ArticleCell chemical biology2022
Exploring the target scope of KEAP1 E3 ligase-based PROTACs.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 83 citations in OpenAlex.
- A pharmacological modality to sequester homomeric proteins.Nature chemical biology · 2026Article
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.Journal of medicinal chemistry · 2026Article
- Keap1-Kelch-targeting protein-protein interaction inhibitors, but not reversibly-binding electrophiles, increase the thermostability of Keap1 in the cellular environment.RSC chemical biology · 2026Article
- Identification of KLHL12 Ligands Using Fragment-Based Methods.Journal of medicinal chemistry · 2026Article
- Combinatorial use of VHL and KEAP1 PROTACs reveals unexpected synergy and hook effect relief.Genes & development · 2026Article
- HSP70 Interactome-Mediated Proteolysis Targeting Chimera (HSP70-PROTAC) for Ferroptosis-Driven Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Scaffolding-dependent CASP1 constrains excessive cell-intrinsic inflammatory signaling in leukemia.Cell chemical biology · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Innovative Therapies for Oncogenic KRAS Mutations: Precision Strategies with PROTACs in Cancer Treatment.Anti-cancer agents in medicinal chemistry · 2026Review
- Mode of action of a DCAF16-recruiting targeted glue that can selectively degrade BRD9.Nature communications · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12.Cell reports · 2025Article
- The Role of Reactive Oxygen Species in Lung Cancer Development: Nanomedicine as a Therapeutic Strategy.Biomolecules · 2025Review
- Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.Acta pharmaceutica Sinica. B · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Article
- Workflow for E3 Ligase Ligand Validation for PROTAC Development.ACS chemical biology · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Targeted protein degradation (TPD) uses small molecules to recruit E3 ubiquitin ligases into the proximity of proteins of interest, inducing ubiquitination-dependent degradation. A major bottleneck in the TPD field is the lack of accessible E3 ligase ligands for developing degraders. To expand the E3 ligase toolbox, we sought to convert the Kelch-like ECH-associated protein 1 (KEAP1) inhibitor KI696 into a recruitment handle for several targets. While we were able to generate KEAP1-recruiting degraders of BET family and murine focal adhesion kinase (FAK), we discovered that the target scope of KEAP1 was narrow, as targets easily degraded using a cereblon (CRBN)-recruiting degrader were refractory to KEAP1-mediated degradation. Linking the KEAP1-binding ligand to a CRBN-binding ligand resulted in a molecule that induced degradation of KEAP1 but not CRBN. In sum, we characterize tool compounds to explore KEAP1-mediated ubiquitination and delineate the challenges of exploiting new E3 ligases for generating bivalent degraders.
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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.