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Record Information
Version2.0
Creation Date2014-10-14 21:16:36 UTC
Update Date2014-12-24 20:27:01 UTC
Accession NumberT3D4978
Identification
Common NameCytarabine
ClassSmall Molecule
DescriptionA pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
Compound Type
  • Antimetabolite, Antineoplastic
  • Antiviral Agent
  • Drug
  • Immunosuppressive Agent
  • Metabolite
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(beta-D-arabinofuranosyl)cytosine
1-Arabinofuranosylcytosine
1-beta -D-Arabinofaranosylcytosine
1-beta -D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-beta -D-Arabinofuranosylcytosine
1-beta-D-Arabinofaranosylcytosine
1-beta-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-beta-D-Arabinofuranosyl-Cytosine
1-beta-D-Arabinofuranosylcytosine
1-beta-D-Arabinofuranosylcytosine, Cytosine Arabinoside
1-beta-D-Arabinosyl-Cytosine
1-beta-D-Arabinosylcytosine
1beta -Arabinofuranasylcytosine
1beta -D-Arabinofuranosylcytosine
1beta -D-Arabinosylcytosine
1beta-Arabinofuranasylcytosine
1beta-D-Arabinofuranosylcytosine
1beta-D-Arabinosylcytosine
2(1H)-Pyrimidinone, 4-amino-1- -D-arabinofuranosyl
4-Amino-1-arabinofuranosyl-2-oxo-1,2-dihydropyrimidin
4-Amino-1-arabinofuranosyl-2-oxo-1,2-dihydropyrimidine
4-Amino-1-b-D-arabinofuranosyl-2-(1H)-pyrimidinone
4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinone
4-amino-1-beta-D-arabinofuranosylpyrimidin-2(1H)-one
Alexan
Ara-C
Arabinocytidine
Arabinofuranosyl Cytidine
Arabinofuranosylcytosine
Arabinosylcytosine
Arabitin
AraC
Aracytidine
Aracytin
Aracytine
Arafcyt
beta -arabinosylcytosine
beta -cytosine arabinoside
beta -D-arabinosylcytosine
beta-Ara c
beta-Arabinosylcytosine
beta-Cytosine arabinoside
beta-D-Arabinosylcytosine
Citarabina
Cytarabin
Cytarabina
Cytarabine liposome injection
Cytarabinoside
Cytarabinum
Cytonal
Cytosar
Cytosar-U
Cytosine 1-beta-D-arabinofuranoside
Cytosine arabinofuranoside
Cytosine arabinose
Cytosine arabinoside
Cytosine beta-D-arabinofuranoside
Cytosine beta-D-arabinoside
Cytosine, beta -D-arabinoside
Cytosine, beta-D-arabinoside
Cytosine-1-beta-D-arabinofuranoside
Cytosine-1-beta-D-arabinofuranoside hydrochloride
Cytosine-beta -arabinoside
Cytosine-beta -D-arabinofuranoside
Cytosine-beta-arabinoside
Cytosine-beta-D-arabinofuranoside
cytosine-β-D-arabinofuranoside
Cytosinearabinoside
Depocyt
Depocyte
Erpalfa
Iretin
Spongocytidine
Tarabine
Udicil
Chemical FormulaC9H13N3O5
Average Molecular Mass243.217 g/mol
Monoisotopic Mass243.086 g/mol
CAS Registry Number147-94-4
IUPAC Name4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
Traditional Namecytarabine
SMILES[H][C@]1(CO)O[C@@]([H])(N2C=CC(=N)N=C2O)[C@@]([H])(O)[C@]1([H])O
InChI IdentifierInChI=1S/C9H13N3O5/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16)/t4-,6-,7+,8-/m1/s1
InChI KeyInChIKey=UHDGCWIWMRVCDJ-CCXZUQQUSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrimidine nucleosides. Pyrimidine nucleosides are compounds comprising a pyrimidine base attached to a ribosyl or deoxyribosyl moiety.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleosides
Sub ClassNot Available
Direct ParentPyrimidine nucleosides
Alternative Parents
Substituents
  • Pyrimidine nucleoside
  • Glycosyl compound
  • N-glycosyl compound
  • Pentose monosaccharide
  • Aminopyrimidine
  • Pyrimidone
  • Hydropyrimidine
  • Monosaccharide
  • Pyrimidine
  • Imidolactam
  • Tetrahydrofuran
  • Heteroaromatic compound
  • Secondary alcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Primary alcohol
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary amine
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point186-188
Boiling PointNot Available
SolubilityFreely soluble
LogP-2.8
Predicted Properties
PropertyValueSource
Water Solubility43.8 g/LALOGPS
logP-2.2ALOGPS
logP-2.8ChemAxon
logS-0.74ALOGPS
pKa (Strongest Acidic)12.55ChemAxon
pKa (Strongest Basic)-0.062ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area128.61 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity54.54 m³·mol⁻¹ChemAxon
Polarizability22.53 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-MS (5 TMS)splash10-0zfr-2951000000-7baf0e1ea8b1a34362e2JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (4 TMS)splash10-0g4j-2980000000-9337623aef7fec22dd97JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0zfr-2951000000-7baf0e1ea8b1a34362e2JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0g4j-2980000000-9337623aef7fec22dd97JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-08ml-9320000000-b032ad2c3dbed3face55JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0fuu-3934200000-7c3baaaffddf6aacd0f3JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-0190000000-eff861edb69ddab2c195JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-0900000000-4b5b14f0a5467db173b6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-3900000000-d85ae6c771dd9206c4c2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-06sl-9600000000-b154ca170372bcbf8a4aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00lu-9200000000-840df44a2d1149f4a7f7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-01ox-0790000000-270551529aa609aa9ce8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-0900000000-855a7f8775ed4351b290JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-0900000000-50671582f88f6b4d8ceeJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-1900000000-54269291900f80d353c3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-7900000000-ae3ff52581cbe6141064JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-03di-0900000000-9f3ae8e87da22e4e2e82JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0910000000-9575881412c4c94a7eaeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-5900000000-2cb5f7e3dbd7baa35b56JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03dj-9600000000-7d281b2b2d57c8786e11JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01ox-0960000000-db9207082a1fabf42daeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03xs-4910000000-c89de30dd376cbcb3b66JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-9200000000-5715839499753b91f845JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,1H] 2D NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureLess than 20% of the orally administered dose is absorbed from the gastrointestinal tract.
Mechanism of ToxicityCytarabine acts through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking the progression of cells from the G1 phase to the S-phase. Although the mechanism of action is not completely understood, it appears that cytarabine acts through the inhibition of DNA polymerase. A limited, but significant, incorporation of cytarabine into both DNA and RNA has also been reported.
MetabolismHepatic.
Toxicity ValuesCytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of acute non-lymphocytic leukemia, acute lymphocytic leukemia and blast phase of chronic myelocytic leukemia.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00987
HMDB IDHMDB15122
PubChem Compound ID6253
ChEMBL IDCHEMBL803
ChemSpider ID6017
KEGG IDC02961
UniProt IDNot Available
OMIM ID
ChEBI ID28680
BioCyc IDNot Available
CTD IDD003561
Stitch IDNot Available
PDB IDAR3
ACToR IDNot Available
Wikipedia LinkCytarabine
References
Synthesis Reference

Michael Kluge, Herbert Schott, “Cytarabine derivatives, the preparation and use thereof.” U.S. Patent US5641758, issued August, 1992.

MSDST3D4978.pdf
General References
  1. Zaky DA, Betts RF, Douglas RG Jr, Bengali K, Neil GL: Varicella-zoster virus and subcutaneous cytarabine: correlation of in vitro sensitivities to blood levels. Antimicrob Agents Chemother. 1975 Mar;7(3):229-32. [166610 ]
  2. Relling MV, Mulhern RK, Fairclough D, Baker D, Pui CH: Chlorpromazine with and without lorazepam as antiemetic therapy in children receiving uniform chemotherapy. J Pediatr. 1993 Nov;123(5):811-6. [8229497 ]
  3. Mallick KS, Hajek AS, Parrish RK 2nd: Fluorouracil (5-FU) and cytarabine (ara-C) inhibition of corneal epithelial cell and conjunctival fibroblast proliferation. Arch Ophthalmol. 1985 Sep;103(9):1398-402. [4038134 ]
  4. Bursztyn J, Boccara JF, Paillassou B, Bavoux F: [Corneal toxicity of cytarabine. Apropos of a case]. Ophtalmologie. 1989 Jun-Aug;3(3):229-30. [2641118 ]
  5. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Microtubule binding
Specific Function:
Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.
Gene Name:
POLB
Uniprot ID:
P06746
Molecular Weight:
38177.34 Da
References
  1. Angeli JP, Ribeiro LR, Bellini MF, Mantovanil: Anti-clastogenic effect of beta-glucan extracted from barley towards chemically induced DNA damage in rodent cells. Hum Exp Toxicol. 2006 Jun;25(6):319-24. [16866189 ]
  2. Miura S, Izuta S: DNA polymerases as targets of anticancer nucleosides. Curr Drug Targets. 2004 Feb;5(2):191-5. [15011952 ]
  3. Krynetskaia NF, Phadke MS, Jadhav SH, Krynetskiy EY: Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72. doi: 10.1158/1535-7163.MCT-08-0695. [19372559 ]
2. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Prakasha Gowda AS, Polizzi JM, Eckert KA, Spratt TE: Incorporation of gemcitabine and cytarabine into DNA by DNA polymerase beta and ligase III/XRCC1. Biochemistry. 2010 Jun 15;49(23):4833-40. doi: 10.1021/bi100200c. [20459144 ]
  2. Foti M, Omichinski JG, Stahl S, Maloney D, West J, Schweitzer BI: Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor. FEBS Lett. 1999 Feb 5;444(1):47-53. [10037146 ]
General Function:
Protein homodimerization activity
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 Da
References
  1. Mancini WR: The role of deoxycytidine-metabolizing enzymes in the cytotoxicity induced by 3'-amino-2',3'-dideoxycytidine and cytosine arabinoside. Cancer Chemother Pharmacol. 1992;30(2):139-44. [1318170 ]