ArticleOrganic & biomolecular chemistry2016
A fragment merging approach towards the development of small molecule inhibitors of Mycobacterium tuberculosis EthR for use as ethionamide boosters.
Article in Organic & biomolecular chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 48 citations in OpenAlex.
- Multi-Target Neuroprotective Compound Exhibits EAAT2-Modulating and Alzheimer's Pathology-Attenuating Effects in In Vitro and In Vivo Models.ACS chemical neuroscience · 2026Article
- Augmenting the Anti-Leukemic Activity of the BCL-2 Inhibitor Venetoclax Through Its Transformation Into Polypharmacologic Dual BCL-2/HDAC1 and Dual BCL-2/HDAC6 Inhibitors.Drug development research · 2025Article
- Fragmenstein: predicting protein-ligand structures of compounds derived from known crystallographic fragment hits using a strict conserved-binding-based methodology.Journal of cheminformatics · 2025Article
- Fragment Merging Using a Graph Database Samples Different Catalogue Space than Similarity Search.Journal of chemical information and modeling · 2023Article
- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Phosphatidylcholine (18:0/20:4), a potential biomarker to predict ethionamide-induced hepatic steatosis in rats.Journal of applied toxicology : JAT · 2022Article
- Cosolvent Simulations with Fragment-Bound Proteins Identify Hot Spots to Direct Lead Growth.Journal of chemical theory and computation · 2022Article
- Using Structure-guided Fragment-Based Drug Discovery to TargetFrontiers in molecular biosciences · 2022Review
- Demonstration of the utility of DOS-derived fragment libraries for rapid hit derivatisation in a multidirectional fashion.Chemical science · 2020Article
- Review
- Relative Binding Energies Predict Crystallographic Binding Modes of Ethionamide Booster Lead Compounds.The journal of physical chemistry letters · 2019Article
- Using Fragment-Based Approaches to Discover New Antibiotics.SLAS discovery : advancing life sciences R & D · 2018Article
- NMR-Fragment Based Virtual Screening: A Brief Overview.Molecules (Basel, Switzerland) · 2018Review
- Article
- Review
- Fragment-Sized EthR Inhibitors Exhibit Exceptionally Strong Ethionamide Boosting Effect in Whole-Cell Mycobacterium tuberculosis Assays.ACS chemical biology · 2017Article
- Target Identification ofFrontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
With the ever-increasing instances of resistance to frontline TB drugs there is the need to develop novel strategies to fight the worldwide TB epidemic. Boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial transcriptional repressor protein EthR is an attractive therapeutic strategy. Herein we report the use of a fragment based drug discovery approach for the structure-guided systematic merging of two fragment molecules, each binding twice to the hydrophobic cavity of EthR from M. tuberculosis. These together fill the entire binding pocket of EthR. We elaborated these fragment hits and developed small molecule inhibitors which have a 100-fold improvement of potency in vitro over the initial fragments.
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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.