T3DB: Zalcitabine

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation XML

Record Information

Version

2.0

Creation Date

2014-09-11 02:06:20 UTC

Update Date

2014-12-24 20:26:56 UTC

Accession Number

T3D4719

Identification

Common Name

Zalcitabine

Class

Small Molecule

Description

A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of 5' to 3' phosphodiester linkages, which are needed for the elongation of DNA chains, thus resulting in the termination of viral DNA growth. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.

Compound Type

Amine
Anti-HIV Agent
Antimetabolite
Drug
Ether
Metabolite
Organic Compound
Reverse Transcriptase Inhibitor
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2',3'-Dideoxycytidine
4-amino-1-[(2R,5S)-5-(Hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one
DDC
DDCYD
Dideoxycytidine
HIVID

Chemical Formula

C₉H₁₃N₃O₃

Average Molecular Mass

211.218 g/mol

Monoisotopic Mass

211.096 g/mol

CAS Registry Number

7481-89-2

IUPAC Name

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

Traditional Name

zalcitabine

SMILES

[H][C@@]1(CO)CC[C@@]([H])(O1)N1C=CC(=N)N=C1O

InChI Identifier

InChI=1S/C9H13N3O3/c10-7-3-4-12(9(14)11-7)8-2-1-6(5-13)15-8/h3-4,6,8,13H,1-2,5H2,(H2,10,11,14)/t6-,8+/m0/s1

InChI Key

InChIKey=WREGKURFCTUGRC-POYBYMJQSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as pyrimidine 2',3'-dideoxyribonucleosides. Pyrimidine 2',3'-dideoxyribonucleosides are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at positions 2 and 3.

Kingdom

Organic compounds

Super Class

Nucleosides, nucleotides, and analogues

Class

Pyrimidine nucleosides

Sub Class

Pyrimidine 2',3'-dideoxyribonucleosides

Direct Parent

Pyrimidine 2',3'-dideoxyribonucleosides

Alternative Parents

Substituents

Pyrimidine 2',3'-dideoxyribonucleoside
Aminopyrimidine
Pyrimidone
Hydropyrimidine
Pyrimidine
Imidolactam
Heteroaromatic compound
Tetrahydrofuran
Oxacycle
Azacycle
Organoheterocyclic compound
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Primary amine
Primary alcohol
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Alcohol
Amine
Organic nitrogen compound
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

pyrimidine 2',3'-dideoxyribonucleoside (CHEBI:10101 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
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

White powder.

Experimental Properties

Property	Value
Melting Point	217 - 218°C
Boiling Point	Not Available
Solubility	7.05e+00 g/L
LogP	-1.3

Predicted Properties

Property	Value	Source
Water Solubility	7.05 g/L	ALOGPS
logP	-1.3	ALOGPS
logP	-1.2	ChemAxon
logS	-1.5	ALOGPS
pKa (Strongest Acidic)	14.67	ChemAxon
pKa (Strongest Basic)	0.18	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	88.15 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	52.24 m³·mol⁻¹	ChemAxon
Polarizability	20.86 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
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-005c-9600000000-2b4de4867a39d5e3055b	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00b9-9800000000-add2e4ce43f76aa31304	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	splash10-03di-0190000000-5d3365f648d5f5675ab9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-066r-2900000000-843d28df71eab94652c3	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4l-7900000000-628c9e8f6a131581a8d4	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0006-9200000000-60a00651a71121843a19	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0006-9000000000-237a0c1094225974a6e8	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-0910000000-95a2a7845a54a61d7c15	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-0900000000-345deba429b644c7b4f5	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-0900000000-6aaba2f2eeb001628ab2	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-03di-5900000000-03b881f85c17ccbe5295	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-01ot-9300000000-2896ce7406bb834c001a	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , positive	splash10-03di-0900000000-056961b8bc4067346530	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-03di-1900000000-1054737ea962191f8ea3	JSpectraViewer \| MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-1980000000-983fc19dcf0d0b85cef4	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-014i-2900000000-0612e4906539771bd61a	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9300000000-b05fd7cbb391f9d8d755	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0490000000-57082a1867cdc2c9822a	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ox-9600000000-f474e998724df983de8c	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9300000000-20ef263f8c644fd3e58e	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0900000000-eaacef912c49eac35506	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-4900000000-0712eb98271c7def7fa6	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0292-9300000000-b5ae4987aabc3d08e09b	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0900000000-fa8c6be751e9c08c099b	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-3900000000-acfad49c533143abebc1	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-014i-9100000000-9b080034478e10638d8e	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

Toxicity Profile

Route of Exposure

Bioavailability is over 80% following oral administration.

Mechanism of Toxicity

Zalcitabine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Within cells, zalcitabine is converted to its active metabolite, dideoxycytidine 5'-triphosphate (ddCTP), by the sequential action of cellular enzymes. ddCTP interferes with viral RNA-directed DNA polymerase (reverse transcriptase) by competing for utilization of the natural substrate deoxycytidine 5'-triphosphate (dCTP), as well as incorpating into viral DNA. Due to it's lack of a 3'-OH group, the formation of a 5' to 3' phosphodiester linkage that is necessary for DNA chain elongation is inhibited, thus leading to the termination of viral DNA growth.

Metabolism

Hepatic. Route of Elimination: Renal excretion of unchanged drug appears to be the primary route of elimination, accounting for approximately 80% of an intravenous dose and 60% of an orally administered dose within 24 hours after dosing (n=19). Renal clearance exceeds glomerular filtration rate suggesting renal tubular secretion contributes to the elimination of zalcitabine by the kidneys. Half Life: 2 hours

Toxicity Values

Acute overdose: Inadvertent pediatric overdoses have occurred with doses up to 1.5 mg/kg zalcitabine. Chronic overdose: in an initial dose-finding study in which zalcitabine was administered at doses 25 times (0.25 mg/kg every 8 hours) the currently recommended dose, one patient discontinued zalcitabine after 1.5 weeks of treatment subsequent to the development of a rash and fever.

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2B, possibly carcinogenic to humans. (4)

Uses/Sources

For the treatment of Human immunovirus (HIV) infections in conjunction with other antivirals.

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

10101

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Zalcitabine

References

Synthesis Reference

Not Available

MSDS

Link

General References

Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. [8097417 ]
Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. [7614775 ]
Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. [Link]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Zalcitabine (T3D4719)

Structure for T3D4719: Zalcitabine