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Fludarabine phosphate

CAS No.75607-67-9
Chemical Name:Fludarabine phosphate
CBNumber:CB7347825
Molecular Formula:C10H13FN5O7P
Formula Weight:365.21
MOL File:75607-67-9.mol

Fludarabine phosphate Property

Melting point 203°C(dec.)(lit.)
alpha [α]D20 +10～+14゜(c=0.5,H2O)
Boiling point 864.2±75.0 °C(Predicted)
Density 2.39±0.1 g/cm3(Predicted)
RTECS UO7440900
storage temp. 2-8°C
solubility DMSO: soluble1mg/mL
pka 1.86±0.10(Predicted)
form Powder
color white
Water Solubility Soluble in DMSO or water at 5mg/ml
Merck 14,4126
Stability Hygroscopic
InChIKey GIUYCYHIANZCFB-GFRUICAKSA-N
CAS DataBase Reference 75607-67-9(CAS DataBase Reference)
NCI Dictionary of Cancer Terms fludarabine phosphate
FDA UNII 1X9VK9O1SC
NCI Drug Dictionary fludarabine phosphate
UNSPSC Code 51102829
NACRES NA.85

Safety

WGK Germany :3
HS Code :2934990002

NFPA 704:

	0
2		0

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal wordWarning
Hazard statements H341-H361d
Precautionary statements P201-P202-P280-P308+P313-P405-P501

Fludarabine phosphate Price More Price(4)

Brand: Sigma-Aldrich(India)
Product number: F9813
Product name : Fludarabine phosphate
Purity:
Packaging: 5MG
Price: ₹5542.4
Updated: 2022/06/14
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Brand: Sigma-Aldrich(India)
Product number: F9813
Product name : Fludarabine phosphate
Purity:
Packaging: 25MG
Price: ₹21206.18
Updated: 2022/06/14
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Brand: TCI Chemicals (India)
Product number: F0913
Product name : Fludarabine Monophosphate
Purity:
Packaging: 25MG
Price: ₹2500
Updated: 2022/05/26
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Brand: TCI Chemicals (India)
Product number: F0913
Product name : Fludarabine Monophosphate
Purity:
Packaging: 100MG
Price: ₹8200
Updated: 2022/05/26
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Fludarabine phosphate Chemical Properties,Usage,Production

Description Fludarabine phosphate is an antimetabolite indicated for the treatment of B cell lymphocytic leukemia. It is reportedly effective in patients refractory to other therapies. Fludarabine phosphate acts by inhibiting primer RNA synthesis. Its side effects include bone marrow suppression, anemia, thrombocytopenia and neutropenia.
Chemical Properties White or almost white, crystalline powder, hygroscopic.
Originator Southern Research Institute (U.S.A.)
Uses Fludarabine phosphate is used for the treatment of chronic lymphatic leukemia and low-grade lymphoma. In the circulation,fludarabine phosphate is immediately dephosphorylated to the nucleoside fludarabine. About 30-40% of nucleoside fludarabine is excreted into the urine. In addition, fludarabine is metabolized into a hypoxanthine metabolite also excreted in the urine.Intracellularly,fludarabine is stepwise rephosphorylated to the active triphosphate. Deoxycytidine kinase is the dominant, if not the exclusive,enzyme for the formation of the monophosphate. Adenylate kinase and nucleoside diphosphate kinase are believed to be involved in the formation of the diphosphate and triphosphate,respectively.
Uses anticonvulsant
Definition ChEBI: Fludarabine phosphate is a purine arabinonucleoside monophosphate having 2-fluoroadenine as the nucleobase. A prodrug, it is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. Once incorporated into DNA, 2-fluoro-ara-ATP functions as a DNA chain terminator. It is used for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to, or whose disease has progressed during, treatment with at least one standard alkylating-agent containing regimenas. It has a role as an antimetabolite, an antineoplastic agent, an immunosuppressive agent, an antiviral agent, a prodrug and a DNA synthesis inhibitor. It is an organofluorine compound, a nucleoside analogue and a purine arabinonucleoside monophosphate. It derives from a 2-fluoroadenine.
brand name Fludara (Berlex), Benefluor (Schering AG).
Mechanism of action Fludarabine phosphate is a cytotoxic purine antimetabolite that acts by inhibiting DNA synthesis. Fludarabine and its soluble derivatives interfere with phosphorylation, e.g., in L 1210 cells. Fludarabine behaves more like an analog of deoxycytidine than adenine or deoxyadenine as indicated by reports demonstrating that the presence of fluorine in the 2-position of the adenine ring alters its function as a substrate for deaminase and nucleoside kinases. This results in differences in biological activity and metabolism. Halogenation does not simply block deamination, but also influences the enzyme that carries out the phosphorylation, as a result cytotoxicity is increased. Fludarabine phosphate may selectively inhibit the incorporation of thymidine and uridine into the DNA molecule by inhibiting both ribonucleotide reductase and DNA polymerase. The maximum tolerated dose (MTD) in heavily pretreated patients with advanced malignancy/solid tumors on the daily regimen was about 15 mg/m2. Granulocytopenia and thrombocytopenia were dose-limiting.
Pharmacology 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. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Phase I studies in humans have demonstrated that fludarabine phosphate is rapidly converted to the active metabolite, 2-fluoro-ara-A, within minutes after intravenous infusion.
Consequently, clinical pharmacology studies have focused on 2-fluoro-ara-A pharmacokinetics. After the five daily doses of 25 mg 2-fluoro-ara-AMP/m2 to cancer patients infused over 30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation. During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A was estimated as approximately 20 hours. In vitro, plasma protein binding of fludarabine ranged between 19% and 29%.
Clinical Use Fludarabine phosphate (Fludara ® ), is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine(ara-A), which differs only by the presence of a fluorine atom at position 2 of the purine moiety and a phosphate group at position 5 of the arabinose moiety (Plunkett et al., 1993). These structural modifications result in increased aqueous solubility and resistance to enzymatic degradation by adenosine deaminases compared to vidarabine (Brockman et al., 1977; Plunkett et al., 1990). Fludarabine phosphate is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating agent containing regimen (Boogaerts et al., 2001; Rossi et al., 2004).
target DNA synthesis
Drug interactions Potentially hazardous interactions with other drugs
Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis.
Cytotoxics: increased pulmonary toxicity with pentostatin (unacceptably high incidence of fatalities); increases intracellular concentration of cytarabine.
Metabolism Intravenous fludarabine phosphate is rapidly dephosphorylated to fludarabine which is taken up by lymphocytes and rephosphorylated via the enzyme deoxycytidine kinase to the active triphosphate nucleotide. Clearance of fludarabine from the plasma is triphasic; elimination is mostly via renal excretion: 40-60% of an intravenous dose is excreted in the urine. The pharmacokinetics of fludarabine show considerable inter-individual variation