Basic information
- Standard SMILES
Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)O)[C@@H](O)[C@@H]1O- InChIKey
GIUYCYHIANZCFB-FJFJXFQQSA-N- Molecular formula
- C10H13FN5O7P
- Average molar mass
- 365.21 g/mol
- Monoisotopic mass
- 365.05366261
Overview
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 antiviral agent, an antimetabolite, an antineoplastic agent, an immunosuppressive agent, a prodrug and a DNA synthesis inhibitor. It is an organofluorine compound, a purine arabinonucleoside monophosphate and a nucleoside analogue. It is functionally related to a 2-fluoroadenine.
Names & identifiers
- Preferred name
- Fludarabine Phosphate
- IUPAC
- [(2R,3S,4S,5R)-5-(6-amino-2-fluoropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Names & synonyms
fludarabine phosphate75607-67-9fludaraFludarabine 5'-monophosphateOfortaFludarabine monophosphate2-F-ara-AMPNSC-3128872-Fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl)-9H-purin-6-amine1X9VK9O1SCNSC 312887CHEBI:63599
Show more names
2F-ara-AMPNSC-3280029-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphate)DTXSID20230609H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl)-F-ara-AMPFaraAMPfluoro-ara-AMP
Database identifiers
- CAS
75607-67-9- PubChem CID
- 30751
- DTXSID
DTXSID2023060- ChEMBL
CHEMBL1096882- ChEBI
CHEBI:63599- UNII
- 1X9VK9O1SC
- EC Number
- 616-242-0
- Nikkaji
- J535.382C
Properties
Computed structural properties
- XLogP
- -3.1
- Topological polar surface area
- 186 Ų
- Hydrogen bond donors
- 5
- Hydrogen bond acceptors
- 12
- Rotatable bonds
- 4
- Heavy atoms
- 24
- Formal charge
- 0
- Complexity
- 514
Experimental & physicochemical properties
LogP-2.8
Solubility
2.97e+00 g/L
Water 9.2 (mg/mL)
pH 4 buffer 27.6 (mg/mL)
pH 9 buffer 57 (mg/mL)
Human Drugs
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Melting Point260 °C
Optical Rotation(c = 0.5, H2O) [a]21D = 12 ± 2°
Physical DescriptionSolid
Stability/Shelf Life
Bulk: Based on HPLC analysis, the sample is stable for at least one month when stored as the bulk chemical at room temperature and 60 °C. Solution: A 2 mg/mL aqueous solution is stable for at least 48 hours at room temperature and laboratory illumination (HPLC).
Collision Cross Section168.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Safety & regulation
GHS classification
GHS Classification
Danger
H341 (97.6%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]
P203, P260, P264, P270, P280, P318, P319, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 82 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard information
Hazard Classes and CategoriesMuta. 2 (97.6%)
Toxicology
Exposure RoutesBioavailability is 55% following oral administration.
Toxicity Summary
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.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury
Drug Induced Liver Injury Rank (DILIrank 2.0)
Fludarabine phosphate
vNo-DILI-concern
0
No match
DOI:10.1016/j.drudis.2016.02.015
Toxicity DataMouse(iv): LD50: 1236 mg/kg
Chemistry & industry
Pharmacology
Metabolism/MetabolitesHalf Life: 20 hours
FDA Pharmacological Classification
FLUDARABINE PHOSPHATE
Nucleoside Metabolic Inhibitor [EPC]; Nucleic Acid Synthesis Inhibitors [MoA]
MeSH Pharmacological Classification
Antimetabolites that are useful in cancer chemotherapy.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
Cellular LocationsCytoplasm
Uses & manufacturing
UsesFor 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 regimen
Related reactions
4 records
Linked notes
Loading…