Fludarabine

Catalog No.S1491 Batch:S149106

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Technical Data

Formula

C10H12FN5O4

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.)

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Biological Activity

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.
Targets
STAT1 [4]
(Vascular smooth muscle cells)
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].

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]

Protocol (from reference)

Cell Assay:

[1]

  • Cell lines

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

  • Concentrations

    2 μg/mL

  • Incubation Time

    24 hours

  • Method

    After treated with Fludarabine or control, dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) human MM cell lines, RPMI8226 and U266 cell lines (5 × 105 cells) are washed twice in phosphate-buffered saline (PBS) and fixed with 70% ice-cold ethanol, then centrifuged and suspended in PBS containing 100 μg/mL RNase A. After incubated for 30 minutes at 37 ºC, samples are resuspended in 25 μg/mL propidium iodide. Flow cytometry is performed on a FACSCalibur automated system. Apoptosis is determined by Annexin V-FITC apoptosis detection kit, according to the manufacturer's instructions. For TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) assay, cells are analyzed by flow cytometry using the in situ cell death detection kit.

Animal Study:

[1]

  • Animal Models

    Severe combined immunodeficient (SCID) mice bearing RPMI 8226 cells

  • Dosages

    40 mg/kg

  • Administration

    Administered via i.p.

Customer Product Validation

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 ]

Selleck's Fludarabine has been cited by 188 publications

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
Lnc-CCNH-8 promotes immune escape by up-regulating PD-L1 in hepatocellular carcinoma [ Mol Ther Nucleic Acids, 2024, 35(1):102125] PubMed: 38356866
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
ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells [ Int J Mol Sci, 2024, 25(4)2408] PubMed: 38397085
CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress [ Drug Resist Updat, 2023, 71:101015] PubMed: 37924725
The STAT1/HMGB1/NF-κB pathway in chronic inflammation and kidney injury after cisplatin exposure [ Theranostics, 2023, 13(9):2757-2773] PubMed: 37284446
Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1 [ J Exp Clin Cancer Res, 2023, 10.1186/s13046-023-02872-1] PubMed: 37968723
Tumor-secreted IFI35 promotes proliferation and cytotoxic activity of CD8+ T cells through PI3K/AKT/mTOR signaling pathway in colorectal cancer [ J Biomed Sci, 2023, 30(1):47] PubMed: 37380972

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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