ArticleJournal of medicinal chemistry2024
Structure-Guided Design and Optimization of Covalent VHL-Targeted Sulfonyl Fluoride PROTACs.
Article in Journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Multicomponent Stapling of Glucagon-Like Peptide-1 Enables Receptor-Guided PROTAC Delivery.Angewandte Chemie (International ed. in English) · 2026Article
- Counteranion-mediated dynamic kinetic asymmetric fluorination to access sulfur-stereogenic center.Nature communications · 2026Article
- Discovery of a KLHL41 Ligand for Muscle Specific Protein Degradation.Nature communications · 2026Article
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Small-molecule degraders for oncogenic KRASNature communications · 2026Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Review
- Advancing Design Strategy of PROTACs for Cancer Therapy.MedComm · 2025Review
- Identification of Actionable Targeted Protein Degradation Effector Sites through Site-Specific Ligand Incorporation-Induced Proximity (SLIP).Journal of the American Chemical Society · 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
- Discovery of a Series of Covalent Ligands That Bind to Cys77 of the Von Hippel-Lindau Tumor Suppressor Protein (VHL).ACS medicinal chemistry letters · 2025Article
- Total syntheses of cyclohelminthol I-IV reveal a new cysteine-selective covalent reactive group.Chemical science · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Non-Markovian Dynamic Models Identify Non-Canonical KRAS-VHL Encounter Complex Conformations for Novel PROTAC Design.JACS Au · 2024Article
- Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have emerged as a therapeutic modality to induce targeted protein degradation (TPD) by harnessing cellular proteolytic degradation machinery. PROTACs which ligand the E3 ligase in a covalent manner have attracted intense interest; however, covalent PROTACs with a broad protein of interest (POI) scope have proven challenging to discover by design. Here, we report the structure-guided design and optimization of Von Hippel-Lindau (VHL) protein-targeted sulfonyl fluorides which covalently bind Ser110 in the HIF1α binding site. We demonstrate that their incorporation in bifunctional degraders induces targeted protein degradation of BRD4 or the androgen receptor without further linker optimization. Our study discloses the first covalent VHL ligands which can be implemented directly in bifunctional degrader design, expanding the substrate scope of covalent E3 ligase PROTACs.
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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.