ArticleScience (New York, N.Y.)2008
PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release.
Article in Science (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01571414 (A Phase I, Three-Arm Safety, Tolerability, and Pharmacokinetic Interaction Study of PA-824, an Investigational Nitroimidazole for the Treatment of Tuberculosis, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin), which is not on this map. Cited by 288 papers, 1 of them a synthesis that pooled it.
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.
A Phase I, Three-Arm Safety, Tolerability, and Pharmacokinetic Interaction Study of PA-824, an Investigational Nitroimidazole for the Treatment of Tuberculosis, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin
Who cites it
288 citing papers in PubMed, 1 synthesis or guideline pooled it, 629 citations in OpenAlex.
- Impact of all-oral bedaquiline-based shorter regimens in the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis.BMJ global health · 2025Pooled it
- Pharmacokinetics, bactericidal activity and toxicity of short oral regimens for rifampicin-resistant tuberculosis treatment.Nature communications · 2026Trial
- Population pharmacokinetics and target attainment of pretomanid in rifampicin-resistant tuberculosis patients.Scientific reports · 2026Trial
- A novel antituberculosis agent exhibits potent clinical efficacy and good safety profile: an open-label, randomized-controlled, multicenter, phase 2a trial.Signal transduction and targeted therapy · 2025Trial
- Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.The New England journal of medicine · 2022Trial
- Phase 1 Study of the Effects of the Tuberculosis Treatment Pretomanid, Alone and in Combination With Moxifloxacin, on the QTc Interval in Healthy Volunteers.Clinical pharmacology in drug development · 2021Trial
- Pretomanid Pharmacokinetics in the Presence of Rifamycins: Interim Results from a Randomized Trial among Patients with Tuberculosis.Antimicrobial agents and chemotherapy · 2021Trial
- Treatment of Highly Drug-Resistant Pulmonary Tuberculosis.The New England journal of medicine · 2020Trial
- Mechanism of the M. tuberculosis DprE1-DprE2 epimerase complex and inhibition by anti-tubercular drugs.Nature chemical biology · 2026Article
- Molecular Mechanisms Underlying Antimicrobial Resistance in Mycobacteria.International journal of molecular sciences · 2026Review
- Synthesis of 4-Aminoindole-Containing Cephalosporin Prodrugs and Their Biological Activity againstACS infectious diseases · 2026Article
- Exploiting DprE2 pathway redundancy to enhance potency and overcome resistance to pretomanid in Mycobacterium tuberculosis.npj antimicrobials and resistance · 2026Article
- Breaking barriers in extensively drug-resistant TB: pretomanid-centred long regimen achieves cure in a bedaquiline-resistant strain.IJTLD open · 2026Article
- Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations.Microorganisms · 2026Review
- Review
- Novel glycine amides, semicarbazides and fluoroallylamines as inhibitors of the amine oxidase vascular adhesion protein-1 (VAP-1).RSC medicinal chemistry · 2026Article
- A bactericidal tuberculosis drug regimen driven by inhibition of the terminal oxidases by pretomanid.EMBO molecular medicine · 2026Article
- Diaryl-Aminoindazole with Extensive In Vitro Mycobactericidal Activity Dependent on Exposure to Reactive Nitrogen Species.ACS infectious diseases · 2026Article
- A Series of Pyrazolo-Quinazoline Amines Inhibits the CytochromeJournal of medicinal chemistry · 2026Article
- Beyond culturability: VBNC-like and differentially culturableFrontiers in cellular and infection microbiology · 2026Review
228 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Bicyclic nitroimidazoles, including PA-824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin-dependent nitroreductase (Ddn) that converts PA-824 into three primary metabolites; the major one is the corresponding des-nitroimidazole (des-nitro). When derivatives of PA-824 were used, the amount of des-nitro metabolite formed was highly correlated with anaerobic killing of Mycobacterium tuberculosis (Mtb). Des-nitro metabolite formation generated reactive nitrogen species, including nitric oxide (NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system.
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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.