Related Experiment Video
Updated: Feb 20, 2026
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor
Luiz Antonio Dutra1,2, David Heidenreich3, Gabriel Dalio Bernardes da Silva4
1School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800903, Brazil. luizdutra_qf@yahoo.com.br.
Abstract:
The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100 µM increased the melting temperature (∆Tm) of BET bromodomains by around 2.0 °C. The micromolar dissociation constant (Kd) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV Kd value accounted to 6.6 µM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains.
Insights
Resveratrol (RSV) acts as a pan-BET inhibitor, targeting epigenetic readers involved in cancer development. This study demonstrates RSV
Area of Science:
- Epigenetics
- Molecular Biology
- Pharmacology
Background:
- Resveratrol (RSV) exhibits known chemopreventive and anticancer properties.
- Epigenetic regulation, particularly through bromodomains, is crucial for controlling gene expression and tumor development.
- Bromodomains function as epigenetic readers, binding to acetylated histone tails to modulate transcription.
Purpose of the Study:
- To investigate Resveratrol's (RSV) inhibitory effects on BET bromodomains.
- To elucidate the molecular mechanisms by which RSV interacts with BET bromodomains.
Main Methods:
- Differential Scanning Fluorimetry (DSF) to assess RSV's impact on BET bromodomain thermal stability.
- Isothermal Titration Calorimetry (ITC) to quantify the binding affinity (Kd) of RSV to BRD4(1).
- Molecular docking simulations to predict the binding mode of RSV within the BRD4(1) active site.
Main Results:
- Resveratrol (RSV) demonstrated pan-BET inhibitory activity.
- DSF showed RSV increased the melting temperature (∆Tm) of BET bromodomains by approximately 2.0 °C at 100 µM.
- ITC revealed a dissociation constant (Kd) of 6.6 µM for RSV binding to BRD4(1), with molecular docking suggesting mimicry of acetyl-lysine interactions.
Conclusions:
- Resveratrol (RSV) functions as a pan-BET inhibitor, interacting with epigenetic reader domains.
- The findings support RSV's potential as a therapeutic agent targeting epigenetic mechanisms in cancer.
More Related Videos
05:33High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
Related Concept Videos
01:31Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
02:56Treatment Resistant Cancers