Fludarabine phosphate
[CAS# 75607-67-9]

Identification

• Classification: API >> Antineoplastic agents >> Antimetabolite antineoplastic
• Name: Fludarabine phosphate
• Synonyms: 9-bata-D-Arabinofuranosyl-2-fluoroadenine phosphate
• Molecular Formula: C₁₀H₁₃FN₅O₇P
• Molecular Weight: 365.21
• Protein Sequence: N
• CAS Registry Number: 75607-67-9
• EC Number: 616-242-0
• SMILES: C1=NC2=C(N=C(N=C2N1[C@H]3[C@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O)F)N

Properties

• Solubility: 10 mM (H2O) (Expl.)
• Density: 2.4±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.879, Calc.^*
• Boiling Point: 864.2±75.0 °C (760 mmHg), Calc.^*
• Flash Point: 476.4±37.1 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Dander
• Risk Statements: H341-H350-H360-H361-H372
• Safety Statements: P203-P260-P264-P270-P280-P318-P319-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Germ cell mutagenicity	Muta.	2	H341
Reproductive toxicity	Repr.	2	H361
Reproductive toxicity	Repr.	1B	H360
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Carcinogenicity	Carc.	1B	H350
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Lact.	-	H362
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

Fludarabine phosphate is a purine analog and an important chemotherapy agent used in the treatment of various cancers, particularly hematologic malignancies. It was first synthesized in the 1970s by researchers seeking to develop compounds that could inhibit DNA synthesis. The compound is a prodrug, meaning that it requires metabolic activation within the body to exert its therapeutic effects. Once administered, fludarabine phosphate is converted into its active form, fludarabine, which incorporates into DNA and disrupts the replication process, leading to cell death.

Fludarabine phosphate gained approval for clinical use in the United States in the late 1990s for the treatment of chronic lymphocytic leukemia (CLL), a type of cancer that affects the white blood cells. Since then, it has been used for the treatment of other cancers, including non-Hodgkin lymphoma and certain forms of leukemia. Its mechanism of action makes it particularly effective in cancers that involve rapidly dividing cells.

The drug has been studied extensively in clinical trials and has been shown to be effective as part of combination chemotherapy regimens. It is often used in combination with other agents such as cyclophosphamide and rituximab to enhance its efficacy and manage resistance mechanisms that may arise during treatment. Fludarabine phosphate has also been investigated in stem cell transplantation and as part of conditioning regimens to prepare patients for bone marrow transplants.

Despite its effectiveness, fludarabine phosphate can cause side effects such as immunosuppression, which increases the risk of infections, and hematologic toxicities like low blood counts. The drug's use is carefully monitored, especially in elderly patients and those with pre-existing kidney issues. Researchers continue to explore its potential in combination with newer therapies and in the treatment of other cancers.

References

2003. Subcutaneous panniculitis-like T-cell lymphoma: complete remission with fludarabine. Annals of Hematology, 82(3).
DOI: 10.1007/s00277-003-0638-9

2003. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Annals of Hematology, 82(4).
DOI: 10.1007/s00277-003-0624-2

2000. Induction of apoptosis using 2',2'difluorodeoxycytidine (gemcitabine) in combination with antimetabolites or anthracyclines on malignant lymphatic and myeloid cells. Antagonism or synergism depends on incubation schedule and origin of neoplastic cells. Annals of Hematology, 79(9).
DOI: 10.1007/s002770000181