ArticleNature chemical biology2020
Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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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
95 citing papers in PubMed, 207 citations in OpenAlex.
- Trial
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Assessing the Stability of Molecular Glues with Weighted Ensemble Simulations.Journal of chemical theory and computation · 2026Article
- Ubiquitin family as novel protein partners for molecular glues.npj drug discovery · 2026Review
- Study protocol for a phase I investigator-initiated clinical trial of E7820 in Japanese patients with unresectable solid tumours: CIRCUS trial (NCCH2303).Japanese journal of clinical oncology · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Localized heme sensing through a ternary molecular glue.bioRxiv : the preprint server for biology · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026Review
- Hydrophobic tagging: A promising paradigm for targeted protein degradation.Cell insight · 2026Review
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- Clues for glues: from serendipity to nature's blueprints in degrader discovery.Essays in biochemistry · 2025Review
- RNA-binding proteins as therapeutic targets in cancer.RNA biology · 2025Review
- Article
- Mutation of CMTR2 in Lung Adenocarcinoma Alters RNA Alternative Splicing and Reveals Therapeutic Vulnerabilities.Nature communications · 2025Article
- A small-molecule VHL molecular glue degrader for cysteine dioxygenase 1.Nature chemical biology · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms.Chinese herbal medicines · 2025Review
- RNA-binding motif protein RBM39 enhances the proliferation of gastric cancer cells by facilitating an oncogenic splicing switch in MRPL33.Acta pharmacologica Sinica · 2025Article
- Discovery of a molecular glue for EGFR degradation.Oncogene · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The investigational drugs E7820, indisulam and tasisulam (aryl-sulfonamides) promote the degradation of the splicing factor RBM39 in a proteasome-dependent mechanism. While the activity critically depends on the cullin RING ligase substrate receptor DCAF15, the molecular details remain elusive. Here we present the cryo-EM structure of the DDB1-DCAF15-DDA1 core ligase complex bound to RBM39 and E7820 at a resolution of 4.4 Å, together with crystal structures of engineered subcomplexes. We show that DCAF15 adopts a new fold stabilized by DDA1, and that extensive protein-protein contacts between the ligase and substrate mitigate low affinity interactions between aryl-sulfonamides and DCAF15. Our data demonstrate how aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively bind and degrade RBM39 and the closely related splicing factor RBM23 without the requirement for a high-affinity ligand, which has broad implications for the de novo discovery of molecular glue degraders.
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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.