product name Fludarabine Phosphate
Description: Fludarabine phosphate [also known as F-ara-A (NSC 312887) Phosphate] is a potent STAT-1 activation inhibitor and a DNA synthesis inhibitor. Fludarabine phosphate is the phosphate salt of a fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP.
References: J Biol Chem. 1990 Sep 25;265(27):16617-25; Cancer Res. 1982 Jul;42(7):2587-91.
365.21
Formula
C10H13FN5O7P
CAS No.
75607-67-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 73 mg/mL (199.9 mM)
Water: 2 mg/mL (5.5 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
F-ara-A (NSC 312887) Phosphate
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19413546
| In Vitro |
In vitro activity: Fludarabine Phosphate is converted to F-ara-ATP in cells and then incorporated into DNA in a self-limiting manner. Fludarabine Phosphate competes with dATP for incorporation into the A site of the extending DNA strand, which results in termination of DNA strand elongation. Human DNA polymerase α incorporates more Fludarabine Phosphate into DNA than polymerase δ. Fludarabine Phosphate completively inhibits DNA polymerase α and DNA polymerase δ with Ki of 1.1 μM and 1.3 μM, respectively. DNA polymerase δ is also able to excise the incorporated Fludarabine Phosphate from DNA in vitro. Kinase Assay: Cell Assay: Cells (Human T lymphoblastoid cells) are incubated with Fludarabine Phosphate for 5 hr and washed twice with drug-free warm medium. 800 cells are mixed with 1.3 mL of 0.25% soft agar in Dulbecco’s medium supplemented with 20% fetal bovine serum (pre-warmed to 37 ℃) and incubated in a tissue culture dish for 10 days (humidified 5% CO2 , 37 ℃). At the end of the incubation period, colonies of more than 40 cells are scored under a microscope. The cytotoxic effect of the drugs is expressed as a percentage of survival relative to that of untreated control cells. |
|---|---|
| In Vivo | Fludarabine Phosphate is toxic for tumor-free mice. The maximum tolerated dose (LD10) Fludarabine Phosphate administered as a single dose is 234 mg/kg. The 50% lethal dose is 375 mg/kg. Fludarabine Phosphate administered as a single dose induces fewer number of cells surviving therapy in mice bearing P388 leukemia, accompanied by greater percentage of increase in life span (110%) and increased median survival time. |
| Animal model | Murine Leukemia P3881 |
| Formulation & Dosage | Dissolved in water; 234 mg/kg; i.p. injection |
| References | J Biol Chem. 1990 Sep 25;265(27):16617-25; Cancer Res. 1982 Jul;42(7):2587-91. |
