ArticleRSC chemical biology2022
Cereblon covalent modulation through structure-based design of histidine targeting chemical probes.
Article in RSC chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Proteome-Wide Target Identification Using Reactive Metallo-Scaffolds (r-mS): A Platform for Metallodrug Discovery.Angewandte Chemie (International ed. in English) · 2026Article
- SESMic: A Reagent for the Synthesis of 5-Membered Heteroaryl Masked Sulfinates.Organic letters · 2026Article
- Covalent Targeting of Histidine Residues: A Ligand-First Approach.Journal of medicinal chemistry · 2026Article
- High-throughput discovery and characterisation of pentafluorobenzene sulfonamide modifiers of Aurora A kinase.RSC chemical biology · 2026Article
- Click chemistry-based drug delivery systems for targeted cancer therapy.Materials today. Bio · 2026Review
- A Fragment-Based Electrophile-First Approach to Target Histidine with Aryl-Fluorosulfates: Application to hMcl-1.Journal of medicinal chemistry · 2025Article
- The covalent docking software landscape: features and applications in drug design.Briefings in bioinformatics · 2025Review
- COOKIE-Pro: covalent inhibitor binding kinetics profiling on the proteome scale.Nature communications · 2025Article
- Property-Based Optimization of Cereblon-Based Molecular Glue Degraders.ACS medicinal chemistry letters · 2025Review
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- 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
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Activity-Based Protein Profiling for Functional Cysteines and Protein Target Identification.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Covalent Targeting of Histidine Residues with Aryl Fluorosulfates: Application to Mcl-1 BH3 Mimetics.Journal of medicinal chemistry · 2024Article
- Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D.Nature chemical biology · 2024Article
- Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.Journal of medicinal chemistry · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
Electrophilic biocompatible warheads, particularly cysteine-reactive acrylamides, have enabled the development of covalent inhibitor drugs and chemical biology probes, but cysteine is rarely present in protein binding sites. Therefore, expansion of the list of targetable amino acid residues is required to augment the synthetic bology toolkit of site-selective protein modifications. This work describes the first rational targeting of a specific histidine residue in a protein binding site using sulfonyl exchange chemistry. Structure-based drug design was used to incorporate sulfonyl fluoride and triazole reactive groups into the isoindolinone thalidomide congener EM12 to yield potent covalent inhibitors of the cereblon E3 ubiquitin ligase complex through engagement of His353. Conversely, the fluorosulfate derivative EM12-FS labels His353, but degrades a novel neosubstrate, the protein N-terminal glutamine amidohydrolase NTAQ1, which is involved in the N-end rule pathway and DNA damage response. Targeted protein degradation using cereblon ligands has become an important new drug discovery modality and the chemical probes and covalent labeling strategy described here will broadly impact this exciting area of therapeutic research.
Identifiers
What OpenQuestion holds
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.