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

Antiasthma Drugs: Leukotriene Modifiers01:19

Antiasthma Drugs: Leukotriene Modifiers

371
Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
371
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.5K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

177
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
177
Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs01:25

Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs

357
Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
357
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

9.0K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.0K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

7.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K

You might also read

Related Articles

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

Sort by
Same author

Interpretable early mortality prediction in oncology ICU patients: A dual-cohort validation of a LASSO-XGBoost-SHAP framework.

Digital health·2026
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

Body mass index and achievement of minimal disease activity in psoriatic arthritis across different classes of advanced therapy.

Rheumatology (Oxford, England)·2026
Same author

SREBPs in Metabolic Reprogramming and Disease: Mechanisms and Therapeutic Potential.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology·2026
Same author

Tetrahedral Framework Nucleic Acids Re-establish Immune Tolerance and Restore Thyroid Function in Hashimoto's Thyroiditis via NOTCH1 Signaling Pathway Inhibition.

ACS applied materials & interfaces·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

Related Experiment Video

Updated: Jul 25, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.5K

Zafirlukast Is a Promising Scaffold for Selectively Inhibiting TNFR1 Signaling.

Nagamani Vunnam1, Mu Yang2, Chih Hung Lo1

  • 1Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, United States.

ACS Bio & Med Chem Au
|June 26, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed new zafirlukast analogues to target Tumor Necrosis Factor Receptor 1 (TNFR1) for inflammatory diseases. The best analogue showed improved potency and efficacy, offering a promising lead for therapeutic development.

More Related Videos

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

12.3K
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

12.5K

Related Experiment Videos

Last Updated: Jul 25, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.5K
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

12.3K
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

12.5K

Area of Science:

  • Biochemistry
  • Immunology
  • Pharmacology

Background:

  • Tumor necrosis factor (TNF) is implicated in inflammatory and autoimmune diseases like rheumatoid arthritis and Crohn's disease.
  • TNF's effects are mediated by TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2).
  • TNFR1-specific inhibition is crucial for targeted therapy to avoid side effects.

Purpose of the Study:

  • To synthesize and evaluate analogues of zafirlukast for improved potency and specificity in TNFR1 signaling.
  • To identify novel small molecules that modulate TNFR1 conformational states for therapeutic potential.
  • To investigate the binding and functional effects of these analogues on TNFR1 and TNFR2.

Main Methods:

  • Engineered a time-resolved fluorescence resonance energy transfer (FRET) biosensor for high-throughput screening.
  • Synthesized 16 zafirlukast analogues and tested them using cell-based functional assays.
  • Measured NF-κB activation, IκBα efficiency, and receptor conformational changes via FRET.

Main Results:

  • Identified three analogues with significantly improved efficacy and potency for TNFR1 signaling.
  • The best analogue demonstrated a two-order of magnitude increase in relative potency and reduced NF-κB activation by 2.2-fold.
  • Analogues induced conformational changes in TNFR1 but did not block TNF binding; they bound TNFR2 in vitro without inhibiting its function.

Conclusions:

  • The developed zafirlukast analogues represent promising leads for TNFR1-specific inhibitors in inflammatory diseases.
  • Further optimization of the zafirlukast scaffold is needed to achieve full NF-κB inhibition.
  • These compounds can serve as valuable tools for studying TNF receptor activation mechanisms.