ArticleJournal of medicinal chemistry2017
BET Bromodomain Inhibitors with One-Step Synthesis Discovered from Virtual Screen.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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
22 citing papers in PubMed.
- Macrocyclic dihydropyridine analogs as pan-BET BD2-preferred inhibitors.European journal of medicinal chemistry · 2025Article
- Differential molecular interactions between iberiotoxin and human SLO3 and SLO1 potassium channels.Journal of molecular modeling · 2025Article
- Docking‑based virtual screening of BRD4 (BD1) inhibitors: assessment of docking methods, scoring functions and in silico molecular properties.BMC chemistry · 2024Article
- Male contraception: narrative review of ongoing research.Basic and clinical andrology · 2023Review
- Recent advances in the multicomponent synthesis of heterocycles using tetronic acid.RSC advances · 2023Review
- Various gene modification techniques to discover molecular targets for nonhormonal male contraceptives: A review.International journal of reproductive biomedicine · 2023Review
- 1,4-Dihydropyridinebutyrolactone-derived ring-opened ester and amide analogs targeting BET bromodomains.Archiv der Pharmazie · 2022Article
- Dihydropyridine Lactam Analogs Targeting BET Bromodomains.ChemMedChem · 2022Article
- Update on Novel Hormonal and Nonhormonal Male Contraceptive Development.The Journal of clinical endocrinology and metabolism · 2021Review
- Computational Prediction of Chemical Tools for Identification and Validation of Synthetic Lethal Interaction Networks.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Bromodomain and BET family proteins as epigenetic targets in cancer therapy: their degradation, present drugs, and possible PROTACs.RSC advances · 2020Review
- Novel Pyrrolopyridone Bromodomain and Extra-Terminal Motif (BET) Inhibitors Effective in Endocrine-Resistant ER+ Breast Cancer with Acquired Resistance to Fulvestrant and Palbociclib.Journal of medicinal chemistry · 2020Article
- SAR by (Protein-Observed)Accounts of chemical research · 2019Review
- Systematically Mitigating the p38α Activity of Triazole-based BET Inhibitors.ACS medicinal chemistry letters · 2019Article
- BET bromodomain inhibitors: fragment-based in silico design using multi-target QSAR models.Molecular diversity · 2019Article
- Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor.Organic & biomolecular chemistry · 2019Article
- Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe.ACS medicinal chemistry letters · 2018Article
- Targeting Brd4 for cancer therapy: inhibitors and degraders.MedChemComm · 2018Review
- Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression.Journal of medicinal chemistry · 2018Article
- ICBS 2017 in Shanghai-Illuminating Life with Chemical Innovation.ACS chemical biology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors.
Funding
Abstract
Chemical inhibition of epigenetic regulatory proteins BrdT and Brd4 is emerging as a promising therapeutic strategy in contraception, cancer, and heart disease. We report an easily synthesized dihydropyridopyrimidine pan-BET inhibitor scaffold, which was uncovered via a virtual screen followed by testing in a fluorescence anisotropy assay. Dihydropyridopyimidine 3 was subjected to further characterization and is highly selective for the BET family of bromodomains. Structure-activity relationship data and ligand deconstruction highlight the importance of the substitution of the uracil moiety for potency and selectivity. Compound 3 was also cocrystallized with Brd4 for determining the ligand binding pose and rationalizing subsequent structure-activity data. An additional series of dihydropyridopyrimidines was synthesized to exploit the proximity of a channel near the ZA loop of Brd4, leading to compounds with submicromolar affinity and cellular target engagement. Given these findings, novel and easily synthesized inhibitors are being introduced to the growing field of bromodomain inhibitor development.
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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.