ArticleJournal of medicinal chemistry2015
Structure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 103 citations in OpenAlex.
- Identification of Novel Bromodomain-Containing Protein 4 (BRD4) Binders through 3D Pharmacophore-Based Repositioning Screening Campaign.Molecules (Basel, Switzerland) · 2024Article
- Chemically induced degradation of epigenetic targets.Chemical Society reviews · 2023Review
- Streamlined DNA-encoded small molecule library screening and validation for the discovery of novel chemotypes targeting BET proteins.Molecular therapy. Nucleic acids · 2023Article
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- PROTAC'ing oncoproteins: targeted protein degradation for cancer therapy.Molecular cancer · 2023Review
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- Recent Development of Bis-Cyclometalated Chiral-at-Iridium and Rhodium Complexes for Asymmetric Catalysis.ACS organic & inorganic Au · 2022Review
- Probing GPCR Dimerization Using Peptides.Frontiers in endocrinology · 2022Review
- Discovery of Novel Tetrahydro-β-carboline Containing Aminopeptidase N Inhibitors as Cancer Chemosensitizers.Frontiers in oncology · 2022Article
- Bioactivation of Isoxazole-Containing Bromodomain and Extra-Terminal Domain (BET) Inhibitors.Metabolites · 2021Article
- Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5.Molecules (Basel, Switzerland) · 2021Article
- Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation.Beilstein journal of organic chemistry · 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
- Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction.Nature communications · 2020Article
- Bromodomains: a new target class for drug development.Nature reviews. Drug discovery · 2019Review
- 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
- Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor.Journal of medicinal chemistry · 2018Article
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Small-molecule inhibitors of bromodomain and extra terminal proteins (BET), including BRD2, BRD3, and BRD4 proteins have therapeutic potential for the treatment of human cancers and other diseases and conditions. In this paper, we report the design, synthesis, and evaluation of γ-carboline-containing compounds as a new class of small-molecule BET inhibitors. The most potent inhibitor (compound 18, RX-37) obtained from this study binds to BET bromodomain proteins (BRD2, BRD3, and BRD4) with Ki values of 3.2-24.7 nM and demonstrates high selectivity over other non-BET bromodomain-containing proteins. Compound 18 potently and selectively inhibits cell growth in human acute leukemia cell lines harboring the rearranged mixed lineage leukemia 1 gene. We have determined a cocrystal structure of 18 in complex with BRD4 BD2 at 1.4 Å resolution, which provides a solid structural basis for the compound's high binding affinity and for its further structure-based optimization. Compound 18 represents a promising lead compound for the development of a new class of therapeutics for the treatment of human cancer and other conditions.
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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.