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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2018-05-20 20:15:54 UTC
HMDB IDHMDB0015206
Secondary Accession Numbers
  • HMDB15206
Metabolite Identification
Common NameFludarabine
DescriptionFludarabine is only found in individuals that have used or taken this drug. Fludarabine (marketed as fludarabine phosphate under the trade name Fludara) is a chemotherapy drug used in the treatment of hematological malignancies. [Wikipedia]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.
Structure
Thumb
Synonyms
ValueSource
2-fluoro-ARA AMPChEBI
2-Fluoroadenine arabinoside 5'-monophosphateChEBI
2F-Ara-AMPChEBI
9-beta-Arabinofuranosyl-2-fluoroadenine-5'-phosphateChEBI
9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphate)ChEBI
9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphateChEBI
FAMPChEBI
FludaraChEBI
Fludarabine 5'-monophosphateChEBI
Fludarabine monophosphateChEBI
2-Fluoroadenine arabinoside 5'-monophosphoric acidGenerator
9-b-Arabinofuranosyl-2-fluoroadenine-5'-phosphateGenerator
9-b-Arabinofuranosyl-2-fluoroadenine-5'-phosphoric acidGenerator
9-beta-Arabinofuranosyl-2-fluoroadenine-5'-phosphoric acidGenerator
9-β-arabinofuranosyl-2-fluoroadenine-5'-phosphateGenerator
9-β-arabinofuranosyl-2-fluoroadenine-5'-phosphoric acidGenerator
9-b-D-Arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphate)Generator
9-b-D-Arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphoric acid)Generator
9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphoric acid)Generator
9-β-D-arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphate)Generator
9-β-D-arabinofuranosyl-2-fluoroadenine 5'-(dihydrogen phosphoric acid)Generator
9-b-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphateGenerator
9-b-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphoric acidGenerator
9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphoric acidGenerator
9-β-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphateGenerator
9-β-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphoric acidGenerator
Fludarabine 5'-monophosphoric acidGenerator
Fludarabine monophosphoric acidGenerator
Fludarabine phosphateHMDB
FaraAMPMeSH
BeneflurMeSH
9 beta-D-Arabinofuranosyl-2-fluoroadenine monophosphateMeSH
F-Ara-AMPMeSH
fluoro-Ara-AMPMeSH
Chemical FormulaC10H13FN5O7P
Average Molecular Weight365.2117
Monoisotopic Molecular Weight365.053662512
IUPAC Name{[(2R,3S,4S,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid
Traditional Namefludarabine
CAS Registry Number75607-67-9
SMILES
NC1=C2N=CN([C@@H]3O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]3O)C2=NC(F)=N1
InChI Identifier
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
InChI KeyGIUYCYHIANZCFB-FJFJXFQQSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as purine ribonucleoside monophosphates. These are nucleotides consisting of a purine base linked to a ribose to which one monophosphate group is attached.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPurine nucleotides
Sub ClassPurine ribonucleotides
Direct ParentPurine ribonucleoside monophosphates
Alternative Parents
Substituents
  • Purine ribonucleoside monophosphate
  • Pentose phosphate
  • Pentose-5-phosphate
  • Glycosyl compound
  • N-glycosyl compound
  • 6-aminopurine
  • Monosaccharide phosphate
  • Pentose monosaccharide
  • Imidazopyrimidine
  • Purine
  • Aminopyrimidine
  • Halopyrimidine
  • 2-halopyrimidine
  • Monoalkyl phosphate
  • Imidolactam
  • Alkyl phosphate
  • Aryl fluoride
  • Aryl halide
  • Monosaccharide
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Pyrimidine
  • Azole
  • Tetrahydrofuran
  • Heteroaromatic compound
  • Imidazole
  • Secondary alcohol
  • 1,2-diol
  • Organoheterocyclic compound
  • Azacycle
  • Oxacycle
  • Organooxygen compound
  • Alcohol
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organohalogen compound
  • Primary amine
  • Amine
  • Organofluoride
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point260 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.97 g/LNot Available
LogP-2.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.97 g/LALOGPS
logP-2.5ALOGPS
logP-3.6ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)1.34ChemAxon
pKa (Strongest Basic)0.6ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area186.07 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity74.93 m³·mol⁻¹ChemAxon
Polarizability28.88 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-9623000000-df7fef014b7ed6f138caView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-01vk-9412300000-a8e2be4c7ab19ccd3280View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0913000000-80f61b17aa4ad7d3fce9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0900000000-e0aa5e8a08f61ff3d3b7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ue9-0900000000-0bba10c09fa50579ea86View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0i29-4409000000-1d1175238eed452b53c2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fb9-8900000000-b0d8f9f14834a2ff1f97View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9200000000-b33283ba6688bd6f3e24View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01073 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01073 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID28532
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFludarabine
METLIN IDNot Available
PubChem Compound30751
PDB IDNot Available
ChEBI ID63599
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [PubMed:11114313 ]
  2. Gonzalez H, Leblond V, Azar N, Sutton L, Gabarre J, Binet JL, Vernant JP, Dighiero G: Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998 Jun;40(3):113-8. [PubMed:9698219 ]
  3. Tournilhac O, Cazin B, Lepretre S, Divine M, Maloum K, Delmer A, Grosbois B, Feugier P, Maloisel F, Villard F, Villemagne B, Bastit D, Belhadj K, Azar N, Michallet M, Manhes G, Travade P: Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood. 2004 Jan 1;103(1):363-5. Epub 2003 Sep 11. [PubMed:12969985 ]

Enzymes

General function:
Involved in ATP binding
Specific function:
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name:
DCK
Uniprot ID:
P27707
Molecular weight:
30518.315
References
  1. Jordheim LP, Galmarini CM, Dumontet C: [Metabolism, mechanism of action and resistance to cytotoxic nucleoside analogues]. Bull Cancer. 2005 Mar;92(3):239-48. [PubMed:15820918 ]
  2. Yao L, Xu W, Fan L, Miao KR, Wu YJ, Qiao C, Zhu DX, Zhu HY, Liu P, Li JY: [Correlation of deoxycytidine kinase gene expression with fludarabine resistance in patients with chronic lymphocytic leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Feb;18(1):36-9. [PubMed:20137114 ]
  3. Zhang Y, Secrist JA 3rd, Ealick SE: The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):133-9. Epub 2006 Jan 18. [PubMed:16421443 ]
General function:
Involved in oxidation reduction
Specific function:
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name:
RRM1
Uniprot ID:
P23921
Molecular weight:
90069.375
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. [PubMed:19519505 ]
  4. Robak T, Korycka A, Lech-Maranda E, Robak P: Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules. 2009 Mar 23;14(3):1183-226. doi: 10.3390/molecules14031183. [PubMed:19325518 ]
General function:
Involved in nucleotide binding
Specific function:
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.
Gene Name:
POLA1
Uniprot ID:
P09884
Molecular weight:
165911.405
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. [PubMed:19519505 ]
  4. Robak T, Korycka A, Lech-Maranda E, Robak P: Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules. 2009 Mar 23;14(3):1183-226. doi: 10.3390/molecules14031183. [PubMed:19325518 ]
  5. Robak T, Lech-Maranda E, Korycka A, Robak E: Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity. Curr Med Chem. 2006;13(26):3165-89. [PubMed:17168705 ]

Transporters

General function:
Involved in nucleoside transmembrane transporter activity
Specific function:
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs)
Gene Name:
SLC29A1
Uniprot ID:
Q99808
Molecular weight:
50218.8
References
  1. Santini D, Vincenzi B, Fratto ME, Perrone G, Lai R, Catalano V, Cass C, Ruffini PA, Spoto C, Muretto P, Rizzo S, Muda AO, Mackey JR, Russo A, Tonini G, Graziano F: Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer. J Cell Physiol. 2010 May;223(2):384-8. doi: 10.1002/jcp.22045. [PubMed:20082300 ]