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Fludarabine Phosphate

PubChem CID
30751
Structure
Fludarabine Phosphate_small.png
Fludarabine Phosphate_3D_Structure.png
Molecular Formula
Synonyms
  • fludarabine phosphate
  • 75607-67-9
  • fludara
  • Fludarabine 5'-monophosphate
  • Oforta
Molecular Weight
365.21 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-25
Description
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 is functionally related to a 2-fluoroadenine.
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. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth.
FLUDARABINE PHOSPHATE is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 1991 and has 3 approved and 138 investigational indications. This drug has a black box warning from the FDA.
See also: Fludarabine (has active moiety).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Fludarabine Phosphate.png

1.2 3D Conformer

2 Biologic Description

IUPAC Condensed
P-fl2Ade-Araf
Sequence
N
IUPAC
5'-phosphono-(2'S)-2-fluoro-adenosine

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

[(2R,3S,4S,5R)-5-(6-amino-2-fluoropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C10H13FN5O7P/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(18)5(17)3(23-9)1-22-24(19,20)21/h2-3,5-6,9,17-18H,1H2,(H2,12,14,15)(H2,19,20,21)/t3-,5-,6+,9-/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

GIUYCYHIANZCFB-FJFJXFQQSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 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
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C10H13FN5O7P
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

3.3.2 European Community (EC) Number

3.3.3 UNII

3.3.4 ChEBI ID

3.3.5 ChEMBL ID

3.3.6 DSSTox Substance ID

3.3.7 HMDB ID

3.3.8 KEGG ID

3.3.9 NCI Thesaurus Code

3.3.10 Nikkaji Number

3.3.11 NSC Number

3.3.12 PharmGKB ID

3.3.13 Pharos Ligand ID

3.3.14 RXCUI

3.3.15 Wikidata

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • 9 beta-D-arabinofuranosyl-2-fluoroadenine monophosphate
  • 9H-purin-6-amine, 2-fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl)-
  • Beneflur
  • F-ara-AMP
  • FaraAMP
  • Fludara
  • fludarabine 5'-monophosphate
  • fludarabine monophosphate
  • fludarabine phosphate
  • fluoro-ara-AMP
  • NSC 312887
  • NSC-312887

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
365.21 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-3.1
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
12
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
365.05366293 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
365.05366293 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
186 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
24
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
514
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
4
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

4.2 Experimental Properties

4.2.1 Physical Description

Solid

4.2.2 Melting Point

260 °C

4.2.3 Solubility

2.97e+00 g/L
Water 9.2 (mg/mL)
pH 4 buffer 27.6 (mg/mL)
pH 9 buffer 57 (mg/mL)

4.2.4 LogP

-2.8

4.2.5 Stability / Shelf Life

Stability
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).

4.2.6 Optical Rotation

(c = 0.5, H2O) [a]21D = 12 ± 2°

4.2.7 Collision Cross Section

168.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

4.3 Chemical Classes

4.3.1 Drugs

4.3.1.1 Human Drugs
Human drug -> Discontinued
Human drug -> Prescription; Discontinued; Active ingredient (FLUDARABINE PHOSPHATE)

5 Spectral Information

5.1 UV Spectra

(0.1 N HCl) max = 262 ± 2 nm E = 12,600 - 13,400

5.2 Chromatograms

5.2.1 HPLC

HPLC
Column: Alltech ODS, 250 x 4.6 mm i.d. Mobile Phase: 5% MeOH in 0.1 M KH buffer, pH 4 Flow Rate: 1.5 mL/min Detection: UV at 254 nm Sample Preparation: 0.2 mg/mL in internal standard solution Internal Standard: 0.3 mg thymidine/mL water Retention Volume: 13.0 mL (NSC-312887) 19.5 mL (I.S.)

7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

8.2 FDA Approved Drugs

8.3 FDA Orange Book

8.4 FDA National Drug Code Directory

8.5 Drug Labels

Drug and label
Active ingredient and drug

8.6 Cancer Drugs

Drug Name
Fludarabine Phosphate
FDA Approved
Yes
Drug Use

Fludarabine phosphate is approved to treat adults with:

• B-cell chronic lymphocytic leukemia (CLL). It is used as part of combination therapy for B-cell CLL or alone for B-cell ALL that did not get better or got worse during at least one other treatment that included an alkylating agent.

Fludarabine phosphate is also being studied in the treatment of other types of cancer.

8.7 Clinical Trials

8.7.1 ClinicalTrials.gov

8.7.2 EU Clinical Trials Register

8.7.3 NIPH Clinical Trials Search of Japan

9 Pharmacology and Biochemistry

9.1 MeSH Pharmacological Classification

Antimetabolites, Antineoplastic
Antimetabolites that are useful in cancer chemotherapy. (See all compounds classified as Antimetabolites, Antineoplastic.)
Immunosuppressive Agents
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. (See all compounds classified as Immunosuppressive Agents.)

9.2 FDA Pharmacological Classification

Non-Proprietary Name
FLUDARABINE PHOSPHATE
Pharmacological Classes
Nucleic Acid Synthesis Inhibitors [MoA]; Nucleoside Metabolic Inhibitor [EPC]

9.3 Metabolism / Metabolites

Half Life: 20 hours

9.4 Human Metabolite Information

9.4.1 Cellular Locations

  • Cytoplasm
  • Membrane

10 Use and Manufacturing

10.1 Uses

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 regimen

10.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Health Hazard
Signal
Danger
GHS Hazard Statements

H341 (97.5%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H350 (29.6%): May cause cancer [Danger Carcinogenicity]

H360 (33.3%): May damage fertility or the unborn child [Danger Reproductive toxicity]

H361 (66.7%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H372 (29.6%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

Precautionary Statement Codes

P203, P260, P264, P270, P280, P318, P319, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 81 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Muta. 2 (97.5%)

Carc. 1B (29.6%)

Repr. 1B (33.3%)

Repr. 2 (66.7%)

STOT RE 1 (29.6%)

12 Toxicity

12.1 Toxicological Information

12.1.1 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.

12.1.2 Carcinogen Classification

Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

12.1.3 Exposure Routes

Bioavailability is 55% following oral administration.

12.1.4 Acute Effects

12.1.5 Toxicity Data

ToxicityData
Mouse(iv): LD50: 1236 mg/kg
National Technical Information Service, PB83- 195685

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Chemical Co-Occurrences in Literature

14.5 Chemical-Gene Co-Occurrences in Literature

14.6 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Chemical-Target Interactions

17 Biological Test Results

17.1 BioAssay Results

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: Drug

18.5 KEGG: USP

18.6 KEGG: ATC

18.7 KEGG: Target-based Classification of Drugs

18.8 KEGG: Drug Groups

18.9 KEGG: Drug Classes

18.10 ChemIDplus

18.11 ChEMBL Target Tree

18.12 UN GHS Classification

18.13 NORMAN Suspect List Exchange Classification

18.14 CCSBase Classification

18.15 EPA DSSTox Classification

18.16 PFAS and Fluorinated Organic Compounds in PubChem

18.17 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DTP/NCI
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    9-bata-D-Arabinofuranosyl-2-fluoroadenine phosphate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.123.703
    9-bata-D-Arabinofuranosyl-2-fluoroadenine phosphate (EC: 616-242-0)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/86795
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  8. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  9. ChEBI
  10. NCI Thesaurus (NCIt)
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  11. Open Targets
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    https://platform-docs.opentargets.org/licence
  12. Toxin and Toxin Target Database (T3DB)
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    http://www.t3db.ca/downloads
  13. ChEMBL
    LICENSE
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    http://www.ebi.ac.uk/Information/termsofuse.html
  14. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  15. DailyMed
  16. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  17. EU Clinical Trials Register
  18. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  19. NCI Investigational Drugs
  20. Japan Chemical Substance Dictionary (Nikkaji)
  21. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  22. National Drug Code (NDC) Directory
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  23. NCI Cancer Drugs
  24. NIPH Clinical Trials Search of Japan
  25. NLM RxNorm Terminology
    LICENSE
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  26. Therapeutic Target Database (TTD)
  27. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  28. Pharos
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    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  29. Springer Nature
  30. Wikidata
  31. PubChem
  32. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
    Antimetabolites, Antineoplastic
    https://www.ncbi.nlm.nih.gov/mesh/68000964
  33. GHS Classification (UNECE)
  34. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  35. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  36. PATENTSCOPE (WIPO)
  37. NCBI
CONTENTS