ArticleAntimicrobial agents and chemotherapy2016
Intracellular Activation of Tenofovir Alafenamide and the Effect of Viral and Host Protease Inhibitors.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- Effect of Tenofovir Alafenamide Fumarate on the outcomes of hospitalized COVID-19 patients: a prospective, block-balanced, open-label, randomized controlled trial.BMC pharmacology & toxicology · 2024Trial
- Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues.The Journal of antimicrobial chemotherapy · 2017Trial
- An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics.medRxiv : the preprint server for health sciences · 2026Article
- Recommendations for Interpreting Intraerythrocytic Tenofovir Diphosphate and Emtricitabine Triphosphate for HIV-1 Preexposure Prophylaxis Adherence Assessment.Journal of acquired immune deficiency syndromes (1999) · 2025Review
- The use of phosphotriesterase in the synthesis of enantiomerically pure ProTide prodrugs.Chemico-biological interactions · 2025Review
- Carboxylesterase Factors Influencing the Therapeutic Activity of Common Antiviral Medications Used for SARS-CoV-2 Infection.Pharmaceutics · 2025Review
- Cellular pharmacology of tenofovir alafenamide and emtricitabine in neutrophils and platelets in people with and without HIV.The Journal of antimicrobial chemotherapy · 2025Article
- [Study on the efficacy and safety profile of tenofovir alafenamide fumarate in the treatment of patients with decompensated hepatitis B cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons With HIV Receiving Tenofovir Alafenamide and Emtricitabine-Based Antiretroviral Therapy (QUANTI-TAF).Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Observational
- Regulation of Human Hydrolases and Its Implications in Pharmacokinetics and Pharmacodynamics.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Effect of P-glycoprotein and Cotreatment with Sofosbuvir on the Intestinal Permeation of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide Fumarate.Pharmaceutical research · 2023Article
- Fundamental aspects of long-acting tenofovir alafenamide delivery from subdermal implants for HIV prophylaxis.Scientific reports · 2022Article
- Contributions of Cathepsin A and Carboxylesterase 1 to the Hydrolysis of Tenofovir Alafenamide in the Human Liver, and the Effect of CES1 Genetic Variation on Tenofovir Alafenamide Hydrolysis.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Synthesis and Metabolism of BTN3A1 Ligands: Studies on Diene Modifications to the Phosphoantigen Scaffold.ACS medicinal chemistry letters · 2022Article
- Phosphoryl Prodrugs: Characteristics to Improve Drug Development.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
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- Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.Frontiers in chemistry · 2022Review
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- Key Metabolic Enzymes Involved in Remdesivir Activation in Human Lung Cells.Antimicrobial agents and chemotherapy · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tenofovir alafenamide fumarate (TAF) is an oral phosphonoamidate prodrug of the HIV reverse transcriptase nucleotide inhibitor tenofovir (TFV). Previous studies suggested a principal role for the lysosomal serine protease cathepsin A (CatA) in the intracellular activation of TAF. Here we further investigated the role of CatA and other human hydrolases in the metabolism of TAF. Overexpression of CatA or liver carboxylesterase 1 (Ces1) in HEK293T cells increased intracellular TAF hydrolysis 2- and 5-fold, respectively. Knockdown of CatA expression with RNA interference (RNAi) in HeLa cells reduced intracellular TAF metabolism 5-fold. Additionally, the anti-HIV activity and the rate of CatA hydrolysis showed good correlation within a large set of TFV phosphonoamidate prodrugs. The covalent hepatitis C virus (HCV) protease inhibitors (PIs) telaprevir and boceprevir potently inhibited CatA-mediated TAF activation (50% inhibitory concentration [IC50] = 0.27 and 0.16 μM, respectively) in vitro and also reduced its anti-HIV activity in primary human CD4(+) T lymphocytes (21- and 3-fold, respectively) at pharmacologically relevant concentrations. In contrast, there was no inhibition of CatA or any significant effect on anti-HIV activity of TAF observed with cobicistat, noncovalent HIV and HCV PIs, or various prescribed inhibitors of host serine proteases. Collectively, these studies confirm that CatA plays a pivotal role in the intracellular metabolism of TAF, whereas the liver esterase Ces1 likely contributes to the hepatic activation of TAF. Moreover, this work demonstrates that a wide range of viral and host PIs, with the exception of telaprevir and boceprevir, do not interfere with the antiretroviral activity of TAF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.