ArticleScience translational medicine2015
Direct inhibitors of InhA are active against Mycobacterium tuberculosis.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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.
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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.
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Who cites it
57 citing papers in PubMed, 131 citations in OpenAlex.
- Optimizing the Antibiotic Potency and Metabolic Stability of Pyridomycin Using a Semisynthetic Approach.Journal of medicinal chemistry · 2026Article
- Discovery of novel InhA inhibitors through structural bioinformatics and machine learning-driven QSAR screening of natural products.Biology methods & protocols · 2026Article
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Structure-based design, synthesis, computational screening and biological evaluation of novel pyrrole fused pyrimidine derivatives targeting InhA enzyme.RSC advances · 2025Article
- An enoyl-ACP reductase inhibitor, NITD-916, expresses anti-Antimicrobial agents and chemotherapy · 2025Article
- Is Mycobacterial InhA a Suitable Target for Rational Drug Design?ChemMedChem · 2025Review
- The power of DNA-encoded chemical libraries in the battle against drug-resistant bacteria.RSC advances · 2025Review
- Experimental and theoretical studies on antituberculosis activity of different benzimidazole derivatives.Heliyon · 2025Article
- Catalase-peroxidase (KatG): a potential frontier in tuberculosis drug development.Critical reviews in biochemistry and molecular biology · 2024Review
- Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Design, synthesis and computational studies of new azaheterocyclic coumarin derivatives as anti-RSC advances · 2024Article
- Imidazoquinoline Derivatives as Potential Inhibitors of InhA Enzyme andMolecules (Basel, Switzerland) · 2024Article
- Inducing vulnerability to InhA inhibition restores isoniazid susceptibility in drug-resistantmBio · 2024Article
- In silico study of bioactive compounds derived from Indonesian marine invertebrates as a novel antituberculosis agent.Turkish journal of medical sciences · 2024Article
- Lipid-Centric Approaches in Combating Infectious Diseases: Antibacterials, Antifungals and Antivirals with Lipid-Associated Mechanisms of Action.Antibiotics (Basel, Switzerland) · 2023Review
- Tailoring selective triclosan azo-adducts: Design, synthesis, and anti-mycobacterial evaluation.Heliyon · 2023Article
- Review
- Evaluating the Impact of the Tyr158 pBiochemistry · 2023Article
- Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
Corrections and comments
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
New chemotherapeutic agents are urgently required to combat the global spread of multidrug-resistant tuberculosis (MDR-TB). The mycobacterial enoyl reductase InhA is one of the few clinically validated targets in tuberculosis drug discovery. We report the identification of a new class of direct InhA inhibitors, the 4-hydroxy-2-pyridones, using phenotypic high-throughput whole-cell screening. This class of orally active compounds showed potent bactericidal activity against common isoniazid-resistant TB clinical isolates. Biophysical studies revealed that 4-hydroxy-2-pyridones bound specifically to InhA in an NADH (reduced form of nicotinamide adenine dinucleotide)-dependent manner and blocked the enoyl substrate-binding pocket. The lead compound NITD-916 directly blocked InhA in a dose-dependent manner and showed in vivo efficacy in acute and established mouse models of Mycobacterium tuberculosis infection. Collectively, our structural and biochemical data open up new avenues for rational structure-guided optimization of the 4-hydroxy-2-pyridone class of compounds for the treatment of MDR-TB.
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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.