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Showing drug card for Tenofovir (DB00300)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:42
Primary Accession Number DB00300
Secondary Accession Number
  • APRD01248
Name Tenofovir
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Tenofovir, marketed by Gilead Sciences under the trade name Viread®, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. [Wikipedia]
Synonyms
  1. D,L-Tenofovir
  2. PMPA
  3. TDF
  4. Tenofovir disoproxil
  5. Tenofovir disoproxil fumarate
Brand Names
  1. Apropovir
  2. Viread
Brand Mixtures
  1. Atripla (tenofovir + emtricitabine + efavirenz)
  2. Truvada (tenofovir + emtricitabine)
Chemical IUPAC Name [(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid
Chemical Formula C9H14N5O4P
Chemical Structure Structure
CAS Registry Number 147127-20-6
InChI Identifier InChI=1/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m1/s1/f/h15-16H,10H2
InChI Key SGOIRFVFHAKUTI-DIXDEQOFDQ
KEGG Drug D01982 Link Image
KEGG Compound Not Available
PubChem Compound 464205 Link Image
PubChem Substance 699321 Link Image
ChEBI ID Not Available
PharmGKB ID PA10204 Link Image
HET ID TFO Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02247128 Link Image
RxList Link http://www.rxlist.com/cgi/generic/viread.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/vir1605.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Tenofovir Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 287.2123
Monoisotopic Molecular Weight 287.0783
State Solid
Melting Point 276-280oC
Experimental Water Solubility 13.4 mg/mL in distilled water at 25oC (disoproxil fumarate salt) Source: PhysProp
Predicted Water Solubility 1.87e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.6 Source: PhysProp
Predicted LogP -1.50 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.19 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@H](CN1C=NC2=C(N)N=CN=C12)OCP(O)(O)=O
Canonical SMILES CC(CN1C=NC2=C(N)N=CN=C12)OCP(O)(O)=O
Drug Category
  • Anti-HIV Agents
  • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors
ATC Codes
AHFS Codes
  • 08:18.08.20
Indication For use, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.
Pharmacology Tenofovir belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NtRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. Tenofovir is currently in late-stage clinical trials for the treatment of hepatitis B. Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α, β, and mitochondrial DNA polymerase γ.
Mechanism of Action Tenofovir inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination.
Absorption The oral bioavailability in fasted patients is approximately 25%. Administration of food (high fat meal containing 40 to 50% fat) increases the oral bioavailability, with an increase in the AUC of approximately 40%.
Toxicity Limited clinical experience at doses higher than the therapeutic dose of tenofovir 300 mg is available. In Study 901 tenofovir disoproxil fumarate 600 mg was administered to 8 patients orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known.
Protein Binding Very low: < 0.7% to human plasma proteins and < 7.2% to serum proteins
Biotransformation Neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes.
Half Life Approximately 17 hours.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Atazanavir Concomitant therapy may result in decreased serum levels of Atazanavir and increased levels of Tenofovir. Concomitant therapy should only be used with the inclusion of Ritonavir.
Didanosine Tenofovir may decrease the therapeutic effects and increase the adverse effects of Didanosine. Monitor for changes in virologic response and Didanosine toxicity during concomitant therapy.
Food Interactions Not Available
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Human Immunodeficiency Virus
Targets
  1. Gag-Pol polyprotein
Drug Target 1 [top]
Target 1 ID 864
Target 1 Name Gag-Pol polyprotein
Target 1 Synonyms
  1. Pr160Gag-Pol
Target 1 Gene Name gag
Target 1 Protein Sequence >Gag-Pol polyprotein 
GARASVLSGGELDKWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQIL
GQLQPSLQTGSEELRSLYNTVATLYCVHQRIDVKDTKEALEKIEEEQNKSKKKAQQAAAA
AGTGNSSQVSQNYPIVQNLQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGA
TPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGT
TSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDR
FYKTLRAEQASQDVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHK
ARVLAEAMSQVTNPANIMMQRGNFRNQRKTVKCFNCGKEGHIAKNCRAPRKKGCWRCGRE
GHQMKDCTERQANFLREDLAFLQGKAREFSSEQTRANSPTRRELQVWGGENNSLSEAGAD
RQGTVSFNFPQITLWQRPLVTIRIGGQLKEALLDTGADDTVLEEMNLPGKWKPKMIGGIG
GFIKVRQYDQIPVEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKL
KPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWR
KLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDKDFRKYTAFTI
PSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFRKQNPDIVIYQYMDDLYVGSD
LEIGQHRTKIEELRQHLLRWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIMLPEKDSW
TVNDIQKLVGKLNWASQIYAGIKVKQLCKLLRGTKALTEVIPLTEEAELELAENREILKE
PVHEVYYDPSKDLVAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAV
QKVSTESIVIWGKIPKFKLPIQKETWEAWWMEYWQATWIPEWEFVNTPPLVKLWYQLEKE
PIVGAETFYVDGAANRETKLGKAGYVTDRGRQKVVSIADTTNQKTELQAIHLALQDSGLE
VNIVTDSQYALGIIQAQPDKSESELVSQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLV
SAGIRKVLFLNGIDKAQEEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHG
QVDCSPGIWQLDCTHLEGKIILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKT
IHTDNGSNFTSTTVKAACWWAGIKQEFGIPYNPQSQGVVESMNNELKKIIGQVRDQAEHL
KTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDNKD
PLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED
Target 1 Number of Residues 1459
Target 1 Molecular Weight 161886
Target 1 Theoretical pI 9.02
Target 1 GO Classification
Function
RNA binding
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
RNA-directed DNA polymerase activity
DNA binding
hydrolase activity, acting on ester bonds
nuclease activity
endonuclease activity
endoribonuclease activity
endoribonuclease activity, producing 5'-phosphomonoesters
ribonuclease H activity
nucleic acid binding
hydrolase activity
peptidase activity
endopeptidase activity
aspartic-type endopeptidase activity
structural molecule activity
binding
ion binding
cation binding
transition metal ion binding
zinc ion binding
catalytic activity
integrase activity
Process
DNA replication
RNA-dependent DNA replication
DNA recombination
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA integration
viral life cycle
Component
Not Available
Target 1 General Function Involved in RNA binding
Target 1 Specific Function Integrase performs the integration of the newly synthesized dsDNA copy of the viral genome into the host chromosome. The integrated DNA is called provirus
Target 1 Pathways
Name SMPDB Link KEGG Link
DNA polymerase map03030 Link Image
Purine metabolism SMP00050 Link Image map00230 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 1 Reactions
  • deoxynucleoside triphosphate + DNAn = diphosphate + DNAn+1
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 328661 Link Image
Target 1 UniProtKB/Swiss-Prot ID P03369 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name POL_HV1A2 Link Image
Target 1 PDB ID 1VRU Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Nucleus. Cytoplasm (By similarity). Following virus entry, the nuclear localization signal (NLS) of
Target 1 Gene Sequence >3012 bp 
TTTTTTAGGGAAGATCTGGCCTTCCTACAAGGGAAGGCCAGGGAATTTTCTTCAGAGCAG
ACCAGAGCCAACAGCCCCACCAGAAGAGAGCTTCAGGTTTGGGGAGGAGAAAACAACTCC
CTCTCAGAAGCAGGAGCCGATAGACAAGGAACTGTATCCTTTAACTTCCCTCAGATCACT
CTTTGGCAACGACCCCTCGTCACAATAAGGATAGGGGGGCAACTAAAGGAAGCTCTATTA
GATACAGGAGCAGATGATACAGTATTAGAAGAAATGAATTTGCCAGGAAAATGGAAACCA
AAAATGATAGGGGGAATTGGAGGTTTTATCAAAGTAAGACAGTACGATCAGATACCTGTA
GAAATCTGTGGACATAAAGCTATAGGTACAGTATTAGTAGGACCTACACCTGTCAACATA
ATTGGAAGAAATCTGTTGACTCAGATTGGTTGTACTTTAAATTTCCCCATTAGTCCTATT
GAAACTGTACCAGTAAAATTAAAGCCAGGAATGGATGGCCCAAAAGTTAAGCAATGGCCA
TTGACAGAAGAAAAAATAAAAGCATTAGTAGAGATATGTACAGAAATGGAAAAGGAAGGG
AAAATTTCAAAAATTGGGCCTGAAAATCCATACAATACTCCAGTATTTGCTATAAAGAAA
AAAGACAGTACTAAATGGAGAAAACTAGTAGATTTCAGAGAACTTAATAAAAGAACTCAA
GACTTCTGGGAAGTTCAGTTAGGAATACCACACCCCGCAGGGTTAAAAAAGAAAAAATCA
GTAACAGTATTGGATGTGGGTGATGCATACTTTTCAGTTCCCTTAGATAAAGACTTTAGA
AAGTATACTGCATTTACCATACCTAGTATAAACAATGAGACACCAGGGATTAGATATCAG
TACAATGTGCTGCCACAGGGATGGAAAGGATCACCAGCAATATTCCAAAGTAGCATGACA
AAAATCTTAGAGCCTTTTAGAAAACAGAATCCAGACATAGTTATCTATCAATACATGGAT
GATTTGTATGTAGGATCTGACTTAGAAATAGGGCAGCATAGAACAAAAATAGAGGAACTG
AGACAGCATCTGTTGAGGTGGGGATTTACCACACCAGACAAAAAACATCAGAAAGAACCT
CCATTCCTTTGGATGGGTTATGAACTCCATCCTGATAAATGGACAGTACAGCCTATAATG
CTGCCAGAAAAAGACAGCTGGACTGTCAATGACATACAGAAGTTAGTGGGAAAATTGAAT
TGGGCAAGTCAGATTTATGCAGGGATTAAAGTAAAGCAGTTATGTAAACTCCTTAGAGGA
ACCAAAGCACTAACAGAAGTAATACCACTAACAGAAGAAGCAGAGCTAGAACTGGCAGAA
AACAGGGAGATTCTAAAAGAACCAGTACATGAAGTATATTATGACCCATCAAAAGACTTA
GTAGCAGAAATACAGAAGCAGGGGCAAGGCCAATGGACATATCAAATTTATCAAGAGCCA
TTTAAAAATCTGAAAACAGGAAAGTATGCAAGGATGAGGGGTGCCCACACTAATGATGTA
AAACAGTTAACAGAGGCAGTGCAAAAAGTATCCACAGAAAGCATAGTAATATGGGGAAAG
ATTCCTAAATTTAAACTACCCATACAAAAGGAAACATGGGAAGCATGGTGGATGGAGTAT
TGGCAAGCTACCTGGATTCCTGAGTGGGAGTTTGTCAATACCCCTCCCTTAGTGAAATTA
TGGTACCAGTTAGAGAAAGAACCCATAGTAGGAGCAGAAACTTTCTATGTAGATGGGGCA
GCTAATAGGGAGACTAAATTAGGAAAAGCAGGATATGTTACTGACAGAGGAAGACAAAAA
GTTGTCTCCATAGCTGACACAACAAATCAGAAGACTGAATTACAAGCAATTCATCTAGCT
TTGCAGGATTCGGGATTAGAAGTAAACATAGTAACAGACTCACAATATGCATTAGGAATC
ATTCAAGCACAACCAGATAAGAGTGAATCAGAGTTAGTCAGTCAAATAATAGAGCAGTTA
ATAAAAAAGGAAAAGGTCTACCTGGCATGGGTACCAGCACACAAAGGAATTGGAGGAAAT
GAACAAGTAGATAAATTAGTCAGTGCTGGAATCAGGAAAGTACTATTTTTGAATGGAATA
GATAAGGCCCAAGAAGAACATGAGAAATATCACAGTAATTGGAGAGCAATGGCTAGTGAT
TTTAACCTGCCACCTGTAGTAGCAAAAGAAATAGTAGCCAGCTGTGATAAATGTCAGCTA
AAAGGAGAAGCCATGCATGGACAAGTAGACTGTAGTCCAGGAATATGGCAACTAGATTGT
ACACATCTAGAAGGAAAAATTATCCTGGTAGCAGTTCATGTAGCCAGTGGATATATAGAA
GCAGAAGTTATTCCAGCAGAGACAGGGCAGGAAACAGCATATTTTCTCTTAAAATTAGCA
GGAAGATGGCCAGTAAAAACAATACATACAGACAATGGCAGCAATTTCACCAGTACTACG
GTTAAGGCCGCCTGTTGGTGGGCAGGGATCAAGCAGGAATTTGGCATTCCCTACAATCCC
CAAAGTCAAGGAGTAGTAGAATCTATGAATAATGAATTAAAGAAAATTATAGGACAGGTA
AGAGATCAGGCTGAACACCTTAAGACAGCAGTACAAATGGCAGTATTCATCCACAATTTT
AAAAGAAAAGGGGGGATTGGGGGATACAGTGCAGGGGAAAGAATAGTAGACATAATAGCA
ACAGACATACAAACTAAAGAACTACAAAAGCAAATTACAAAAATTCAAAATTTTCGGGTT
TATTACAGGGACAACAAAGATCCCCTTTGGAAAGGACCAGCAAAGCTTCTCTGGAAAGGT
GAAGGGGCAGTAGTAATACAAGATAATAGTGACATAAAAGTAGTGCCAAGAAGAAAAGCA
AAAATCATTAGGGATTATGGAAAACAGATGGCAGGTGATGATTGTGTGGCAAGTAGACAG
GATGAGGATTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Tyndall JD, Reid RC, Tyssen DP, Jardine DK, Todd B, Passmore M, March DR, Pattenden LK, Bergman DA, Alewood D, Hu SH, Alewood PF, Birch CJ, Martin JL, Fairlie DP: Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease. J Med Chem. 2000 Sep 21;43(19):3495-504. [PubMed Link Image]
  2. Prabu-Jeyabalan M, Nalivaika E, Schiffer CA: Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Structure. 2002 Mar;10(3):369-81. [PubMed Link Image]
  3. Jacks T, Power MD, Masiarz FR, Luciw PA, Barr PJ, Varmus HE: Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature. 1988 Jan 21;331(6153):280-3. [PubMed Link Image]
  4. Wlodawer A, Miller M, Jaskolski M, Sathyanarayana BK, Baldwin E, Weber IT, Selk LM, Clawson L, Schneider J, Kent SB: Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science. 1989 Aug 11;245(4918):616-21. [PubMed Link Image]
  5. Sanchez-Pescador R, Power MD, Barr PJ, Steimer KS, Stempien MM, Brown-Shimer SL, Gee WW, Renard A, Randolph A, Levy JA, et al.: Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985 Feb 1;227(4686):484-92. [PubMed Link Image]
  6. Rose RB, Craik CS, Douglas NL, Stroud RM: Three-dimensional structures of HIV-1 and SIV protease product complexes. Biochemistry. 1996 Oct 1;35(39):12933-44. [PubMed Link Image]
  7. Rutenber EE, McPhee F, Kaplan AP, Gallion SL, Hogan JC Jr, Craik CS, Stroud RM: A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere. Bioorg Med Chem. 1996 Sep;4(9):1545-58. [PubMed Link Image]
  8. Turner BG, Summers MF: Structural biology of HIV. J Mol Biol. 1999 Jan 8;285(1):1-32. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.