ArticleJournal of chemical information and modeling2015
A virtual screen discovers novel, fragment-sized inhibitors of Mycobacterium tuberculosis InhA.
Article in Journal of chemical information and modeling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Discovery of the small molecular inhibitors against TRPV6 as potential anti-cancer agents by structural based virtual screening.Frontiers in chemistry · 2026Article
- Discovery of New Zika Protease and Polymerase Inhibitors through the Open Science Collaboration Project OpenZika.Journal of chemical information and modeling · 2022Article
- Molecular modeling of a series of dehydroquinate dehydratase type II inhibitors of Mycobacterium tuberculosis and design of new binders.Molecular diversity · 2021Article
- Structure-basedComputational and structural biotechnology journal · 2021Review
- Pangenome Analysis ofAntibiotics (Basel, Switzerland) · 2020Article
- Structural approaches to pathway-specific antimicrobial agents.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Synthesis and Antimycobacterial Activity of 2,5-Disubstituted and 1,2,5-Trisubstituted Benzimidazoles.Frontiers in chemistry · 2020Article
- Intrabacterial Metabolism Obscures the Successful Prediction of an InhA Inhibitor ofACS infectious diseases · 2019Article
- Mycobacterium tuberculosis serine/threonine protein kinases: structural information for the design of their specific ATP-competitive inhibitors.Journal of computer-aided molecular design · 2018Article
- Comparing and Validating Machine Learning Models for Mycobacterium tuberculosis Drug Discovery.Molecular pharmaceutics · 2018Article
- Examining the role of protein structural dynamics in drug resistance inChemical science · 2017Article
- Docking Screens for Novel Ligands Conferring New Biology.Journal of medicinal chemistry · 2016Review
- Computational protein-ligand docking and virtual drug screening with the AutoDock suite.Nature protocols · 2016Article
- 1001 Ways to run AutoDock Vina for virtual screening.Journal of computer-aided molecular design · 2016Article
- Predicting Mouse Liver Microsomal Stability with "Pruned" Machine Learning Models and Public Data.Pharmaceutical research · 2016Article
- Illustrating and homology modeling the proteins of the Zika virus.F1000Research · 2016Article
- Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase.Bioorganic & medicinal chemistry letters · 2015Article
- Charting a Path to Success in Virtual Screening.Molecules (Basel, Switzerland) · 2015Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Isoniazid (INH) is usually administered to treat latent Mycobacterium tuberculosis (Mtb) infections and is used in combination therapy to treat active tuberculosis (TB). Unfortunately, resistance to this drug is hampering its clinical effectiveness. INH is a prodrug that must be activated by Mtb catalase-peroxidase (KatG) before it can inhibit InhA (Mtb enoyl-acyl-carrier-protein reductase). Isoniazid-resistant cases of TB found in clinical settings usually involve mutations in or deletion of katG, which abrogate INH activation. Compounds that inhibit InhA without requiring prior activation by KatG would not be affected by this resistance mechanism and hence would display continued potency against these drug-resistant isolates of Mtb. Virtual screening experiments versus InhA in the GO Fight Against Malaria (GO FAM) project were designed to discover new scaffolds that display base-stacking interactions with the NAD cofactor. GO FAM experiments included targets from other pathogens, including Mtb, when they had structural similarity to a malaria target. Eight of the 16 soluble compounds identified by docking against InhA plus visual inspection were modest inhibitors and did not require prior activation by KatG. The best two inhibitors discovered are both fragment-sized compounds and displayed Ki values of 54 and 59 μM, respectively. Importantly, the novel inhibitors discovered have low structural similarity to known InhA inhibitors and thus help expand the number of chemotypes on which future medicinal chemistry efforts can be focused. These new fragment hits could eventually help advance the fight against INH-resistant Mtb strains, which pose a significant global health threat.
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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.