ArticleScientific reports2015
Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
25 citing papers in PubMed, 64 citations in OpenAlex.
- Recent Progress and Prospect in Studying Selective Inhibitors Toward Bromodomain Family Members.Molecules (Basel, Switzerland) · 2026Review
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Modeling and Interpretability Study of the Structure-Activity Relationship for Multigeneration EGFR Inhibitors.ACS omega · 2025Article
- RAPID resistance to BET inhibitors is mediated by FGFR1 in glioblastoma.Scientific reports · 2024Article
- Kinome-Wide Virtual Screening by Multi-Task Deep Learning.International journal of molecular sciences · 2024Article
- AI-Assisted chemical probe discovery for the understudied Calcium-Calmodulin Dependent Kinase, PNCK.PLoS computational biology · 2023Article
- Structural insights into conformational stability and binding of thiazolo-[2,3-b] quinazolinone derivatives with EGFR-TKD andSaudi journal of biological sciences · 2022Article
- Emerging Promise of Computational Techniques in Anti-Cancer Research: At a Glance.Bioengineering (Basel, Switzerland) · 2022Review
- Article
- Dual-target inhibitors of bromodomain and extra-terminal proteins in cancer: A review from medicinal chemistry perspectives.Medicinal research reviews · 2022Review
- The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion.Scientific reports · 2021Article
- Systemic Analysis of the DNA Replication Regulator MCM Complex in Ovarian Cancer and Its Prognostic Value.Frontiers in oncology · 2021Article
- Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein-protein interactions.Nature communications · 2020Article
- Enhanced JunD/RSK3 signalling due to loss of BRD4/FOXD3/miR-548d-3p axis determines BET inhibition resistance.Nature communications · 2020Article
- Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan-cancer analysis.Cancer communications (London, England) · 2020Article
- Bromodomains: a new target class for drug development.Nature reviews. Drug discovery · 2019Review
- Enabling the hypothesis-driven prioritization of ligand candidates in big databases: Screenlamp and its application to GPCR inhibitor discovery for invasive species control.Journal of computer-aided molecular design · 2018Article
- Targeting bromodomain and extraterminal proteins in breast cancer.Pharmacological research · 2018Review
- Computer-Aided Drug Design in Epigenetics.Frontiers in chemistry · 2018Review
- Drug Repositioning in Glioblastoma: A Pathway Perspective.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Inhibition of cancer-promoting kinases is an established therapeutic strategy for the treatment of many cancers, although resistance to kinase inhibitors is common. One way to overcome resistance is to target orthogonal cancer-promoting pathways. Bromo and Extra-Terminal (BET) domain proteins, which belong to the family of epigenetic readers, have recently emerged as promising therapeutic targets in multiple cancers. The development of multitarget drugs that inhibit kinase and BET proteins therefore may be a promising strategy to overcome tumor resistance and prolong therapeutic efficacy in the clinic. We developed a general computational screening approach to identify novel dual kinase/bromodomain inhibitors from millions of commercially available small molecules. Our method integrated machine learning using big datasets of kinase inhibitors and structure-based drug design. Here we describe the computational methodology, including validation and characterization of our models and their application and integration into a scalable virtual screening pipeline. We screened over 6 million commercially available compounds and selected 24 for testing in BRD4 and EGFR biochemical assays. We identified several novel BRD4 inhibitors, among them a first in class dual EGFR-BRD4 inhibitor. Our studies suggest that this computational screening approach may be broadly applicable for identifying dual kinase/BET inhibitors with potential for treating various cancers.
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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.