Identification

Name
Zalcitabine
Accession Number
DB00943  (APRD00562)
Type
Small Molecule
Groups
Approved, Investigational
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A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen.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. [PubChem]

Structure
Thumb
Synonyms
  • 2',3'-Dideoxycytidine
  • 4-amino-1-[(2R,5S)-5-(Hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one
  • DDC
  • DDCYD
  • Dideoxycytidine
External IDs
RO 24-2027/000
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hivid Tab 0.375mgTablet.375 mgOralHoffmann La Roche1992-12-312003-07-30Canada
Hivid Tab 0.75 mgTablet.75 mgOralHoffmann La Roche1992-12-312006-07-25Canada
International/Other Brands
HIVID
Categories
UNII
6L3XT8CB3I
CAS number
7481-89-2
Weight
Average: 211.2178
Monoisotopic: 211.095691297
Chemical Formula
C9H13N3O3
InChI Key
WREGKURFCTUGRC-POYBYMJQSA-N
InChI
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
IUPAC Name
4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1)[[email protected]]1CC[[email protected]@H](CO)O1

Pharmacology

Indication

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

Structured Indications
Not Available
Pharmacodynamics

Zalcitabine is an analog of 2'-deoxycytidine that is pharmacologically related to but structurally different from other nucleotide reverse transcriptase inhibitors (NRTIs). Zalcitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

Mechanism of action

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.

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
Absorption

Bioavailability is over 80% following oral administration.

Volume of distribution
  • 0.304 to 0.734 L/kg
Protein binding

Less than 4%

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

Clearance
  • 285 mL/min [HIV-infected patients receiving 1.5 mg IV infusion for 1 hour]
Toxicity

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 1½ weeks of treatment subsequent to the development of a rash and fever.

Affected organisms
  • Human Immunodeficiency Virus
Pathways
PathwayCategory
Zalcitabine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Zalcitabine can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe metabolism of Zalcitabine can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Zalcitabine can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Zalcitabine can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Zalcitabine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Zalcitabine can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Zalcitabine can be decreased when combined with Betaxolol.Approved
BoceprevirThe metabolism of Zalcitabine can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Zalcitabine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Zalcitabine can be decreased when it is combined with Bosentan.Approved, Investigational
BupropionThe metabolism of Zalcitabine can be decreased when combined with Bupropion.Approved
CapecitabineThe metabolism of Zalcitabine can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Zalcitabine can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Zalcitabine can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Zalcitabine can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Zalcitabine can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Zalcitabine can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Zalcitabine can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Zalcitabine can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Zalcitabine can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Zalcitabine can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Zalcitabine can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Zalcitabine can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Zalcitabine can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Zalcitabine can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Zalcitabine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Zalcitabine can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Zalcitabine can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Zalcitabine can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Zalcitabine can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Zalcitabine can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Zalcitabine can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Zalcitabine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Zalcitabine can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Zalcitabine can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Zalcitabine can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Zalcitabine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Zalcitabine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Zalcitabine can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Zalcitabine can be decreased when combined with Desipramine.Approved
DihydroergotamineThe metabolism of Zalcitabine can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Zalcitabine can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Zalcitabine can be decreased when combined with Diphenhydramine.Approved
DosulepinThe metabolism of Zalcitabine can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Zalcitabine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Zalcitabine can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Zalcitabine can be decreased when combined with Duloxetine.Approved
EfavirenzThe metabolism of Zalcitabine can be decreased when combined with Efavirenz.Approved, Investigational
EliglustatThe metabolism of Zalcitabine can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Zalcitabine can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Zalcitabine can be decreased when combined with Erythromycin.Approved, Vet Approved
EtravirineThe metabolism of Zalcitabine can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Zalcitabine can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Zalcitabine can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Zalcitabine can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Zalcitabine can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe metabolism of Zalcitabine can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Zalcitabine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Zalcitabine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Zalcitabine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Zalcitabine can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Zalcitabine can be increased when it is combined with Fusidic Acid.Approved
GanciclovirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Zalcitabine.Approved, Investigational
GemfibrozilThe metabolism of Zalcitabine can be decreased when combined with Gemfibrozil.Approved
HaloperidolThe metabolism of Zalcitabine can be decreased when combined with Haloperidol.Approved
IdelalisibThe serum concentration of Zalcitabine can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Zalcitabine can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Zalcitabine can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Zalcitabine can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Zalcitabine can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Zalcitabine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Zalcitabine can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Zalcitabine can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Zalcitabine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Zalcitabine can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Zalcitabine can be decreased when combined with Ketoconazole.Approved, Investigational
LeflunomideThe metabolism of Zalcitabine can be decreased when combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Zalcitabine can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Zalcitabine can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Zalcitabine can be decreased when combined with Lorcaserin.Approved
LosartanThe metabolism of Zalcitabine can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Zalcitabine can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Zalcitabine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Zalcitabine can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Zalcitabine can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Zalcitabine can be decreased when combined with Manidipine.Approved, Investigational
MethadoneThe metabolism of Zalcitabine can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Zalcitabine can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Zalcitabine can be decreased when combined with Metoprolol.Approved, Investigational
MidostaurinThe metabolism of Zalcitabine can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Zalcitabine can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Zalcitabine can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Zalcitabine can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Zalcitabine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Zalcitabine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Zalcitabine can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Zalcitabine can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Zalcitabine can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Zalcitabine can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Zalcitabine can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Zalcitabine can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Zalcitabine can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Zalcitabine can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Zalcitabine can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Zalcitabine can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Zalcitabine can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Zalcitabine can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Zalcitabine can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Zalcitabine can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Zalcitabine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Zalcitabine can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Zalcitabine can be decreased when combined with Promazine.Approved, Vet Approved
PyrimethamineThe metabolism of Zalcitabine can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinidineThe metabolism of Zalcitabine can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Zalcitabine can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Zalcitabine can be decreased when combined with Ranolazine.Approved, Investigational
RibavirinRibavirin may increase the hepatotoxic activities of Zalcitabine.Approved
RifabutinThe metabolism of Zalcitabine can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Zalcitabine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Zalcitabine can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Zalcitabine can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Zalcitabine can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Zalcitabine can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Zalcitabine can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Zalcitabine can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Zalcitabine can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Zalcitabine can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Zalcitabine can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Zalcitabine can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Zalcitabine can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Zalcitabine can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Zalcitabine can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Zalcitabine can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Zalcitabine can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Zalcitabine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Zalcitabine can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Zalcitabine can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Zalcitabine can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TeriflunomideThe serum concentration of Zalcitabine can be increased when it is combined with Teriflunomide.Approved
ThioridazineThe metabolism of Zalcitabine can be decreased when combined with Thioridazine.Approved, Withdrawn
TicagrelorThe metabolism of Zalcitabine can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Zalcitabine can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Zalcitabine can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Zalcitabine can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Zalcitabine can be decreased when combined with Tolbutamide.Approved
TopiroxostatThe metabolism of Zalcitabine can be decreased when combined with Topiroxostat.Approved, Investigational
TranylcypromineThe metabolism of Zalcitabine can be decreased when combined with Tranylcypromine.Approved
TrimethoprimThe metabolism of Zalcitabine can be decreased when combined with Trimethoprim.Approved, Vet Approved
ValganciclovirThe risk or severity of adverse effects can be increased when Valganciclovir is combined with Zalcitabine.Approved, Investigational
Valproic AcidThe metabolism of Zalcitabine can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Zalcitabine can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Zalcitabine can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Zalcitabine can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Zalcitabine can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Zalcitabine can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Zalcitabine can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Do not take calcium, aluminium, magnesium or iron supplements within 2 hours of taking this medication.
  • Take on empty stomach: 1 hour before or 2 hours after meals.

References

General References
  1. Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. [PubMed:8097417]
  2. Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. [PubMed:7614775]
External Links
Human Metabolome Database
HMDB15078
KEGG Drug
D00412
KEGG Compound
C07207
PubChem Compound
24066
PubChem Substance
46507879
ChemSpider
22498
BindingDB
50145605
ChEBI
10101
ChEMBL
CHEMBL853
Therapeutic Targets Database
DNC000527
PharmGKB
PA451950
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Zalcitabine
ATC Codes
J05AF03 — Zalcitabine
FDA label
Download (244 KB)
MSDS
Download (36 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections15
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Progressive Multifocal Leukoencephalopathy1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections7
4CompletedTreatmentHemophilia A / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections9

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
Packagers
Dosage forms
FormRouteStrength
TabletOral.375 mg
TabletOral.75 mg
Prices
Unit descriptionCostUnit
Hivid 0.75 mg tablet2.84USD tablet
Hivid 0.375 mg tablet2.27USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)217-218 °CPhysProp
water solubility7.64E+004 mg/L (at 25 °C)PHYSICIANS DESK REFERENCE (2001)
logP-1.30SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility7.05 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity52.24 m3·mol-1ChemAxon
Polarizability20.86 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9972
Blood Brain Barrier+0.9761
Caco-2 permeable-0.7931
P-glycoprotein substrateNon-substrate0.7746
P-glycoprotein inhibitor INon-inhibitor0.937
P-glycoprotein inhibitor IINon-inhibitor0.9171
Renal organic cation transporterNon-inhibitor0.8163
CYP450 2C9 substrateNon-substrate0.8286
CYP450 2D6 substrateNon-substrate0.8493
CYP450 3A4 substrateNon-substrate0.5762
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8893
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9213
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.8626
BiodegradationNot ready biodegradable0.8721
Rat acute toxicity2.0606 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.925
hERG inhibition (predictor II)Non-inhibitor0.875
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0190000000-5d3365f648d5f5675ab9
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-066r-2900000000-843d28df71eab94652c3
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0a4l-7900000000-628c9e8f6a131581a8d4
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0006-9200000000-60a00651a71121843a19
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0006-9000000000-237a0c1094225974a6e8
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-0910000000-95a2a7845a54a61d7c15
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-0900000000-345deba429b644c7b4f5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-0900000000-6aaba2f2eeb001628ab2
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-5900000000-03b881f85c17ccbe5295
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01ot-9300000000-2896ce7406bb834c001a
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-03di-0900000000-056961b8bc4067346530

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrimidine 2',3'-dideoxyribonucleosides. These 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
Pyrimidones / Aminopyrimidines and derivatives / Imidolactams / Hydropyrimidines / Tetrahydrofurans / Heteroaromatic compounds / Oxacyclic compounds / Azacyclic compounds / Primary amines / Primary alcohols
show 3 more
Substituents
Pyrimidine 2',3'-dideoxyribonucleoside / Aminopyrimidine / Pyrimidone / Hydropyrimidine / Pyrimidine / Imidolactam / Heteroaromatic compound / Tetrahydrofuran / Oxacycle / Azacycle
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidine 2',3'-dideoxyribonucleoside (CHEBI:10101)

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72547
Uniprot Name
Reverse transcriptase/RNaseH
Molecular Weight
65223.615 Da
References
  1. Devineni D, Gallo JM: Zalcitabine. Clinical pharmacokinetics and efficacy. Clin Pharmacokinet. 1995 May;28(5):351-60. [PubMed:7614775]
  2. Adkins JC, Peters DH, Faulds D: Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection. Drugs. 1997 Jun;53(6):1054-80. [PubMed:9179531]

Enzymes

Details
1. Deoxycytidine kinase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
Molecular Weight
30518.315 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Monooxygenase activity
Specific Function
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name
CYP3A43
Uniprot ID
Q9HB55
Uniprot Name
Cytochrome P450 3A43
Molecular Weight
57669.21 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
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]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bocedi A, Notaril S, Narciso P, Bolli A, Fasano M, Ascenzi P: Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. [PubMed:15814459]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion 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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD: Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol. 2001 Apr-Jun;18(2):161-7. [PubMed:11463208]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
Gene Name
SLC29A2
Uniprot ID
Q14542
Uniprot Name
Equilibrative nucleoside transporter 2
Molecular Weight
50112.335 Da
References
  1. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD: Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol. 2001 Apr-Jun;18(2):161-7. [PubMed:11463208]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:44