ArticleJournal of medicinal chemistry2012
Discovery of a novel and potent class of F. tularensis enoyl-reductase (FabI) inhibitors by molecular shape and electrostatic matching.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 67 citations in OpenAlex.
- Underexplored Ligand-Binding Features of FabI From Staphylococcus aureus and Escherichia coli: A Comparative Pharmacophoric Modeling and Surface Mapping Approach.ChemMedChem · 2026Article
- Inhibitors of the FASII Metabolic Pathway inMicroorganisms · 2026Review
- Predicting phase-I metabolism of piceatannol: an in silico study.In silico pharmacology · 2024Article
- Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay.Journal of computer-aided molecular design · 2020Article
- Structural approaches to pathway-specific antimicrobial agents.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Ligand- and Structure-Based Approaches of Escherichia coli FabI Inhibition by Triclosan Derivatives: From Chemical Similarity to Protein Dynamics Influence.ChemMedChem · 2019Article
- Shape similarity guided pose prediction: lessons from D3R Grand Challenge 3.Journal of computer-aided molecular design · 2019Article
- Determination of absolute configuration and binding efficacy of benzimidazole-based FabI inhibitors through the support of electronic circular dichroism and MM-GBSA techniques.Bioorganic & medicinal chemistry letters · 2018Article
- Advances in the Development of Shape Similarity Methods and Their Application in Drug Discovery.Frontiers in chemistry · 2018Review
- Article
- Benzimidazole-Based FabI Inhibitors: A Promising Novel Scaffold for Anti-staphylococcal Drug Development.ACS infectious diseases · 2017Article
- Drugs in development for toxoplasmosis: advances, challenges, and current status.Drug design, development and therapy · 2017Review
- Discovery of Mycobacterium tuberculosis InhA Inhibitors by Binding Sites Comparison and Ligands Prediction.Journal of medicinal chemistry · 2016Article
- Prospective evaluation of shape similarity based pose prediction method in D3R Grand Challenge 2015.Journal of computer-aided molecular design · 2016Article
- Article
- An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.Molecules (Basel, Switzerland) · 2016Article
- A pose prediction approach based on ligand 3D shape similarity.Journal of computer-aided molecular design · 2016Article
- Evaluating thermodynamic integration performance of the new amber molecular dynamics package and assess potential halogen bonds of enoyl-ACP reductase (FabI) benzimidazole inhibitors.Journal of computational chemistry · 2016Article
- Comparison of radii sets, entropy, QM methods, and sampling on MM-PBSA, MM-GBSA, and QM/MM-GBSA ligand binding energies of F. tularensis enoyl-ACP reductase (FabI).Journal of computational chemistry · 2015Article
- Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI).Bioorganic & medicinal chemistry letters · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Enoyl-acyl carrier protein (ACP) reductase, FabI, is a key enzyme in the bacterial fatty acid biosynthesis pathway (FAS II). FabI is an NADH-dependent oxidoreductase that acts to reduce enoyl-ACP substrates in a final step of the pathway. The absence of this enzyme in humans makes it an attractive target for the development of new antibacterial agents. FabI is known to be unresponsive to structure-based design efforts due to a high degree of induced fit and a mobile flexible loop encompassing the active site. Here we discuss the development, validation, and careful application of a ligand-based virtual screen used for the identification of novel inhibitors of the Francisella tularensis FabI target. In this study, four known classes of FabI inhibitors were used as templates for virtual screens that involved molecular shape and electrostatic matching. The program ROCS was used to search a high-throughput screening library for compounds that matched any of the four molecular shape queries. Matching compounds were further refined using the program EON, which compares and scores compounds by matching electrostatic properties. Using these techniques, 50 compounds were selected, ordered, and tested. The tested compounds possessed novel chemical scaffolds when compared to the input query compounds. Several hits with low micromolar activity were identified and follow-up scaffold-based searches resulted in the identification of a lead series with submicromolar enzyme inhibition, high ligand efficiency, and a novel scaffold. Additionally, one of the most active compounds showed promising whole-cell antibacterial activity against several Gram-positive and Gram-negative species, including the target pathogen. The results of a preliminary structure-activity relationship analysis are presented.
Indexed as
Identifiers
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.