ArticleScientific reports2017
Selective inhibition mechanism of RVX-208 to the second bromodomain of bromo and extraterminal proteins: insight from microsecond molecular dynamics simulations.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed.
- Fragment-Based Discovery of BRD4-BD2 Selective Binders: Biophysical Validation and Structural Insights for Domain-Selective Inhibitor Design.ACS omega · 2026Article
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Editorial: Natural compounds regulating epigenetics for treating chronic inflammatory diseases.Frontiers in pharmacology · 2022Article
- The conformational stability of pro-apoptotic BAX is dictated by discrete residues of the protein core.Nature communications · 2021Article
- Discovery of a hidden transient state in all bromodomain families.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes.Clinical epigenetics · 2020Article
- Investigating Phosphorylation-Induced Conformational Changes in WNK1 Kinase by Molecular Dynamics Simulations.ACS omega · 2019Article
- Next Generation Techniques for Determination of Protein-Protein Interactions: Beyond the Crystal Structure.Current pathobiology reports · 2019Article
- Proteomics for cancer drug design.Expert review of proteomics · 2019Article
- Identification of a Novel Protein Arginine Methyltransferase 5 Inhibitor in Non-small Cell Lung Cancer by Structure-Based Virtual Screening.Frontiers in pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RVX-208 is a recently reported inhibitor of bromo and extraterminal (BET) family proteins (including BRD2-4 and BRDT) with selectivity for the second bromodomain (BD2), currently in phase III clinical trials. Despite of its promising antitumor activity, due to the conserved folds of the first and second bromodomains (BD1 and BD2), the detailed selectivity mechanism of RVX-208 towards BD2 over BD1 is still unknown. To elucidate selective inhibition mechanism of RVX-208 to BD2, microsecond molecular dynamics simulations were performed in this study for BRD2-BD1, BRD2-BD2 and BRD4-BD1 with and without RVX-208, respectively. Binding free energy calculations show that there exists strongest interaction between RVX-208 and BRD2-BD2. Leu383 and Asn429 are two most important residues of BRD2-BD2 for binding to RVX-208. Structural network analysis reveals that RVX-208 can shorten the communication path of ZA and BC loops in BRD2-BD2 pocket, making pocket more suitable to accommodate RVX-208. Additionally, different behaviors of His433 (Asp160 in BRD2-BD1) and Val435 (Ile162 in BRD2-BD1) in BRD2-BD2 are key factors responsible for selective binding of RVX-208 to BRD2-BD2. The proposed selective inhibition mechanism of RVX-208 to BRD2-BD2 can be helpful for rational design of novel selective inhibitors of the second bromodomain of BET family proteins.
Indexed as
Identifiers
What OpenQuestion holds
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.