ArticleNature chemical biology2016
Design and characterization of bivalent BET inhibitors.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed.
- A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly.ACS central science · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026Article
- The Selective Bromodomain and Extra-Terminal Domain (BET) Inhibitor RVX-208 Reduces Cocaine-Seeking Behaviour and Alters Proteomic Pathways in the Nucleus Accumbens.Addiction biology · 2026Article
- Photodynamic enhancement of PROTAC prodrug activation in hypoxic tumors.Acta pharmaceutica Sinica. B · 2025Article
- [Design, Synthesis, and Efficacy Evaluation of a Novel BRD4/HDAC Dual-Target Small-Molecule Inhibitor in Prostate Cancer].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Epigenetic Dysregulation in Cancer: Implications for Gene Expression and DNA Repair-Associated Pathways.International journal of molecular sciences · 2025Review
- Advancing Design Strategy of PROTACs for Cancer Therapy.MedComm · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- SynBioNanoDesign: pioneering targeted drug delivery with engineered nanomaterials.Journal of nanobiotechnology · 2025Review
- A "Goldilocks Zone" for Recruiting BET Proteins with Bromodomain-1-Selective Ligands.ACS chemical biology · 2024Article
- Novel PROTAC probes targeting FOSL1 degradation to eliminate head and neck squamous cell carcinoma cancer stem cells.Bioorganic chemistry · 2024Article
- An updated patent review of BRD4 degraders.Expert opinion on therapeutic patents · 2024Review
- Identification of Novel Bromodomain-Containing Protein 4 (BRD4) Binders through 3D Pharmacophore-Based Repositioning Screening Campaign.Molecules (Basel, Switzerland) · 2024Article
- Article
- Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.Communications chemistry · 2024Article
- PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.Current topics in medicinal chemistry · 2024Review
- Facile Synthesis of Homodimeric Protein Ligands.Chembiochem : a European journal of chemical biology · 2023Article
- Design and Characterization of 1,3-Dihydro-2ACS medicinal chemistry letters · 2023Article
23 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
Cellular signaling is often propagated by multivalent interactions. Multivalency creates avidity, allowing stable biophysical recognition. Multivalency is an attractive strategy for achieving potent binding to protein targets, as the affinity of bivalent ligands is often greater than the sum of monovalent affinities. The bromodomain and extraterminal domain (BET) family of transcriptional coactivators features tandem bromodomains through which BET proteins bind acetylated histones and transcription factors. All reported antagonists of the BET protein BRD4 bind in a monovalent fashion. Here we describe, to our knowledge for the first time, a bivalent BET bromodomain inhibitor-MT1-which has unprecedented potency. Biophysical and biochemical studies suggest MT1 is an intramolecular bivalent BRD4 binder that is more than 100-fold more potent, in cellular assays, than the corresponding monovalent antagonist, JQ1. MT1 significantly (P < 0.05) delayed leukemia progression in mice, as compared to JQ1. These data qualify a powerful chemical probe for BET bromodomains and a rationale for further development of multidomain inhibitors of epigenetic reader proteins.
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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.