ReviewACS pharmacology & translational science2020
Metabolic Efficacy of Phosphate Prodrugs and the Remdesivir Paradigm.
Review in ACS pharmacology & translational science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 64 citations in OpenAlex.
- Benzoic Acid Derivatives Improve Plasma Stability of Diester Butyrophilin Ligand Prodrugs.Journal of medicinal chemistry · 2026Article
- The magic of mushrooms: psilocybin influences behavior in the mangrove rivulus fish,Frontiers in behavioral neuroscience · 2026Article
- Therapeutic Perspective of Prodrugs of Non-Steroidal Anti-Inflammatory Drugs and Antioxidants: An Approach to Reduce Toxicity and Enhance Efficacy.Current topics in medicinal chemistry · 2026Review
- Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase.Molecules (Basel, Switzerland) · 2025Article
- Synthesis and evaluation of triazole-containing aryl/acyloxy prodrugs of a BTN3A1 ligand.European journal of medicinal chemistry · 2025Article
- Mild and Chemoselective Triethylsilane-Mediated Debenzylation for Phosphate Synthesis.Organic letters · 2025Article
- Harnessing Oxetane and Azetidine Sulfonyl Fluorides for Opportunities in Drug Discovery.Journal of the American Chemical Society · 2024Article
- Novel Prodrug Strategies for the Treatment of Tuberculosis.Chemistry, an Asian journal · 2024Review
- Triazole-Based Thiamine Analogues as Inhibitors of Thiamine Pyrophosphate-Dependent Enzymes: 1,3-Dicarboxylate for Metal Binding.ACS omega · 2024Article
- Enhanced Plasma Stability and Potency of Aryl/Acyloxy Prodrugs of a BTN3A1 Ligand.ACS medicinal chemistry letters · 2024Article
- Applying a Tripodal Hexaurea Receptor for Binding to an Antitumor Drug, Combretastatin-A4 Phosphate.Materials (Basel, Switzerland) · 2024Article
- The landscape of small-molecule prodrugs.Nature reviews. Drug discovery · 2024Review
- Intracellular delivery and deep tissue penetration of nucleoside triphosphates using photocleavable covalently bound dendritic polycations.Chemical science · 2024Article
- Diester Prodrugs of a Phosphonate Butyrophilin Ligand Display Improved Cell Potency, Plasma Stability, and Payload Internalization.Journal of medicinal chemistry · 2023Article
- Peroxide-Mediated Release of Organophosphates from Boron-Containing Phosphotriesters: A New Class of Organophosphate Prodrugs.Organic letters · 2023Article
- Article
- A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein.EMBO molecular medicine · 2023Article
- PredPS: Attention-based graph neural network for predicting stability of compounds in human plasma.Computational and structural biotechnology journal · 2023Article
- Prodrugs of Nucleoside 5'-Monophosphate Analogues: Overview of the Recent Literature Concerning their Synthesis and Applications.Current medicinal chemistry · 2023Review
- How to use COVID-19 antiviral drugs in patients with chronic kidney disease.Frontiers in pharmacology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Drugs that contain phosphates (and phosphonates or phosphinates) have intrinsic absorption issues and are therefore often delivered in prodrug forms to promote their uptake. Effective prodrug forms distribute their payload to the site of the intended target and release it efficiently with minimal byproduct toxicity. The ability to balance unwanted payload release during transit with desired release at the site of action is critical to prodrug efficacy. Despite decades of research on prodrug forms, choosing the ideal prodrug form remains a challenge which is often solved empirically. The recent emergency use authorization of the antiviral remdesivir for COVID-19 exemplifies a new approach for delivery of phosphate prodrugs by parenteral dosing, which minimizes payload release during transit and maximizes tissue payload distribution. This review focuses on the role of metabolic activation in efficacy during oral and parenteral dosing of phosphate, phosphonate, and phosphinate prodrugs. Through examining prior structure-activity studies on prodrug forms and the choices that led to development of remdesivir and other clinical drugs and drug candidates, a better understanding of their ability to distribute to the planned site of action, such as the liver, plasma, PBMCs, or peripheral tissues, can be gained. The structure-activity relationships described here will facilitate the rational design of future prodrugs.
Identifiers
What OpenQuestion holds
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.