ArticleRSC medicinal chemistry2022
Covalent drugs targeting histidine - an unexploited opportunity?
Article in RSC medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed.
- SuFEx chemistry for nucleosides, nucleotides, and nucleic acids.RSC chemical biology · 2026Review
- Covalent Targeting of Histidine Residues: A Ligand-First Approach.Journal of medicinal chemistry · 2026Article
- Profiling the proteome-wide selectivity of diverse electrophiles.Nature chemistry · 2025Article
- Histidine Focused Covalent Inhibitors Targeting Acetylcholinesterase: A Computational Pipeline for Multisite Therapeutic Discovery in Alzheimer's Disease.ACS chemical neuroscience · 2025Article
- Advances in sulfonyl exchange chemical biology: expanding druggable target space.Chemical science · 2025Review
- Proximity-induced SuFEx increases the potency of cytosolic nucleotidase inhibitors and reveals a rare example of covalently targeted histidine.RSC chemical biology · 2025Article
- Identification of an Allene Warhead That Selectively Targets a Histidine Residue in theACS medicinal chemistry letters · 2025Article
- Article
- Covalent Targeting of Histidine Residues with Aryl Fluorosulfates: Application to Mcl-1 BH3 Mimetics.Journal of medicinal chemistry · 2024Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Covalent Inhibition of a Host-Pathogen Protein-Protein Interaction Reduces the Infectivity ofJACS Au · 2024Article
- Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.Journal of medicinal chemistry · 2024Article
- Peptide-Based Covalent Inhibitors Bearing Mild Electrophiles to Target a Conserved His Residue of the Bacterial Sliding Clamp.JACS Au · 2024Article
- Development of sulfonyl fluoride chemical probes to advance the discovery of cereblon modulators.RSC medicinal chemistry · 2024Article
- Covalent Stapling of the Cereblon Sensor Loop Histidine Using Sulfur-Heterocycle Exchange.ACS medicinal chemistry letters · 2023Article
- Development of a covalent cereblon-based PROTAC employing a fluorosulfate warhead.RSC chemical biology · 2023Article
- Efficient Ligand Discovery Using Sulfur(VI) Fluoride Reactive Fragments.ACS chemical biology · 2023Article
- Activation-Free Sulfonyl Fluoride Probes for Fragment Screening.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Covalent drugs and chemical probes often possess pharmacological advantages over reversible binding ligands, such as enhanced potency and pharmacodynamic duration. The highly nucleophilic cysteine thiol is commonly targeted using acrylamide electrophiles, but the amino acid is rarely present in protein binding sites. Sulfonyl exchange chemistry has expanded the covalent drug discovery toolkit by enabling the rational design of irreversible inhibitors targeting tyrosine, lysine, serine and threonine. Probes containing the sulfonyl fluoride warhead have also been shown to serendipitously label histidine residues in proteins. Histidine targeting is an attractive prospect because the residue is frequently proximal to protein small molecule ligands and the imidazole side chain possesses desirable nucleophilicity. We recently reported the design of cereblon molecular glues to site-selectively modify a histidine in the thalidomide binding site using sulfonyl exchange chemistry. We believe that histidine targeting holds great promise for future covalent drug development and this Opinion highlights these opportunities.
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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.