ArticleAngewandte Chemie (International ed. in English)2018
High-Throughput Kinetic Analysis for Target-Directed Covalent Ligand Discovery.
Article in Angewandte Chemie (International ed. in English), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- A FRET-Based Assay for Assessing Covalent Warhead Reactivity.ACS omega · 2026Article
- Normalizing Covalent Potency for Electrophilicity with Ligand Reactivity Efficiency.Journal of medicinal chemistry · 2026Review
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- The covalent docking software landscape: features and applications in drug design.Briefings in bioinformatics · 2025Review
- Covalent Ligand Electrophiles Are Differentially Activated by Proximity Effects Which Govern Latent Protein Reactivity.ACS central science · 2025Article
- COOKIE-Pro: covalent inhibitor binding kinetics profiling on the proteome scale.Nature communications · 2025Article
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- CDK2 Allosteric Modulators: The New Route in the Design of New Drugs as Anticancer and Non-hormonal Contraceptives.Current medicinal chemistry · 2025Review
- Docking covalent targets for drug discovery: stimulating the computer-aided drug design community of possible pitfalls and erroneous practices.Molecular diversity · 2023Review
- Emerging approaches to CDK inhibitor development, a structural perspective.RSC chemical biology · 2023Article
- Reactivity of Covalent Fragments and Their Role in Fragment Based Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 71 3C and SARS-CoV-2 main protease.Acta pharmaceutica Sinica. B · 2022Article
- In silico screening-based discovery of novel covalent inhibitors of the SARS-CoV-2 3CL protease.European journal of medicinal chemistry · 2022Article
- Identification of the first structurally validated covalent ligands of the small GTPase RAB27A.RSC medicinal chemistry · 2022Article
- An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 MCell chemical biology · 2021Article
- Exploring ligand binding pathways on proteins using hypersound-accelerated molecular dynamics.Nature communications · 2021Article
- Functionalized Scout Fragments for Site-Specific Covalent Ligand Discovery and Optimization.ACS central science · 2021Article
- Fragment-based covalent ligand discovery.RSC chemical biology · 2021Review
- Multicomponent reaction-derived covalent inhibitor space.Science advances · 2021Article
- Reaction screening in multiwell plates: high-throughput optimization of a Buchwald-Hartwig amination.Nature protocols · 2021Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cysteine-reactive small molecules are used as chemical probes of biological systems and as medicines. Identifying high-quality covalent ligands requires comprehensive kinetic analysis to distinguish selective binders from pan-reactive compounds. Quantitative irreversible tethering (qIT), a general method for screening cysteine-reactive small molecules based upon the maximization of kinetic selectivity, is described. This method was applied prospectively to discover covalent fragments that target the clinically important cell cycle regulator Cdk2. Crystal structures of the inhibitor complexes validate the approach and guide further optimization. The power of this technique is highlighted by the identification of a Cdk2-selective allosteric (type IV) kinase inhibitor whose novel mode-of-action could be exploited therapeutically.
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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.