ReviewChemical reviews2025
Advancing Covalent Ligand and Drug Discovery beyond Cysteine.
Review in Chemical reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed.
- Chemical reactions for the ligand-directed modification of native proteins.Chemical Society reviews · 2026Review
- The evolution of click chemistry: from classical reactions to next-generation platforms.RSC advances · 2026Review
- Progress and challenges in traceless ligand-directed labelling chemistry.Communications chemistry · 2026Review
- Article
- 3-Hydroxydehydroleucodin ameliorates neuroinflammation and ischemic brain injury by blocking the TRIM21-PRDX1 interaction.Acta pharmacologica Sinica · 2026Article
- Enhancing De Novo Designed Peptides and Proteins via Irreversible Covalent Isoquinolinium Capture.ACS chemical biology · 2026Article
- SuFEx chemistry for nucleosides, nucleotides, and nucleic acids.RSC chemical biology · 2026Review
- A covalent PFKL activator suppresses tumor growth.Nature chemical biology · 2026Article
- Generation of membrane-permeable cyclic peptides inhibiting protein-protein interaction.Nature chemical biology · 2026Article
- Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles.bioRxiv : the preprint server for biology · 2026Article
- Covalent Inhibitors in Antimicrobial Drug Development-Beyond β-Lactams.Molecules (Basel, Switzerland) · 2026Review
- Mapping Functionally Relevant Tractable Lysines of Challenging Protein Targets by Covalent Fragment Screening.Chembiochem : a European journal of chemical biology · 2026Article
- A chemoproteomic atlas of the human purine interactome for regioselective ligand discovery.Nature communications · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- Development of a Lysine-Reactive Targeted Covalent Inhibitor for the P300/CBP-Associated Factor Bromodomain Through Structure-Based Design.ChemMedChem · 2026Article
- Covalent Targeting of Histidine Residues: A Ligand-First Approach.Journal of medicinal chemistry · 2026Article
- Benchmarking co-folding methods to predict the structures of covalent protein-ligand complexes.Acta pharmacologica Sinica · 2026Article
- Covalent Protein Inhibitors via Tyrosine and Tryptophan Conjugation with Cyclic Imine Mannich Electrophiles.Angewandte Chemie (International ed. in English) · 2026Article
- Protein structural dynamics in covalent drug design: insights from irreversible and reversible covalent inhibitors.RSC chemical biology · 2026Review
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Targeting intractable proteins remains a key challenge in drug discovery, as these proteins often lack well-defined binding pockets or possess shallow surfaces not readily addressed by traditional drug design. Covalent chemistry has emerged as a powerful solution for accessing protein sites in difficult to ligand regions. By leveraging activity-based protein profiling (ABPP) and LC-MS/MS technologies, academic groups and industry have identified cysteine-reactive ligands that enable selective targeting of challenging protein sites to modulate previously inaccessible biological pathways. Cysteines within a protein are rare, however, and developing covalent ligands that target additional residues hold great promise for further expanding the ligandable proteome. This review highlights recent advancements in targeting amino acids beyond cysteine binding with an emphasis on tyrosine- and lysine-directed covalent ligands and their applications in chemical biology and therapeutic development. We outline the process of developing covalent ligands using chemical proteomic methodology, highlighting recent successful examples and discuss considerations for future expansion to additional amino acid sites on proteins.
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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.