Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mechanistic basis for selective Csm6-2 activation by cyclic penta-adenylate in a type III CRISPR-Cas system.

The EMBO journal·2026
Same author

Molecular basis of oocyte cytoplasmic lattice assembly.

Nature·2026
Same author

A Meier-Gorlin syndrome mutation impairs the loading of the MCM2-7 complex during DNA replication initiation.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Aneuploidy of chromosome 8 promotes the mesenchymal lineage during cell fate transitions.

Science advances·2026
Same author

Neuroimaging evidence of acupuncture in cognitive impairment following ischemic stroke: a systematic review.

Frontiers in neuroscience·2026
Same author

Association of tongue diagnosis-guided acupuncture with postoperative nausea and vomiting in high-risk laparoscopic surgery patients.

American journal of translational research·2025
Same journal

Reassessing the Proposed Creatine-PrP Axis in Endometriosis: Methodological and Mechanistic Considerations.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same journal

IL-7R-Enriched Extracellular Vesicles From the Thymus Drive Colitis via Promoting Neutrophil Extracellular Trap Formation.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same journal

Oral Prebiotic Polysaccharide Hydrogels Sustaining Colon Antibody Release Alleviate Inflammatory Bowel Disease.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same journal

Systematic Phosphorus-Driven Structural and Field Engineering of n-a-Si:H for Flexible n-a-Si:H/Te Near-Infrared Photodetectors.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same journal

Chemically Gradient Ordered Nanodomains Enable Large Tensile Ductility in Gigapascal Lightweight Refractory High-Entropy Alloys.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same journal

Single-Molecule Characterization of Bacterial Factor-Dependent Transcription Activation by Rob.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
See all related articles

Related Experiment Video

Updated: Jun 20, 2026

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
10:26

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

Published on: January 16, 2015

Allosteric Inhibition of Polycomb Repressive Complex 2 by an EZH2-Selective Small Molecule Inhibitor.

Ting Cao1,2,3, Dongdong Liu1,4, Haishan Gao2,3

  • 1Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 18, 2026
PubMed
Summary
This summary is machine-generated.

A new small molecule, C36, selectively inhibits EZH2/PRC2 via a novel non-competitive mechanism. This discovery offers a promising avenue for developing targeted cancer therapies with reduced side effects.

Keywords:
EZH2 inhibitorPRC2allosteric mechanismcancer immunotherapy

More Related Videos

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome
11:15

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome

Published on: March 2, 2018

Related Experiment Videos

Last Updated: Jun 20, 2026

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
10:26

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

Published on: January 16, 2015

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome
11:15

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome

Published on: March 2, 2018

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Polycomb Repressive Complex 2 (PRC2) is crucial for gene transcription repression.
  • Aberrant EZH2 activity and H3K27 methylation are implicated in human cancers.
  • Existing SAM-competitive inhibitors target both EZH1 and EZH2.

Purpose of the Study:

  • To characterize a novel small molecule inhibitor, C36, targeting EZH2/PRC2.
  • To elucidate the non-competitive inhibition mechanism of C36.
  • To evaluate C36's therapeutic potential in preclinical cancer models.

Main Methods:

  • Biochemical assays to assess PRC2 inhibition.
  • Cryo-electron microscopy (Cryo-EM) for structural determination.
  • Cellular and xenograft tumor models for efficacy and toxicity assessment.
  • Multi-omics analyses to identify direct targets.

Main Results:

  • C36 selectively inhibits EZH2/PRC2, not EZH1/PRC2, through a novel non-competitive mechanism.
  • Cryo-EM revealed C36 binds to a unique pocket, inducing conformational changes and disrupting allosteric communication.
  • C36 demonstrated potent inhibition of H3K27 trimethylation and tumor growth with low hematotoxicity.
  • C36 uncovered IFNB1 as a direct PRC2 target and enhanced anti-tumor efficacy in combination with PD-1 blockade.

Conclusions:

  • C36 represents a new class of allosteric EZH2/PRC2 inhibitors.
  • Selective EZH2 inhibition offers a potential therapeutic strategy for cancers.
  • C36 shows promise for combination therapy, particularly with immunotherapy.