ArticleNature communications2023
Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- BromoCatch: a self-labelling tag platform for protein modification and live cell imaging.Nature communications · 2026Article
- Discovery of SKP2-Recruiting PROTACs for Target Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SH2Journal of medicinal chemistry · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 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
- Update on Structure and Function of SH2 Domains: Mechanisms and Emerging Targeting Strategies.International journal of molecular sciences · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Identification of Actionable Targeted Protein Degradation Effector Sites through Site-Specific Ligand Incorporation-Induced Proximity (SLIP).Journal of the American Chemical Society · 2025Article
- Loss of Socs2 improves molecular responses to IFNα in a mouse model of myeloproliferative neoplasms driven by JAK2-V617F.Leukemia · 2025Article
- Implications of frequent hitter E3 ligases in targeted protein degradation screens.Nature chemical biology · 2025Review
- Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open.RSC medicinal chemistry · 2025Article
- Leveraging Therapeutic Proteins and Peptides fromInternational journal of molecular sciences · 2024Article
- Article
- The druggability of SH2 domains unmasked.Nature chemical biology · 2024Article
- Unravelling the druggability and immunological roles of the SOCS-family proteins.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signaling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties of phosphate and its mimetics. Here, we use structure-based design to target the SH2 domain of the E3 ligase suppressor of cytokine signaling 2 (SOCS2). Starting from the highly ligand-efficient pY amino acid, a fragment growing approach reveals covalent modification of Cys111 in a co-crystal structure, which we leverage to rationally design a cysteine-directed electrophilic covalent inhibitor MN551. We report the prodrug MN714 containing a pivaloyloxymethyl (POM) protecting group and evidence its cell permeability and capping group unmasking using cellular target engagement and in-cell
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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.