ArticleNature medicine2009
Synthetic EthR inhibitors boost antituberculous activity of ethionamide.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 172 citations in OpenAlex.
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- Alpibectir-Ethionamide combination (AlpE) for the treatment of tuberculosis.Nature communications · 2026Article
- Assessment of Innovative Dry Powders for Inhalation of a Synergistic Combination AgainstPharmaceutics · 2025Article
- Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning.BMJ global health · 2024Article
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- An Insight into Advances in Developing Nanotechnology Based Therapeutics, Drug Delivery, Diagnostics and Vaccines: Multidimensional Applications in Tuberculosis Disease Management.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Increased Susceptibility ofAntibiotics (Basel, Switzerland) · 2022Article
- Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.Antibiotics (Basel, Switzerland) · 2022Article
- Cosolvent Simulations with Fragment-Bound Proteins Identify Hot Spots to Direct Lead Growth.Journal of chemical theory and computation · 2022Article
- A combination screening to identify enhancers of para-aminosalicylic acid against Mycobacterium tuberculosis.Scientific reports · 2022Article
- HowFrontiers in cellular and infection microbiology · 2022Review
- Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- "Upcycling" known molecules and targets for drug-resistant TB.Frontiers in cellular and infection microbiology · 2022Article
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- Molecular Design in Practice: A Review of Selected Projects in a French Research Institute That Illustrates the Link between Chemical Biology and Medicinal Chemistry.Molecules (Basel, Switzerland) · 2021Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
The side effects associated with tuberculosis therapy bring with them the risk of noncompliance and subsequent drug resistance. Increasing the therapeutic index of antituberculosis drugs should thus improve treatment effectiveness. Several antituberculosis compounds require in situ metabolic activation to become inhibitory. Various thiocarbamide-containing drugs, including ethionamide, are activated by the mycobacterial monooxygenase EthA, the production of which is controlled by the transcriptional repressor EthR. Here we identify drug-like inhibitors of EthR that boost the bioactivation of ethionamide. Compounds designed and screened for their capacity to inhibit EthR-DNA interaction were co-crystallized with EthR. We exploited the three-dimensional structures of the complexes for the synthesis of improved analogs that boosted the ethionamide potency in culture more than tenfold. In Mycobacterium tuberculosis-infected mice, one of these analogs, BDM31343, enabled a substantially reduced dose of ethionamide to lessen the mycobacterial load as efficiently as the conventional higher-dose treatment. This provides proof of concept that inhibiting EthR improves the therapeutic index of thiocarbamide derivatives, which should prompt reconsideration of their use as first-line drugs.
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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.