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

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

7.0K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.0K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

8.9K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
8.9K

You might also read

Related Articles

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

Sort by
Same author

SIRT2-mediated deacetylation activates USP22 catalytic function for PD-L1 protein stabilization and tumor immune escape.

The Journal of clinical investigation·2026
Same author

A novel S1P analogue/MLCK inhibitory peptide-encargoed nanocarrier to attenuate lung vascular leak.

American journal of respiratory cell and molecular biology·2026
Same author

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer.

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

Calibrated Integrated Backscatter Is Associated With Increased Left Ventricular Concentricity and Left Atrial Stiffness in Resistance Trained Individuals Using Anabolic-Androgenic Steroids.

Echocardiography (Mount Kisco, N.Y.)·2026
Same author

Involvement of Non-Muscle Myosin Light Chain Kinase Nitration in Molecular Regulation of Inflammation-Induced Endothelial Cell Barrier Dysfunction.

Cells·2026
Same author

ERM Inhibition Confers Ferroptosis Resistance through ROS-Induced NRF2 Signaling.

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

Modulating Surface Potential and Electron/Hole Overlap of Singlet Excited State in Asymmetry End-Capped Dimeric Acceptors for Efficient and Stretchable Organic Solar Cells.

Angewandte Chemie (International ed. in English)·2026
Same journal

Interfacial Donor-Acceptor Engineering in MOFs: Synergizing Self-Excitation and External Charge Utilization for High-Efficiency Photocatalytic Hydrogen Evolution.

Angewandte Chemie (International ed. in English)·2026
Same journal

Spin-Dominated Electroreduction of Oxygen to Hydrogen Peroxide: A Case Study With Molecular Model Catalysts.

Angewandte Chemie (International ed. in English)·2026
Same journal

Catalytic Hydrosilylation Deoxygenation: Synthesizing Polysiloxanes While Upcycling Polymers to Alkanes.

Angewandte Chemie (International ed. in English)·2026
Same journal

Polymerization Kinetics-Mediated Topological Entanglement Enables High-Contrast 3D Self-Morphing in Hydrogels.

Angewandte Chemie (International ed. in English)·2026
Same journal

An Efficient Photocatalytic Process for Hydrogen Production and Acetic Acid Synthesis on FAPbBr<sub>3</sub> Perovskite.

Angewandte Chemie (International ed. in English)·2026
See all related articles

Related Experiment Video

Updated: Apr 24, 2026

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

11.7K

GRP78 Selective Inhibitors From a Direct-to-Biology Strategy.

Xiaoyi Zhu1, Carlee A Trindl1, Qiu Li2

  • 1College of Medicine, Department of Pharmacology and Therapeutics, Center For Inflammation Science and Systems Medicine, The Herbert Wertheim UF Scripps Institute For Biomedical Innovation and Technology, University of Florida, Jupiter, Florida, USA.

Angewandte Chemie (International Ed. in English)
|April 23, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a GRP78-selective inhibitor for cancer therapy. This compound targets GRP78, a key protein in cancer cells, leading to cancer cell death and offering a precise therapeutic approach.

Keywords:
BiPER stressGRP78HSP70HSPA5lung cancerproteostasis

More Related Videos

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

2.3K
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
08:31

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

4.8K

Related Experiment Videos

Last Updated: Apr 24, 2026

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

11.7K
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

2.3K
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
08:31

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

4.8K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Cancer cells exhibit increased protein homeostasis demands, making proteostasis machinery a therapeutic target.
  • The 70 kDa heat shock protein (HSP70) family is differentially regulated in cancers, necessitating isoform-selective targeting to avoid toxicity.
  • GRP78 (HSPA5/BiP), an endoplasmic reticulum-resident HSP70, is crucial for secretory protein homeostasis and the unfolded protein response (UPR).

Purpose of the Study:

  • To develop a GRP78-selective inhibitor using a direct-to-biology (D2B) strategy.
  • To optimize a dipeptide-based scaffold for selective binding to GRP78 over other HSP70s.
  • To validate the therapeutic potential of a GRP78-selective inhibitor in lung cancer models.

Main Methods:

  • Employed a direct-to-biology (D2B) strategy to optimize a dipeptide scaffold.
  • Synthesized and characterized lead compound 12 for GRP78 selectivity and binding.
  • Assessed compound 12's efficacy in A549 lung cancer cells (2D and 3D cultures) and confirmed GRP78 engagement and inhibition.

Main Results:

  • Identified a lead compound, 12, that potently and selectively inhibits GRP78.
  • Compound 12 binds to the substrate-binding pocket of GRP78.
  • Demonstrated that GRP78 inhibition by compound 12 leads to A549 lung cancer cell death in vitro.
  • Confirmed GRP78 engagement and that its inhibition is the primary mode of action.

Conclusions:

  • This study presents the first GRP78-selective inhibitor capable of inhibiting substrate binding.
  • The developed compound shows promise as a targeted therapeutic agent for cancers reliant on GRP78.
  • Isoform-selective targeting of HSP70 family members, like GRP78, offers a viable strategy for cancer therapy with potentially reduced toxicity.