ArticleCell chemical biology2021
Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 153 citations in OpenAlex.
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- Photoproximity labeling of c-Myc reveals SLK as a cancer-specific co-regulator.Nature chemical biology · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- Chemical Induction of MYC Protein Degradation via MYC-MAX Disruption and 20S Proteasome Activation.ACS chemical biology · 2026Article
- Progressive intestinal tumor cell plasticity, Myc activation, and loss of Lgr5Science advances · 2026Article
- Mild Transsulfinamidation Enables Rapid Access to Sulfinamides, Sulfonamides, and Sulfonimidamides.Organic letters · 2026Article
- No Time to Fold: Intrinsically Disordered Microproteins in Action.Biochemistry · 2026Review
- Igalan attenuates sepsis-induced inflammation through covalent targeting of the NLRP3 inflammasome pathway.RSC chemical biology · 2026Article
- A small molecule inhibitor of RNA-binding protein IGF2BP3 shows anti-leukemic activity.Haematologica · 2026Article
- Damage to newly synthesized proteins is a major cause of Cd(II) toxicity counteracted by proteasomes and integrated stress response in human cells.Chemico-biological interactions · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
- l-2-Hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression.The Journal of clinical investigation · 2026Article
- Article
- Insights into the Design of MYC-Targeting Proteolysis Targeting Chimeras (PROTACs).Molecules (Basel, Switzerland) · 2026Article
- Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy.Molecular therapy. Nucleic acids · 2026Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule.Science advances · 2026Article
- Palmitic acid activates c-Myc via dual palmitoylation-dependent pathways to promote colon cancer.Cell discovery · 2026Article
- Epithelial AhR Suppresses Allergen-Induced Oxidative Stress and Senescence via c-Myc Regulation.Antioxidants (Basel, Switzerland) · 2025Article
- FKBP9 enhances IGF2BP1-mediated mJHEP reports : innovation in hepatology · 2025Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
MYC is a major oncogenic transcriptional driver of most human cancers that has remained intractable to direct targeting because much of MYC is intrinsically disordered. Here, we have performed a cysteine-reactive covalent ligand screen to identify compounds that could disrupt the binding of MYC to its DNA consensus sequence in vitro and also impair MYC transcriptional activity in situ in cells. We have identified a covalent ligand, EN4, that targets cysteine 171 of MYC within a predicted intrinsically disordered region of the protein. We show that EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. We also show initial structure-activity relationships of EN4 and identify compounds that show improved potency. Overall, we identify a unique ligandable site within an intrinsically disordered region of MYC that leads to inhibition of MYC transcriptional activity.
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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.