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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:40:56 UTC
HMDB IDHMDB0015078
Secondary Accession Numbers
  • HMDB15078
Metabolite Identification
Common NameZalcitabine
DescriptionZalcitabine, also known as DDC or hivid, 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. 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. Zalcitabine is a drug which is used for the treatment of human immunovirus (hiv) infections in conjunction with other antivirals. Zalcitabine is an extremely weak basic (essentially neutral) compound (based on its pKa). In humans, zalcitabine is involved in zalcitabine action pathway. Zalcitabine is formally rated as a possible carcinogen (by IARC 2B) and is also a potentially toxic compound. 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. 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. Within cells, zalcitabine is converted to its active metabolite, Zalcitabine 5'-triphosphate (ddCTP), by the sequential action of cellular enzymes. 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.
Structure
Data?1582753256
Synonyms
ValueSource
2',3'-DideoxycytidineChEBI
4-Amino-1-[(2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-oneChEBI
DDCChEBI
DDCYDChEBI
DideoxycytidineChEBI
HividKegg
HIVID rocheHMDB
2',3' DideoxycytidineHMDB
Hoffman-la roche brand OF zalcitabineHMDB
Roche brand OF zalcitabineHMDB
DDC (Antiviral)HMDB
Chemical FormulaC9H13N3O3
Average Molecular Weight211.2178
Monoisotopic Molecular Weight211.095691297
IUPAC Name4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
Traditional Namezalcitabine
CAS Registry Number7481-89-2
SMILES
NC1=NC(=O)N(C=C1)[C@H]1CC[C@@H](CO)O1
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 KeyWREGKURFCTUGRC-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.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleosides
Sub ClassPyrimidine 2',3'-dideoxyribonucleosides
Direct ParentPyrimidine 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 FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point210 - 214 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility7.05 g/LNot Available
LogP-1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.05 g/LALOGPS
logP-1.3ALOGPS
logP-1.2ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)14.67ChemAxon
pKa (Strongest Basic)0.18ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area88.15 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity52.24 m³·mol⁻¹ChemAxon
Polarizability20.86 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-005c-9600000000-2b4de4867a39d5e3055bSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00b9-9800000000-add2e4ce43f76aa31304Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-03di-0190000000-5d3365f648d5f5675ab9Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-066r-2900000000-843d28df71eab94652c3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4l-7900000000-628c9e8f6a131581a8d4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-9200000000-60a00651a71121843a19Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-9000000000-237a0c1094225974a6e8Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-0910000000-95a2a7845a54a61d7c15Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-0900000000-345deba429b644c7b4f5Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-0900000000-6aaba2f2eeb001628ab2Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-03di-5900000000-03b881f85c17ccbe5295Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-01ot-9300000000-2896ce7406bb834c001aSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-03di-0900000000-056961b8bc4067346530Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0900000000-eaacef912c49eac35506Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-4900000000-0712eb98271c7def7fa6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0292-9300000000-b5ae4987aabc3d08e09bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1980000000-983fc19dcf0d0b85cef4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-2900000000-0612e4906539771bd61aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9300000000-b05fd7cbb391f9d8d755Spectrum
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 DB00943 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00943 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 IDDB00943
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID22498
KEGG Compound IDC07207
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkZalcitabine
METLIN IDNot Available
PubChem Compound24066
PDB IDNot Available
ChEBI ID10101
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. [PubMed:7614775 ]
  2. Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. [PubMed:8097417 ]

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. Rossi L, Serafini S, Schiavano GF, Casabianca A, Vallanti G, Chiarantini L, Magnani M: Metabolism, mitochondrial uptake and toxicity of 2', 3'-dideoxycytidine. Biochem J. 1999 Dec 15;344 Pt 3:915-20. [PubMed:10585881 ]
  2. Kitos TE, Tyrrell DL: Intracellular metabolism of 2',3'-dideoxynucleosides in duck hepatocyte primary cultures. Biochem Pharmacol. 1995 May 11;49(9):1291-302. [PubMed:7763311 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name:
CYP3A43
Uniprot ID:
Q9HB55
Molecular weight:
57756.285
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
References
  1. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. [PubMed:10945832 ]
General function:
Involved in transmembrane transport
Specific function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular weight:
60025.0
References
  1. Morita N, Kusuhara H, Sekine T, Endou H, Sugiyama Y: Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1179-84. [PubMed:11504818 ]