Related Experiment Video
Updated: Jul 13, 2026

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs
Published on: February 2, 2024
Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?
Richard J Davenport1, James R Munday
1Global Chemistry, UCB-Group, Granta Park, Great Abington, Cambridge CB16GS, UK. richard.davenport@ucb-group.com
Abstract:
Inhibition of leucocyte trafficking by antagonism of the alpha4 (alpha4)-integrin has now been validated as a therapeutic approach for the treatment of inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). This validation has been overshadowed by three incidences of progressive multifocal leucoencaphalopathy (PML) in patients receiving natalizumab (Tysabri), a therapeutic monoclonal IgG antibody directed against alpha4-integrins. This led to the initial removal of natalizumab from the market. Following a safety review, it was reintroduced for the treatment of relapsing-remitting MS patients (with restrictions). This has led to a refocus on alpha4-integrins as a therapeutic target across the pharmaceutical industry. Recent advances in small molecule development are worth reviewing. New understanding of pharmacokinetics and selectivity will potentially contribute to the development of alpha4 antagonist with greater clinical efficacy and safety.
Related Concept Videos
Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
Intracellular Signaling Affects Focal Adhesions
Some...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
