ArticleMedChemComm2016
Covalent Tethering of Fragments For Covalent Probe Discovery.
Article in MedChemComm, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Analysis of Covalent and Allosteric Protein Kinase Inhibitors.Molecules (Basel, Switzerland) · 2023Pooled it
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- The Current Toolbox for Covalent Inhibitors: From Hit Identification to Drug Discovery.JACS Au · 2025Review
- Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning.RSC advances · 2025Article
- Insights to Design New Drugs against Human African Trypanosomiasis Targeting Rhodesain using Covalent Docking, Molecular Dynamics Simulations, and MM-PBSA Calculations.Current computer-aided drug design · 2025Article
- Fragment-based drug discovery campaigns guided by native mass spectrometry.RSC medicinal chemistry · 2024Review
- Fragment-based drug discovery for disorders of the central nervous system: designing better drugs piece by piece.Frontiers in chemistry · 2024Review
- An electrophilic fragment screening for the development of small molecules targeting caspase-2.European journal of medicinal chemistry · 2023Article
- Docking covalent targets for drug discovery: stimulating the computer-aided drug design community of possible pitfalls and erroneous practices.Molecular diversity · 2023Review
- Technologies for Direct Detection of Covalent Protein-Drug Adducts.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Reactivity of Covalent Fragments and Their Role in Fragment Based Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Recent applications of covalent chemistries in protein-protein interaction inhibitors.RSC medicinal chemistry · 2022Review
- Covalent Fragment Screening Identifies Rgl2 RalGEF Cysteine for Targeted Covalent Inhibition of Ral GTPase Activation.ChemMedChem · 2022Article
- A direct-to-biology high-throughput chemistry approach to reactive fragment screening.Chemical science · 2021Article
- Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins.NPJ Parkinson's disease · 2021Review
- Fragment-based covalent ligand discovery.RSC chemical biology · 2021Review
- 10 years into the resurgence of covalent drugs.Future medicinal chemistry · 2021Article
- Multiparameter Kinetic Analysis for Covalent Fragment Optimization by Using Quantitative Irreversible Tethering (qIT).Chembiochem : a European journal of chemical biology · 2020Article
- Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites.ACS chemical biology · 2020Article
- Design and characterization of a heterocyclic electrophilic fragment library for the discovery of cysteine-targeted covalent inhibitors.MedChemComm · 2019Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Covalent probes and drugs have found widespread use as research tools and clinical agents. Covalent probes are useful because of their increased intracellular potency and because covalent labeling of cellular proteins can be tracked using click chemistry. Covalent drugs, on the other hand, can overcome drug resistance toward their reversible counterparts. The discovery of covalent probes and drugs usually follows two trajectories: covalent natural products and their analogues are used directly as covalent probes or drugs; or alternatively, a non-covalent probe is equipped with a reactive group and converted into a covalent probe. In both cases, there is a need to either have a natural product or a potent non-covalent scaffold. The alternative approach to discover covalent probes is to start with a drug-like fragment that already has an electrophile, and then grow the fragment into a potent lead compound. In this approach, the electrophilic fragment will react covalently with the target protein, and therefore the initial weak binding of the fragment can be amplified over time and detected using mass spectrometry. With this approach the surface of the protein can be interrogated with a library of covalent fragments to identify covalent drug binding sites. One challenge with this approach is the danger of non-specific covalent labeling of proteins with covalent fragments. The second challenge is the risk of selecting the most reactive fragment rather than the best binder if the covalent fragments are screened in mixtures. This review will highlight how covalent tethering was developed, its current state, and its future.
Identifiers
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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.