natalizumab   Click here for help

GtoPdb Ligand ID: 6591

Synonyms: AN100226 | anti-alpha4 integrin | anti-VLA4 | Tysabri®
Approved drug Immunopharmacology Ligand
natalizumab is an approved drug (FDA (2004), EMA (2006))
Compound class: Antibody
Comment: Natalizumab was the first migration-inhibitory biological drug to be approved for inflammatory diseases.
Targeting cell migration-related molecules in immune conditions (and cancer) is regarded as a significant new focus for the development of novel anti-inflammatory therapeutics [3].
The design and synthesis of this antibody is described in [2], but the article is not open access.
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Summary of Clinical Use Click here for help
Used in the treatment of relapsing forms of multiple sclerosis, and in the management of Crohn's disease. However, natalizumab is not widely prescribed due to safety concerns around induction of progressive multifocal leukoencephalopathy (PML).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Binds to the α4-subunit of α4β1 and α4β7 integrins on leukocyte cell surfaces [2] which inhibits the adhesion of leukocytes to their counter-receptor, vascular cell adhesion molecule-1 (VCAM-1). This action limits T cell migration to inflamed tissue, thereby reducing active inflammation.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02176031 Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD Phase 2 Interventional Dana-Farber Cancer Institute Trial results indcated that initial treatment of acute gastrointestinal GvHD with natalizumab plus corticosteroids is safe, effective, and produces a durable response. 1
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