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targets (1) enzymes (1)
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Identification
Name Tenofovir
Accession Number DB00300 (APRD01248)
Type small molecule
Groups approved
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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • D,L-Tenofovir
  • PMPA
  • TDF
  • Tenofovir disoproxil
  • Tenofovir disoproxil fumarate
Brand names
  • Apropovir
  • Viread
Brand name mixtures
  • Atripla (tenofovir + emtricitabine + efavirenz)
  • Truvada (tenofovir + emtricitabine)
Categories
  • Anti-HIV Agents
  • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors
CAS number 147127-20-6
Weight Average: 287.2123
Monoisotopic: 287.078340473
Chemical Formula C9H14N5O4P
InChI Key InChIKey=SGOIRFVFHAKUTI-ZCFIWIBFSA-N
InChI
InChI=1S/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
Plain Text
IUPAC Name
({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
SMILES
C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Purines and Purine Derivatives
Substructures
  • Hydroxy Compounds
  • Phosphonic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Ethers
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Phosphinic Acids and Derivatives
  • Cyanamides
Pharmacology
Indication For use, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.
Pharmacodynamics 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. Specifically, the drugs are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NtRTIs (nucleoside/tide reverse transcriptase inhibitors) lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors.
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%.
Volume of distribution
  • 1.3 ± 0.6 L/kg [tenofovir 1.0 mg/kg]
  • 1.2 ± 0.4 L/kg [tenofovir 3.0 mg/kg]
Protein binding Very low: < 0.7% to human plasma proteins and < 7.2% to serum proteins
Metabolism

Neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes.
Route of elimination Not Available
Half life Approximately 17 hours.
Clearance Not Available
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.
Affected organisms
  • Human Immunodeficiency Virus
Pathways
Pathway Name SMPDB ID
Smp00419 Tenofovir Pathway SMP00419
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
  • Gilead Sciences, Inc.
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Viread 300 mg tablet 33.95 USD tablet
Patents
Country Patent Number Approved Expires
United States 5922695 1997-07-25 2017-07-25
Canada 2298059 2008-12-30 2018-07-23
Canada 2261619 2006-05-23 2017-07-25
Properties
State solid
Melting point 276-280oC
Experimental Properties
Property Value Source
water solubility 13.4 mg/mL in distilled water at 25oC (disoproxil fumarate salt) PhysProp
logP -1.6 PhysProp
Predicted Properties
Property Value Source
water solubility 1.87e+00 g/l ALOGPS
logP -1.51 ALOGPS
logP -3.96 ChemAxon Molconvert
logS -2.19 ALOGPS
pKa 7.91 ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 136.38 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 67.54 ChemAxon Molconvert
polarizability 25.54 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01982 Link_out
PubChem Compound 464205 Link_out
PubChem Substance 46508131 Link_out
ChemSpider 408154 Link_out
Therapeutic Targets Database DAP001430 Link_out
PharmGKB PA10204 Link_out
HET TFO Link_out
Drug Product Database 2247128 Link_out
RxList http://www.rxlist.com/cgi/generic/viread.htm Link_out
Drugs.com http://www.drugs.com/cdi/tenofovir.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/vir1605.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Tenofovir Link_out
ATC Codes
  • J05AF07
AHFS Codes
  • 08:18.08.20
PDB Entries Not Available
FDA label show (286.7 KB)
MSDS show (57.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. De Clercq E: Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33. Pubmed
  2. De Clercq E: A 40-Year Journey in Search of Selective Antiviral Chemotherapy. Annu Rev Pharmacol Toxicol. 2010 Jan 18. Pubmed
  3. Molina JM, Cox SL: Emtricitabine: a novel nucleoside reverse transcriptase inhibitor. Drugs Today (Barc). 2005 Apr;41(4):241-52. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: inhibitor

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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:37

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.