ArticleACS chemical biology2012
Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 252 citations in OpenAlex.
- Gaining insights into MmpL3: combining structural and computational approaches to unlock transport and inhibitor-binding mechanisms.Acta crystallographica. Section D, Structural biology · 2026Article
- Naturally occurring dinactin targets cpsA protein and kills Mycobacterium tuberculosis by disrupting the proton motive force.Communications biology · 2026Article
- Fighting the invader: strategies against intracellular bacteria.Frontiers in pharmacology · 2026Review
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Saskemycin, a potent and selective antimycobacterial agent targeting a unique site on the ribosome.Research square · 2025Article
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- Gliotoxin Production and Self-Defense in Filamentous Fungi.Annual review of microbiology · 2025Review
- Mutations in Genes with a Role in Cell Envelope Biosynthesis Render Gram-Negative Bacteria Highly Susceptible to the Anti-Infective Small Molecule D66.Microorganisms · 2025Article
- Investigating the unbinding mechanisms and kinetics of MmpL3 inhibitors: A computational study.Protein science : a publication of the Protein Society · 2025Article
- Tailored phenyl ureas eradicate drug-resistantChemical science · 2025Article
- Fluorescent Schiff Bases with Phenothiazine and Coumarin Moieties: Synthesis, Characterization, Photophysical, Electrochemical, Computational and Biological Studies.Journal of fluorescence · 2025Article
- Innovative perspectives on the discovery of small molecule antibiotics.npj antimicrobials and resistance · 2025Review
- Functions of nitroreductases in mycobacterial physiology and drug susceptibility.Journal of bacteriology · 2025Review
- Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Antitubercular Activities of Natural Products with Fused-Nitrogen-Containing Heterocycles.Pharmaceuticals (Basel, Switzerland) · 2024Review
- S288T mutation altering MmpL3 periplasmic domain channel and H-bond network: a novel dual drug resistance mechanism.Journal of molecular modeling · 2024Article
- TheMicrobiology spectrum · 2024Article
- Marine-Fungi-Derived Gliotoxin Promotes Autophagy to SuppressMarine drugs · 2023Article
- Gliotoxin and related metabolites as zinc chelators: implications and exploitation to overcome antimicrobial resistance.Essays in biochemistry · 2023Article
- High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.Metabolites · 2023Review
77 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
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite the urgent need for new antitubercular drugs, few are on the horizon. To combat the problem of emerging drug resistance, structurally unique chemical entities that inhibit new targets will be required. Here we describe our investigations using whole cell screening of a diverse collection of small molecules as a methodology for identifying novel inhibitors that target new pathways for Mycobacterium tuberculosis drug discovery. We find that conducting primary screens using model mycobacterial species may limit the potential for identifying new inhibitors with efficacy against M. tuberculosis. In addition, we confirm the importance of developing in vitro assay conditions that are reflective of in vivo biology for maximizing the proportion of hits from whole cell screening that are likely to have activity in vivo. Finally, we describe the identification and characterization of two novel inhibitors that target steps in M. tuberculosis cell wall biosynthesis. The first is a novel benzimidazole that targets mycobacterial membrane protein large 3 (MmpL3), a proposed transporter for cell wall mycolic acids. The second is a nitro-triazole that inhibits decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), an epimerase required for cell wall biosynthesis. These proteins are both among the small number of new targets that have been identified by forward chemical genetics using resistance generation coupled with genome sequencing. This suggests that methodologies currently employed for screening and target identification may lead to a bias in target discovery and that alternative methods should be explored.
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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.