Tmic
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Record Information
Version2.0
Creation Date2014-09-11 05:15:56 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4772
Identification
Common NameStavudine
ClassSmall Molecule
DescriptionA dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.
Compound Type
  • Amide
  • Anti-HIV Agent
  • Antimetabolite
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Reverse Transcriptase Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine
2',3'-Didehydro-3'-deoxythimidine
3'-Deoxy-2'-thymidinene
Actastav
Ai Fu Ding
Avostav
d4T
Estavudina
Estavudox
Exvihr
Flamistav
Landstav
Lion
Mai Si Ting
S.T.V.
Sanilvudine
Sazi
Stadine
Stag
Stamar
Stavex
Stavir
Stavubergen
Stavudin
Stavudinum
STV
Zerit
Zerit XR
Chemical FormulaC10H12N2O4
Average Molecular Mass224.213 g/mol
Monoisotopic Mass224.080 g/mol
CAS Registry Number3056-17-5
IUPAC Name1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
Traditional Namestavudine
SMILES[H][C@]1(CO)O[C@]([H])(C=C1)N1C=C(C)C(O)=NC1=O
InChI IdentifierInChI=1S/C10H12N2O4/c1-6-4-12(10(15)11-9(6)14)8-3-2-7(5-13)16-8/h2-4,7-8,13H,5H2,1H3,(H,11,14,15)/t7-,8+/m0/s1
InChI KeyInChIKey=XNKLLVCARDGLGL-JGVFFNPUSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as nucleoside and nucleotide analogues. These are analogues of nucleosides and nucleotides. These include phosphonated nucleosides, C-glycosylated nucleoside bases, analogues where the sugar unit is a pyranose, and carbocyclic nucleosides, among others.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassNucleoside and nucleotide analogues
Sub ClassNot Available
Direct ParentNucleoside and nucleotide analogues
Alternative Parents
Substituents
  • Pyrimidone
  • Hydropyrimidine
  • Pyrimidine
  • Dihydrofuran
  • Vinylogous amide
  • Heteroaromatic compound
  • Lactam
  • Urea
  • Organoheterocyclic compound
  • Azacycle
  • Oxacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
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 Point159-160°C
Boiling PointNot Available
Solubility5-10 g/100 mL at 21°C
LogP-0.72
Predicted Properties
PropertyValueSource
Water Solubility40.5 g/LALOGPS
logP-0.73ALOGPS
logP-0.23ChemAxon
logS-0.74ALOGPS
pKa (Strongest Acidic)9.95ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.87 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity55.32 m³·mol⁻¹ChemAxon
Polarizability21.33 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-9710000000-ec1b8accee7609d895afView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0fi9-9710000000-a08eaef1e27e4362b56eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-a15778802feedb7e8702View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-5900000000-1e77dd699ba1244d96ddView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a7j-9600000000-42ce2a756eceb750ac46View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00c0-2940000000-3e2b43ac1b4b3b11d540View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01di-3920000000-0a634444532bc0df9549View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9200000000-5a3e9da67f3d054c39c8View in MoNA
Toxicity Profile
Route of ExposureFollowing oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%).
Mechanism of ToxicityStavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
MetabolismPhosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase. Half Life: 0.8-1.5 hours (in adults)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of human immunovirus (HIV) infections.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSide effects include peripheral neuropathy tingling, burning, numbness, or pain in the hands or feet), fatal lactic acidosis has been reported in patients treated with stavudine (ZERIT) in combination with other antiretroviral agents, severe liver enlargement, inflammation (pain and swelling) of the liver, and liver failure.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00649
HMDB IDHMDB14787
PubChem Compound ID18283
ChEMBL IDCHEMBL991
ChemSpider ID17270
KEGG IDC07312
UniProt IDNot Available
OMIM ID
ChEBI ID63581
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkStavudine
References
Synthesis Reference

Purna Chandra Ray, Jagan Mohana Chary Tummanapalli, Seeta Ramanjaneyulu Gorantla, “Process for the Large Scale Production of Stavudine.” U.S. Patent US20080312428, issued December 18, 2008.

MSDSLink
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0302 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]