accumulation, repeated low-dose cisplatin (RLDC) induces HMGB1 expression, which is marked suppressed by STAT1 knockdown. Consistently, fludarabine suppresses HMGB1 expression during RLDC treatment dose-dependently in RLDC-treat renal tubular cells[5]. |
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In vivo | Tumors treated with PBS grow rapidly to approx-imately 10-fold their initial volume in 25 day, whereas, the tumors in the Fludarabine at 40 mg/kg increase less than 5-fold. A significant antitumor effect of 40 mg/kg Fludarabine on RPMI8226 tumor growth is demonstrated. RPMI8226 tumors treated with 40 mg/kg Fludarabine at day 10 increase apoptotic nuclei. Fludarabine is effective in suppressing RPMI8226 myeloma xenografts in SCID mice. [1] |
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Data from [Data independently produced by Mol Cell Biol, 2014, 34(24), 4368-78.]
Data from [Data independently produced by , , Br J Cancer, 2018, 118(4):509-521]
Data from [Data independently produced by , , Brain Behav Immun, 2017, 60:161-173]
Data from [Data independently produced by , , Mol Cancer Ther, 2014, 13(10): 2276-87 ]
Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice [ Nat Commun, 2024, 15(1):1718] | PubMed: 38409097 |
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer [ Cell Rep Med, 2024, 5(2):101420] | PubMed: 38382468 |
The involvement of the Stat1/Nrf2 pathway in exacerbating Crizotinib-induced liver injury: implications for ferroptosis [ Cell Death Dis, 2024, 15(8):600] | PubMed: 39160159 |
Lnc-CCNH-8 promotes immune escape by up-regulating PD-L1 in hepatocellular carcinoma [ Mol Ther Nucleic Acids, 2024, 35(1):102125] | PubMed: 38356866 |
The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia [ Blood Adv, 2024, 8(20):5315-5329] | PubMed: 39093953 |
Paradoxical cancer cell proliferation after FGFR inhibition through decreased p21 signaling in FGFR1-amplified breast cancer cells [ Breast Cancer Res, 2024, 26(1):54] | PubMed: 38553760 |
IL-35 Stabilizes Treg Phenotype to Protect Cardiac Allografts in Mice [ Transplantation, 2024, 108(1):161-174] | PubMed: 37464473 |
IL-35 Stabilizes Treg Phenotype to Protect Cardiac Allografts in Mice [ Transplantation, 2024, 108(1):161-174] | PubMed: 37464473 |
Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation [ Commun Biol, 2024, 7(1):370] | PubMed: 38538870 |
Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation [ Commun Biol, 2024, 7(1):370] | PubMed: 38538870 |
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