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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2020-02-26 21:40:18 UTC
HMDB IDHMDB0014769
Secondary Accession Numbers
  • HMDB14769
Metabolite Identification
Common NameClofarabine
DescriptionClofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out.
Structure
Data?1582753218
Synonyms
ValueSource
(2R,3R,4S,5R)-5-(6-Amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-olChEBI
2-Chloro-9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenineChEBI
2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenineChEBI
CAFdAChEBI
CL-F-Ara-aChEBI
ClofarabinaChEBI
ClofarabinumChEBI
ClolarKegg
2-Chloro-9-(2'-deoxy-2'-fluoro-b-D-arabinofuranosyl)adenineGenerator
2-Chloro-9-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)adenineGenerator
2-Chloro-9-(2-deoxy-2-fluoro-b-D-arabinofuranosyl)adenineGenerator
2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenineGenerator
2-Chloro-2'-fluoroarabino-2'-deoxyadenosineHMDB
2-Chloro-2'-arabino-fluoro-2'-deoxyadenosineHMDB
2-Chloro-9-(2-deoxy-2-fluoroarabinofuranosyl)adenineHMDB
2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arbinofuranosyl)adenineHMDB
ClofarexHMDB
EvoltraHMDB
2 Chloro 2' arabino fluoro 2' deoxyadenosineMeSH
2 Chloro 2' fluoroarabino 2' deoxyadenosineMeSH
Chemical FormulaC10H11ClFN5O3
Average Molecular Weight303.677
Monoisotopic Molecular Weight303.053445155
IUPAC Name(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
Traditional Nameclofarabine
CAS Registry Number123318-82-1
SMILES
[H][C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C=NC2=C(N)N=C(Cl)N=C12
InChI Identifier
InChI=1S/C10H11ClFN5O3/c11-10-15-7(13)5-8(16-10)17(2-14-5)9-4(12)6(19)3(1-18)20-9/h2-4,6,9,18-19H,1H2,(H2,13,15,16)/t3-,4+,6-,9-/m1/s1
InChI KeyWDDPHFBMKLOVOX-AYQXTPAHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as purine 2'-deoxyribonucleosides. Purine 2'-deoxyribonucleosides are compounds consisting of a purine linked to a ribose which lacks a hydroxyl group at position 2.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPurine nucleosides
Sub ClassPurine 2'-deoxyribonucleosides
Direct ParentPurine 2'-deoxyribonucleosides
Alternative Parents
Substituents
  • Purine 2'-deoxyribonucleoside
  • 6-aminopurine
  • Imidazopyrimidine
  • Purine
  • Aminopyrimidine
  • 2-halopyrimidine
  • Halopyrimidine
  • Aryl chloride
  • Aryl halide
  • N-substituted imidazole
  • Imidolactam
  • Pyrimidine
  • Azole
  • Heteroaromatic compound
  • Imidazole
  • Tetrahydrofuran
  • Secondary alcohol
  • Fluorohydrin
  • Halohydrin
  • Organoheterocyclic compound
  • Oxacycle
  • Azacycle
  • Primary alcohol
  • Organohalogen compound
  • Organochloride
  • Alkyl fluoride
  • Alcohol
  • Organofluoride
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Primary amine
  • Organooxygen compound
  • Alkyl halide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility4.89 g/LNot Available
LogP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.89 g/LALOGPS
logP0.32ALOGPS
logP-0.29ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area119.31 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67 m³·mol⁻¹ChemAxon
Polarizability26.06 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9120000000-e007ae055e3973489f73Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-014i-5932000000-049fdb03acd50f8641cdSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-1903000000-294bd193e470f829e963Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-1903000000-294bd193e470f829e963Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-f17f83cd8dba3d2082b9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0900000000-34b5bafd796f8fec0b13Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ac0-0900000000-640ac0c897663dd584dbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udu-0294000000-9ccca97e93ca09d3e79dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02ai-0930000000-1ebe1a63cd5892cdfd92Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00lr-4900000000-3c46b8a6d7f8a4613053Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00631 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00631 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00631
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID106472
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkClofarabine
METLIN IDNot Available
PubChem Compound119182
PDB IDNot Available
ChEBI ID681569
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]
  2. Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. doi: 10.1517/14656560902997990. [PubMed:19463072 ]
  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. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
  5. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]

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. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  2. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
  3. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710 ]
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. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  4. Authors unspecified: Clofarabine. Drugs R D. 2004;5(4):213-7. [PubMed:15230627 ]
  5. Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. [PubMed:18780321 ]
  6. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]
  7. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710 ]
  8. 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 ]
  9. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]
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. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817 ]
  4. Authors unspecified: Clofarabine. Drugs R D. 2004;5(4):213-7. [PubMed:15230627 ]
  5. Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. [PubMed:18780321 ]
  6. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851 ]
  7. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710 ]
  8. 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 ]
  9. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular weight:
72313.5
References
  1. de Wolf C, Jansen R, Yamaguchi H, de Haas M, van de Wetering K, Wijnholds J, Beijnen J, Borst P: Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther. 2008 Sep;7(9):3092-102. doi: 10.1158/1535-7163.MCT-08-0427. Epub 2008 Sep 2. [PubMed:18765824 ]