ArticleJournal of medicinal chemistry2019
Designing Dual Inhibitors of Anaplastic Lymphoma Kinase (ALK) and Bromodomain-4 (BRD4) by Tuning Kinase Selectivity.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 64 citations in OpenAlex.
- Consensus Pharmacological Interactions for PLK2 Inhibitor Identification in Colorectal Cancer Treatment.Journal of chemical information and modeling · 2026Article
- Therapeutic Targeting of BET Proteins in Sarcoma.Molecular cancer therapeutics · 2025Review
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Identification of Novel Bromodomain-Containing Protein 4 (BRD4) Binders through 3D Pharmacophore-Based Repositioning Screening Campaign.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
- Bromodomain inhibitors and therapeutic applications.Current opinion in chemical biology · 2023Review
- The era of high-quality chemical probes.RSC medicinal chemistry · 2022Article
- Dual-target inhibitors of bromodomain and extra-terminal proteins in cancer: A review from medicinal chemistry perspectives.Medicinal research reviews · 2022Review
- New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology.Frontiers in immunology · 2022Review
- Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.Journal of medicinal chemistry · 2021Article
- Pursuing Precision: Receptor Tyrosine Kinase Inhibitors for Treatment of Pediatric Solid Tumors.Cancers · 2021Review
- LigTMap: ligand and structure-based target identification and activity prediction for small molecular compounds.Journal of cheminformatics · 2021Article
- Polymer-Supported Synthesis of Various Pteridinones and Pyrimidodiazepinones.Molecules (Basel, Switzerland) · 2021Article
- Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.Journal of medicinal chemistry · 2021Review
- Design, synthesis, and biological evaluation of quinazolin-4(3Acta pharmaceutica Sinica. B · 2021Article
- Design of thienopyranone-based BET inhibitors that bind multiple synthetic lethality targets.Scientific reports · 2020Article
- Small-Molecule Dual PLK1 and BRD4 Inhibitors are Active Against Preclinical Models of Pediatric Solid Tumors.Translational oncology · 2020Article
- Systematically Mitigating the p38α Activity of Triazole-based BET Inhibitors.ACS medicinal chemistry letters · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Concomitant inhibition of anaplastic lymphoma kinase (ALK) and bromodomain-4 (BRD4) is a potential therapeutic strategy for targeting two key oncogenic drivers that co-segregate in a significant fraction of high-risk neuroblastoma patients, mutation of ALK and amplification of MYCN. Starting from known dual polo-like kinase (PLK)-1-BRD4 inhibitor BI-2536, we employed structure-based design to redesign this series toward compounds with a dual ALK-BRD4 profile. These efforts led to compound ( R)-2-((2-ethoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-7-ethyl-5-methyl-8-((4-methylthiophen-2-yl)methyl)-7,8-dihydropteridin-6(5 H)-one (16k) demonstrating improved ALK activity and significantly reduced PLK-1 activity, while maintaining BRD4 activity and overall kinome selectivity. We demonstrate the compounds' on-target engagement with ALK and BRD4 in cells as well as favorable broad kinase and bromodomain selectivity.
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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.