T3DB: Cytarabine

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2014-10-14 21:16:36 UTC

Update Date

2014-12-24 20:27:01 UTC

Accession Number

T3D4978

Identification

Common Name

Cytarabine

Class

Small Molecule

Description

A 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

MOL SDF PDB SMILES InChI

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 Formula

C₉H₁₃N₃O₅

Average Molecular Mass

243.217 g/mol

Monoisotopic Mass

243.086 g/mol

CAS Registry Number

147-94-4

IUPAC Name

4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one

Traditional Name

cytarabine

SMILES

[H][C@]1(CO)O[C@@]([H])(N2C=CC(=N)N=C2O)[C@@]([H])(O)[C@]1([H])O

InChI Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Nucleosides, nucleotides, and analogues

Class

Pyrimidine nucleosides

Sub Class

Not Available

Direct Parent

Pyrimidine 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 Framework

Aromatic heteromonocyclic compounds

External Descriptors

monosaccharide derivative (CHEBI:28680 )
beta-D-arabinoside (CHEBI:28680 )
pyrimidine nucleoside (CHEBI:28680 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

Not Available

Experimental Properties

Property	Value
Melting Point	186-188
Boiling Point	Not Available
Solubility	Freely soluble
LogP	-2.8

Predicted Properties

Property	Value	Source
Water Solubility	43.8 g/L	ALOGPS
logP	-2.2	ALOGPS
logP	-2.8	ChemAxon
logS	-0.74	ALOGPS
pKa (Strongest Acidic)	12.55	ChemAxon
pKa (Strongest Basic)	-0.062	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	7	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	128.61 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	54.54 m³·mol⁻¹	ChemAxon
Polarizability	22.53 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-MS (5 TMS)	splash10-0zfr-2951000000-7baf0e1ea8b1a34362e2	JSpectraViewer \| MoNA
GC-MS	GC-MS Spectrum - GC-MS (4 TMS)	splash10-0g4j-2980000000-9337623aef7fec22dd97	JSpectraViewer \| MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0zfr-2951000000-7baf0e1ea8b1a34362e2	JSpectraViewer \| MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0g4j-2980000000-9337623aef7fec22dd97	JSpectraViewer \| MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-08ml-9320000000-b032ad2c3dbed3face55	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-0fuu-3934200000-7c3baaaffddf6aacd0f3	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	JSpectraViewer
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0006-0190000000-eff861edb69ddab2c195	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-0900000000-4b5b14f0a5467db173b6	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-3900000000-d85ae6c771dd9206c4c2	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-06sl-9600000000-b154ca170372bcbf8a4a	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-00lu-9200000000-840df44a2d1149f4a7f7	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-01ox-0790000000-270551529aa609aa9ce8	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-0900000000-855a7f8775ed4351b290	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-0900000000-50671582f88f6b4d8cee	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-1900000000-54269291900f80d353c3	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-7900000000-ae3ff52581cbe6141064	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , positive	splash10-03di-0900000000-9f3ae8e87da22e4e2e82	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0btc-3910000000-0c7172b1308a7ac699d4	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-03di-0900000000-204e273853aa2d8e09ab	JSpectraViewer \| MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0910000000-9575881412c4c94a7eae	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-5900000000-2cb5f7e3dbd7baa35b56	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03dj-9600000000-7d281b2b2d57c8786e11	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01ox-0960000000-db9207082a1fabf42dae	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03xs-4910000000-c89de30dd376cbcb3b66	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00kf-9200000000-5715839499753b91f845	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0900000000-61fe3ac4032a2baf1b89	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-2900000000-230b224d4d0dd71d0a49	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-02t9-9200000000-7262e80c4fe078b890fc	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-2900000000-66dec45988a096cc3483	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ox-9500000000-bc463e76fd8ac42ac1d0	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9100000000-98e1626c7f485521a57f	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
2D NMR	[1H,1H] 2D NMR Spectrum	Not Available	JSpectraViewer
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	JSpectraViewer

Toxicity Profile

Route of Exposure

Less than 20% of the orally administered dose is absorbed from the gastrointestinal tract.

Mechanism of Toxicity

Cytarabine 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.

Metabolism

Hepatic.

Toxicity Values

Cytarabine syndrome may develop - it is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For the treatment of acute non-lymphocytic leukemia, acute lymphocytic leukemia and blast phase of chronic myelocytic leukemia.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

28680

BioCyc ID

Not Available

CTD ID

D003561

Stitch ID

Not Available

PDB ID

AR3

ACToR ID

Not Available

Wikipedia Link

Cytarabine

References

Synthesis Reference

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

MSDS

T3D4978.pdf

General References

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 ]
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 ]
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 ]
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 ]
Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. DNA polymerase beta

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

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 ]
Miura S, Izuta S: DNA polymerases as targets of anticancer nucleosides. Curr Drug Targets. 2004 Feb;5(2):191-5. [15011952 ]
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

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 ]
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 ]

Target Details

3. Deoxycytidine kinase

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

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 ]

Cytarabine (T3D4978)

Structure for T3D4978: Cytarabine

Targets

References

References

References