ArticleJournal of the American Chemical Society2024
Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders.
Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 36 citations in OpenAlex.
- A Perspective on Covalent Hit Identification and Validation in the European Pharmaceutical Industry.Chembiochem : a European journal of chemical biology · 2026Article
- Proteome-Wide Target Identification Using Reactive Metallo-Scaffolds (r-mS): A Platform for Metallodrug Discovery.Angewandte Chemie (International ed. in English) · 2026Article
- Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles.bioRxiv : the preprint server for biology · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5.Nature chemical biology · 2026Article
- Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 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
- IRAK4 Regulates NF-κB signaling to suppress CD8 + T cell activity and promote immune evasion in glioblastoma development.Cancer immunology, immunotherapy : CII · 2026Article
- Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC.Angewandte Chemie (International ed. in English) · 2025Article
- Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone Complex.bioRxiv : the preprint server for biology · 2025Article
- COOKIE-Pro: covalent inhibitor binding kinetics profiling on the proteome scale.Nature communications · 2025Article
- CySP3-96 Enables Scalable, Streamlined, and Low-Cost Sample Preparation for Cysteine Chemoproteomic Applications.Molecular & cellular proteomics : MCP · 2025Article
- Gas Phase Separation of Modified Peptides for Activity-Based Protein Profiling.Analytical chemistry · 2025Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Enantiocontrolled Azetidine Library Synthesis via Strain-Release Functionalization of 1-Azabicyclobutanes.Journal of the American Chemical Society · 2025Article
- A Guide to Extrachromosomal DNA: Cancer's Dynamic Circular Genome.Cancer discovery · 2025Review
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.Journal of the American Chemical Society · 2025Article
- Review
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Covalent chemistry coupled with activity-based protein profiling (ABPP) offers a versatile way to discover ligands for proteins in native biological systems. Here, we describe a set of stereo- and regiochemically defined spirocycle acrylamides and the analysis of these electrophilic "stereoprobes" in human cancer cells by cysteine-directed ABPP. Despite showing attenuated reactivity compared to structurally related azetidine acrylamide stereoprobes, the spirocycle acrylamides preferentially liganded specific cysteines on diverse protein classes. One compound termed ZL-12A promoted the degradation of the TFIIH helicase ERCC3. Interestingly, ZL-12A reacts with the same cysteine (C342) in ERCC3 as the natural product triptolide, which did not lead to ERCC3 degradation but instead causes collateral loss of RNA polymerases. ZL-12A and triptolide cross-antagonized one another's protein degradation profiles. Finally, we provide evidence that the antihypertension drug spironolactone─previously found to promote ERCC3 degradation through an enigmatic mechanism─also reacts with ERCC3_C342. Our findings thus describe monofunctional degraders of ERCC3 and highlight how covalent ligands targeting the same cysteine can produce strikingly different functional outcomes.
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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.