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

Enzyme Inhibition01:30

Enzyme Inhibition

77.9K
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.
77.9K
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

1.7K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.7K
Feedback Inhibition00:46

Feedback Inhibition

53.7K
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
53.7K
Enzymes02:34

Enzymes

80.7K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
80.7K
Combined Effects of Drugs: Antagonism01:30

Combined Effects of Drugs: Antagonism

8.3K
The combined effects of drugs can result in various interactions, of which an important type is antagonism. Antagonism is a mechanism where one drug inhibits or counteracts the effects of another drug. Antagonism can occur through various means, including receptor binding, allosteric modulation, functional interaction, chemical reactions, and pharmacokinetic processes.
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
8.3K
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

520
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
520

You might also read

Related Articles

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

Sort by
Same author

A literature review: progress in the study of plastic bronchitis.

Frontiers in pediatrics·2026
Same author

Correction to "Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug Resistant Mutants and Adverse Effects".

Journal of medicinal chemistry·2026
Same author

Thoracoscopic near-infrared localization and division of H-type tracheoesophageal fistulas in newborns: A case series.

Journal of pediatric surgery·2026
Same author

An Improved Red-Billed Blue Magpie Optimization for Function Optimization and Engineering Problems.

Biomimetics (Basel, Switzerland)·2026
Same author

Exploratory study on the efficacy of Lingze mixture in gouty arthritis rats and preliminary analysis of its potential mechanisms via transcriptome sequencing.

Scientific reports·2025
Same author

Regulation of Interfacial Ion Transport via Honeycomb-Architected Covalent Organic Frameworks for Lithium Metal Batteries.

Advanced materials (Deerfield Beach, Fla.)·2025

Related Experiment Video

Updated: Jun 6, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

76

A Dual-Target and Dual-Mechanism Design Strategy by Combining Inhibition and Degradation Together.

Yongbo Liu1, Xiuyun Sun2, Qianlong Liu1

  • 1MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, State Key Laboratory of Molecular Oncology, Tsinghua University, Beijing 100084, China.

Journal of the American Chemical Society
|December 2, 2024
PubMed
Summary

A new bifunctional molecule, YB-3-17, simultaneously inhibits mTOR and degrades GSPT1, offering a promising precision therapy for glioblastoma. This approach overcomes resistance and enhances efficacy in preclinical models.

More Related Videos

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

9.4K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K

Related Experiment Videos

Last Updated: Jun 6, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

76
High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

9.4K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Glioblastoma is an aggressive brain tumor with poor survival rates, necessitating novel therapeutic strategies.
  • Mammalian targets of rapamycin (mTOR) and G1 to S phase transition 1 gene (GSPT1) are overexpressed in glioblastoma, contributing to tumor growth.
  • Existing mTOR inhibitors and GSPT1-targeting therapies show limited clinical success due to resistance and efficacy challenges.

Purpose of the Study:

  • To develop a novel bifunctional molecule combining mTOR inhibition and GSPT1 degradation for glioblastoma treatment.
  • To evaluate the efficacy and safety of the bifunctional molecule YB-3-17 in preclinical glioblastoma models.
  • To demonstrate the feasibility of integrating inhibitor and degrader properties into a single molecule.

Main Methods:

  • Design and synthesis of YB-3-17, a novel bifunctional molecule targeting both mTOR and GSPT1.
  • In vitro assessment of YB-3-17's efficacy in glioblastoma cell lines, comparing it to standalone therapies.
  • RNA-sequencing analysis to elucidate molecular mechanisms of YB-3-17.
  • In vivo studies in mice to evaluate tumor growth inhibition and safety.

Main Results:

  • YB-3-17 robustly inhibits mTOR and selectively degrades GSPT1, demonstrating superior efficacy over standalone treatments in glioblastoma cell lines.
  • RNA-seq analysis revealed distinct advantages of YB-3-17 compared to mTOR inhibitor treatment alone.
  • YB-3-17 demonstrated safe and effective inhibition of glioblastoma tumor growth in preclinical mouse models.

Conclusions:

  • YB-3-17 represents a first-in-class bifunctional molecule combining mTOR inhibition and GSPT1 degradation for glioblastoma.
  • This dual-action approach offers enhanced efficacy and overcomes resistance mechanisms in glioblastoma.
  • The successful integration of inhibitor and degrader functionalities into a single molecule opens new avenues for precision cancer therapy.