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. It targets α4β1 integrin (VLA-4) on leukocytes to block interaction with vascular cell adhesion molecule 1 (VCAM-1) on inflamed endothelium, thus inhibiting leukocyte extravasation into sites of inflammation. It is active in peripheral tissues and the central vervous system.
Targeting cell migration-related molecules in immune conditions (and cancer) is regarded as a valid approach for the development of novel anti-inflammatory therapeutics [3]. The design and synthesis of this antibody was originally described in a 1997 publication [2].

The first natalizumab biosimilar was approved by the FDA in August 2023. Like the originator/reference agent, Tyruko® (natalizumab-sztn; Sandoz Inc.) is indicated for relapsing forms of multiple sclerosis and moderate-severe active Crohn's disease (when conventional therapies, including TNF-α inhibitors, are inadequate or not tolerated).
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: natalizumab

1. Kekre N, Kim HT, Hofer J, Ho VT, Koreth J, Armand P, Nikiforow S, Gooptu M, Romee R, Alyea EP et al.. (2021)
Phase II trial of natalizumab with corticosteroids as initial treatment of gastrointestinal acute graft-versus-host disease.
Bone Marrow Transplant, 56 (5): 1006-1012. [PMID:32895491]
2. Léger OJ, Yednock TA, Tanner L, Horner HC, Hines DK, Keen S, Saldanha J, Jones ST, Fritz LC, Bendig MM. (1997)
Humanization of a mouse antibody against human alpha-4 integrin: a potential therapeutic for the treatment of multiple sclerosis.
Hum Antibodies, 8 (1): 3-16. [PMID:9265500]
3. Mackay CR. (2008)
Moving targets: cell migration inhibitors as new anti-inflammatory therapies.
Nat Immunol, 9 (9): 988-98. [PMID:18711436]
4. No authors listed. (2004)
Natalizumab: AN 100226, anti-4alpha integrin monoclonal antibody.
Drugs R D, 5 (2): 102-7. [PMID:15293871]