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Record Information
Version2.0
Creation Date2014-09-11 02:06:22 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4720
Identification
Common NameZidovudine
ClassSmall Molecule
DescriptionA dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
Compound Type
  • Amide
  • Anti-HIV Agent
  • Antimetabolite
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Reverse Transcriptase Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Azidothymidine
AZT
Retrovir
ZDV
Zidovudin
Zidovudinum
Chemical FormulaC10H13N5O4
Average Molecular Mass267.241 g/mol
Monoisotopic Mass267.097 g/mol
CAS Registry Number30516-87-1
IUPAC Name1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
Traditional Namezidovudine
SMILES[H][C@]1(CO)O[C@]([H])(C[C@]1([H])N=[N+]=[N-])N1C=C(C)C(O)=NC1=O
InChI IdentifierInChI=1S/C10H13N5O4/c1-5-3-15(10(18)12-9(5)17)8-2-6(13-14-11)7(4-16)19-8/h3,6-8,16H,2,4H2,1H3,(H,12,17,18)/t6-,7+,8+/m0/s1
InChI KeyInChIKey=HBOMLICNUCNMMY-XLPZGREQSA-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
  • Pyrimidone
  • Hydroxypyrimidine
  • Hydropyrimidine
  • Pyrimidine
  • Tetrahydrofuran
  • Heteroaromatic compound
  • Azo imide
  • Azo compound
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic zwitterion
  • Alcohol
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point113 - 115°C
Boiling PointNot Available
Solubility2.01E+004 mg/L (at 25°C)
LogP0.05
Predicted Properties
PropertyValueSource
Water Solubility16.3 g/LALOGPS
logP-0.1ALOGPS
logP-0.3ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area108.3 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity61.7 m³·mol⁻¹ChemAxon
Polarizability24.77 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-9220000000-d55aacb79cb345dd1f0aJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0100-9631000000-1d566216a7cf9f0cc760JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0190000000-46ee7eb3034a9b20706dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0790000000-19916045eff2f2277d60JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0fk9-0900000000-836aff54cb90ce573db4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0900000000-cb1ef888d872056bce56JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00di-0900000000-97660ea43493fa2fa991JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-05fr-0900000000-407e81a32dbf5eb07134JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0900000000-743290b40f399a527da5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0900000000-667b9ae1f4c499b8cef6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0900000000-c6bf89700e58ad9aff83JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-1900000000-b644d0eec4449bae7675JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01t9-2900000000-d794028d708aa5c5d04fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03gi-5900000000-b2b0a6ddec7e2e91e8c4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-2090000000-d30081dd79d918431d63JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-4290000000-42d4b65040e25cf691f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9500000000-50cff13af2772ff9bd1eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0090000000-65bdc875b481997f35b0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0090000000-cbe4e5e680eed587e220JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-007c-9200000000-9732b6de02e7378e613cJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureRapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.
Mechanism of ToxicityZidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active 5ду_-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase ‘± and ‘_.
MetabolismHepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV). UGT2B7 is the primary UGT isoform that is responsible for glucuronidation. Compared to zidovudine, GZDV's area under the curve is approximately 3-fold greater. The cytochrome P450 isozymes are responsible for the reduction of the azido moiety to form 3'-amino-3'- deoxythymidine (AMT). Route of Elimination: As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV. Half Life: Elimination half life, HIV-infected patients, IV administration = 1.1 hours (range of 0.5 - 2.9 hours)
Toxicity ValuesLD50 is 3084 mg/kg (orally in mice).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (7)
Uses/SourcesUsed in combination with other antiretroviral agents for the treatment of human immunovirus (HIV) infections.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include fatigue, headache, nausea, and vomiting.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00495
HMDB IDHMDB14638
PubChem Compound ID35370
ChEMBL IDCHEMBL129
ChemSpider ID32555
KEGG IDC07210
UniProt IDNot Available
OMIM ID
ChEBI ID10110
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDAZZ
ACToR IDNot Available
Wikipedia LinkZidovudine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. [7508227 ]
  2. Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. [3072667 ]
  3. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al.: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80. [7935654 ]
  4. Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. [1699273 ]
  5. Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S: 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096-100. [2413459 ]
  6. Court MH, Krishnaswamy S, Hao Q, Duan SX, Patten CJ, Von Moltke LL, Greenblatt DJ: Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism. Drug Metab Dispos. 2003 Sep;31(9):1125-33. [12920168 ]
  7. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Trna binding
Specific Function:
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.
Gene Name:
TERT
Uniprot ID:
O14746
Molecular Weight:
126995.435 Da
References
  1. Leeansyah E, Cameron PU, Solomon A, Tennakoon S, Velayudham P, Gouillou M, Spelman T, Hearps A, Fairley C, Smit de V, Pierce AB, Armishaw J, Crowe SM, Cooper DA, Koelsch KK, Liu JP, Chuah J, Lewin SR: Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. J Infect Dis. 2013 Apr;207(7):1157-65. doi: 10.1093/infdis/jit006. Epub 2013 Jan 9. [23303810 ]