ArticlePloS one2015
Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 49 citations in OpenAlex.
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- Advances and challenges in drug repurposing in precision therapeutics of colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- Integrated genomics and chemical biology herald an era of sophisticated antibacterial discovery, from defining essential genes to target elucidation.Cell chemical biology · 2022Review
- Potency boost of aProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Identification of Potential Binders ofFrontiers in molecular biosciences · 2021Article
- Application of Computational Methods in Understanding Mutations inFrontiers in molecular biosciences · 2021Review
- Mycobacterial drug discovery.RSC medicinal chemistry · 2020Review
- Validation strategies for target prediction methods.Briefings in bioinformatics · 2020Review
- First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate.Journal of medicinal chemistry · 2020Article
- Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance.MedChemComm · 2019Review
- Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets.Scientific reports · 2018Article
- Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target.Parasitology · 2018Review
- Inhibiting mycobacterial tryptophan synthase by targeting the inter-subunit interface.Scientific reports · 2017Article
- Beyond the hype: deep neural networks outperform established methods using a ChEMBL bioactivity benchmark set.Journal of cheminformatics · 2017Article
- Predicting the Reliability of Drug-target Interaction Predictions with Maximum Coverage of Target Space.Scientific reports · 2017Article
- Learning from the past for TB drug discovery in the future.Drug discovery today · 2017Review
- Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB).Drug discovery today · 2017Review
- Target Identification ofFrontiers in pharmacology · 2017Article
- dfrA thyA Double Deletion in para-Aminosalicylic Acid-Resistant Mycobacterium tuberculosis Beijing Strains.Antimicrobial agents and chemotherapy · 2016Article
- THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria.Nature microbiology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The lack of success in target-based screening approaches to the discovery of antibacterial agents has led to reemergence of phenotypic screening as a successful approach of identifying bioactive, antibacterial compounds. A challenge though with this route is then to identify the molecular target(s) and mechanism of action of the hits. This target identification, or deorphanization step, is often essential in further optimization and validation studies. Direct experimental identification of the molecular target of a screening hit is often complex, precisely because the properties and specificity of the hit are not yet optimized against that target, and so many false positives are often obtained. An alternative is to use computational, predictive, approaches to hypothesize a mechanism of action, which can then be validated in a more directed and efficient manner. Specifically here we present experimental validation of an in silico prediction from a large-scale screen performed against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. The two potent anti-tubercular compounds studied in this case, belonging to the tetrahydro-1,3,5-triazin-2-amine (THT) family, were predicted and confirmed to be an inhibitor of dihydrofolate reductase (DHFR), a known essential Mtb gene, and already clinically validated as a drug target. Given the large number of similar screening data sets shared amongst the community, this in vitro validation of these target predictions gives weight to computational approaches to establish the mechanism of action (MoA) of novel screening hit.
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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.