tenofovir   Click here for help

GtoPdb Ligand ID: 10948

Abbreviated name: TDF
Synonyms: (R)-PMPA | PMPA | tenofovir (anhydrous)
Approved drug PDB Ligand
tenofovir is an approved drug
Compound class: Synthetic organic
Comment: Tenofovir is a nucleotide reverse transcriptase inhibitor (NtRTI) antiretroviral compound. The R-enantiomer, as shown here, is more effective at inhibiting retroviruses than the S-enantiomer [1]. Tenofovir has poor oral bioavailability and is delivered as either the prodrug tenofovir disoproxil fumarate (Viread®) or tenofovir alafenamide fumerate (Vemlidy®).
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 146.19
Molecular weight 287.08
XLogP -1.65
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C[C@H](Cn1cnc2c1ncnc2N)OCP(=O)(O)O
Isomeric SMILES C[C@H](Cn1cnc2c1ncnc2N)OCP(=O)(O)O
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
InChI Key SGOIRFVFHAKUTI-ZCFIWIBFSA-N
No information available.
Summary of Clinical Use Click here for help
Tenofovir is approved for the treatment of HIV (in combination with other antiretroviral agents) and chronic hepatitis B infections.
Compared to other nucleotide reverse transcriptase inhibitors, tenofovir demonstrates a favourable safety profile. Renal toxicity has been found to be a modest, but significant risk [2].

SARS-CoV-2 and COVID-19: A number of Phase 2/3 clinical trials are planned to evaluate the use of emtricitabine/tenofovir to prevent SARS-COV-2 transmission to healthcare professionals.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Tenofovir is an acyclic nucleotide diester analogue of adenosine 5'-monophosphate, reverse transciptase inhibitor, preventing viral replication.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04334928 Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel Phase 3 Interventional Plan Nacional sobre el Sida (PNS)
NCT04519125 Daily Regimen of Tenofovir/Emtricitabine as Prevention for COVID-19 in Health Care Personnel in Colombia Phase 2/Phase 3 Interventional Hospital Universitario San Ignacio
NCT04405271 TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study) Phase 3 Interventional Hospital Italiano de Buenos Aires
Pharmacokinetics Click here for help
Biotransformation/Metabolism
Bi-phosphorylation to the active compound tenofovir biphosphate.
Elimination
Tenofovir is eliminated in the urine by glomerular filtration and active tubular secretion.
Organ function impairment
In the kidney, tenofovir can cause proximal tubule dysfunction leading to Fanconi syndrome, acute tubular necrosis [7] and acute kidney injury (AKI) [5,7]. Severe AKI can cause chronic kidney disease (CKD) and even lead to end stage renal disease (ESRD).
Tenofovir can enter mitochondria of tubule cells where it inhibits mitochondrial DNA polymerase γ [3], giving structural mitochondrial abnormalities. This causes apoptosis via mitochondrial protein release. Injured proximal tubule cells are unable to reabsorb small molecules, secrete H+ or synthesize calcitriol [3]. Proximal tubule cell loss is caused from persistent injury, this decreases glomerular filtration rate and injures the kidney.
External links Click here for help
For extended ADME data see the following:

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