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

You might also read

Related Articles

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

Sort by
Same author

Dysregulation of the Tau-Microtubule-End-Binding Protein Axis in Alzheimer's Disease and Related Tauopathies.

International journal of molecular sciences·2026
Same author

From anti-fungal to potential neurotherapeutic: Posaconazole as an effective inhibitor of cellular TDP-43 pathology.

bioRxiv : the preprint server for biology·2026
Same author

Engineering Murine Cross-Reactivity Into an Affibody to Human Death Receptor 5.

Biotechnology and bioengineering·2026
Same author

Lysosome-Acidifying Nanoparticles Rescue A30P α-Synuclein Induced Neuronal Death in Cellular and Drosophila Models of Parkinson's Disease.

Advanced healthcare materials·2026
Same author

Lysosome trafficking across intracellular and intercellular networks in the brain.

Frontiers in molecular neuroscience·2026
Same author

Multiplexed Dark FRET Biosensors: An Accessible Live-Cell Platform for Target- and Cell-Specific Monitoring of Protein-Protein Interactions in 2D and 3D Model Systems.

ACS sensors·2026

Related Experiment Video

Updated: Mar 2, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K

An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors.

Chih Hung Lo1, Nagamani Vunnam1, Andrew K Lewis1

  • 11 Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.

SLAS Discovery : Advancing Life Sciences R & D
|May 23, 2017
PubMed
Summary
This summary is machine-generated.

New small molecules, zafirlukast and triclabendazole, inhibit tumor necrosis factor receptor 1 (TNFR1) activation by targeting receptor interactions, not ligands. This approach avoids side effects and offers a new strategy for inflammatory and autoimmune diseases.

Keywords:
NF-κB inhibitionpre-ligand assembly domainreceptor–receptor interactiontime-resolved FRETtumor necrosis factor receptor 1

More Related Videos

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

13.1K
A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
08:43

A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules

Published on: March 10, 2017

11.0K

Related Experiment Videos

Last Updated: Mar 2, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K
Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

13.1K
A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
08:43

A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules

Published on: March 10, 2017

11.0K

Area of Science:

  • Immunology
  • Pharmacology
  • Molecular Biology

Background:

  • Tumor necrosis factor receptor 1 (TNFR1) signaling is crucial for inflammatory responses.
  • Dysregulation of TNFR1 ligands is linked to inflammatory and autoimmune diseases.
  • Current treatments targeting ligands cause off-target side effects.

Purpose of the Study:

  • To develop a novel screening method to identify small molecules targeting TNFR1 activation.
  • To find compounds that inhibit TNFR1 signaling without blocking ligand binding.
  • To establish a new therapeutic strategy for TNFR1-mediated diseases.

Main Methods:

  • Development of a TNFR1 Förster Resonance Energy Transfer (FRET) biosensor in living cells.
  • High-throughput screening using a fluorescence lifetime imaging microscopy platform.
  • Biochemical assays and computational docking to elucidate compound mechanisms.

Main Results:

  • Identified zafirlukast and triclabendazole as inhibitors of TNFR1-induced IκBα degradation and NF-κB activation.
  • Zafirlukast disrupts TNFR1 pre-ligand assembly domain (PLAD) interactions.
  • Triclabendazole acts via an allosteric mechanism.
  • Neither compound inhibited ligand binding to TNFR1.

Conclusions:

  • Demonstrated the feasibility of inhibiting receptor activation by targeting receptor-receptor interactions.
  • This strategy offers a potential therapeutic approach for inflammatory and autoimmune diseases.
  • The developed biosensor and screening platform are applicable to other oligomeric receptors.