ArticleJournal of medicinal chemistry2021
Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Palbociclib targets β-catenin for degradation and synergizes with KRAS or ERK5 inhibition in colorectal cancer preclinical models.Journal of translational medicine · 2026Article
- Structural Basis for BD1-Preferring 2,4-Disubstituted Pyrimidine BRDT Inhibitors.Journal of medicinal chemistry · 2026Article
- The novel synthesis of a condensed triazineRSC advances · 2025Article
- Macrocyclic dihydropyridine analogs as pan-BET BD2-preferred inhibitors.European journal of medicinal chemistry · 2025Article
- Differential scanning fluorimetry followed by microscale thermophoresis and/or isothermal titration calorimetry as an efficient tool for ligand screening.Biophysical reviews · 2025Review
- Non-kinase off-target inhibitory activities of clinically-relevant kinase inhibitors.European journal of medicinal chemistry · 2024Review
- Identification of Novel Bromodomain-Containing Protein 4 (BRD4) Binders through 3D Pharmacophore-Based Repositioning Screening Campaign.Molecules (Basel, Switzerland) · 2024Article
- Binding Mechanism of Inhibitors to BRD4 and BRD9 Decoded by Multiple Independent Molecular Dynamics Simulations and Deep Learning.Molecules (Basel, Switzerland) · 2024Article
- Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- 1,4-Dihydropyridinebutyrolactone-derived ring-opened ester and amide analogs targeting BET bromodomains.Archiv der Pharmazie · 2022Article
- Bivalent BET Bromodomain Inhibitors Confer Increased Potency and Selectivity for BRDT via Protein Conformational Plasticity.Journal of medicinal chemistry · 2022Article
- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
BRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially.
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Registered trials
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