Natalizumab
Identification
- Summary
Natalizumab is a monoclonal anti-integrin antibody which binds to the alpha 4 subunit of integrins to prevent migration of immune cells, and is used to treat Crohn's disease or multiple sclerosis.
- Brand Names
- Tysabri
- Generic Name
- Natalizumab
- DrugBank Accession Number
- DB00108
- Background
Humanized IgG4k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML). It was returned to market July, 2006.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
- Not Available
- Synonyms
- Anti-alpha4 integrin
- Anti-VLA4
- Natalizumab
- External IDs
- AN100226M
Pharmacology
- Indication
For treatment of multiple sclerosis.
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
In multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells, and their counter-receptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be a secondary result of its blockade of the molecular interaction of a 4b 1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. α4-integrin is required for white blood cells to move into organs, therefore, natalizumab prevents these immune cells from crossing blood vessel walls to reach affected organs thereby decreasing inflamation.
- Mechanism of action
Binds to the α4-subunit of α4b 1 and α4b 7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s).
Target Actions Organism AIntegrin alpha-4 antibodyHumans ULow affinity immunoglobulin gamma Fc region receptor III-B Not Available Humans UIntercellular adhesion molecule 1 Not Available Humans UHigh affinity immunoglobulin gamma Fc receptor I Not Available Humans - Absorption
Not Available
- Volume of distribution
- 5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients]
- 5.2 ± 2.8 L [Crohn's Disease (CD) Patients]
- Protein binding
Not Available
- Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
- Route of elimination
Not Available
- Half-life
11 ± 4 days
- Clearance
- 16 +/- 5 mL/hour [patients with MS who did not have PML receiving the repeat IV administration of a 300 mg dose]
- 22 +/- 22 mL/hour [Patients with Crohn's Disease receiving the repeat IV administration of a 300 mg dose]
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Natalizumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Natalizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Natalizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Natalizumab. Aducanumab The risk or severity of adverse effects can be increased when Natalizumab is combined with Aducanumab. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Natalizumab. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Natalizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Natalizumab. Alirocumab The risk or severity of adverse effects can be increased when Natalizumab is combined with Alirocumab. Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Natalizumab. 
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- No interactions found.
Products
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- Antegren
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tysabri Solution 300 mg / 15 mL Intravenous Biogen 2006-11-21 Not applicable Canada 
Tysabri Injection 300 mg/15mL Intravenous Biogen Inc. 2004-11-23 Not applicable US 
Tysabri Injection, solution, concentrate 300 mg Intravenous Biogen Netherlands B.V. 2020-12-15 Not applicable EU 
Tysabri Injection 300 mg/15mL Intravenous Elan Pharmaceuticals 2004-11-23 2016-06-30 US
Categories
- ATC Codes
- L04AA23 — Natalizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunologic Factors
- Immunomodulatory Agents
- Immunoproteins
- Immunosuppressive Agents
- Integrin Receptor Antagonist
- Proteins
- Selective Immunosuppressants
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 3JB47N2Q2P
- CAS number
- 189261-10-7
References
- General References
- Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, Vyhnalek P, Zadorova Z, Palmer T, Donoghue S: Natalizumab for active Crohn's disease. N Engl J Med. 2003 Jan 2;348(1):24-32. [Article]
- External Links
- PubChem Substance
- 46505849
- 354770
- ChEMBL
- CHEMBL1201607
- Therapeutic Targets Database
- DAP001094
- PharmGKB
- PA164747191
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Natalizumab
- FDA label
- Download (96 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Not Available Crohn's Disease (CD) 1 4 Completed Not Available Disseminated Sclerosis 1 4 Completed Basic Science Disseminated Sclerosis 1 4 Completed Diagnostic Disseminated Sclerosis 1 4 Completed Supportive Care Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Completed Treatment Disseminated Sclerosis 1 4 Completed Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 3 4 Recruiting Other Disseminated Sclerosis 1 4 Recruiting Treatment Disseminated Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Recruiting Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Biogen Idec Inc.
- Elan Pharmaceuticals Inc.
- Hospira Inc.
- Dosage Forms
Form Route Strength Injection Intravenous 300 mg/15mL Injection, solution, concentrate Intravenous 300 mg Injection, solution, concentrate Intravenous; Parenteral Solution Intravenous 300 mg / 15 mL Injection, solution, concentrate Intravenous Solution, concentrate Intravenous 300 mg Injection, solution, concentrate Intravenous 20 mg/1ml - Prices
Unit description Cost Unit Tysabri 300 mg/15 ml vial 207.31USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Metal ion binding
- Specific Function
- Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are...
- Gene Name
- ITGA4
- Uniprot ID
- P13612
- Uniprot Name
- Integrin alpha-4
- Molecular Weight
- 114898.745 Da
References
- Sheremata WA, Minagar A, Alexander JS, Vollmer T: The role of alpha-4 integrin in the aetiology of multiple sclerosis: current knowledge and therapeutic implications. CNS Drugs. 2005;19(11):909-22. [Article]
- Niino M, Bodner C, Simard ML, Alatab S, Gano D, Kim HJ, Trigueiro M, Racicot D, Guerette C, Antel JP, Fournier A, Grand'Maison F, Bar-Or A: Natalizumab effects on immune cell responses in multiple sclerosis. Ann Neurol. 2006 May;59(5):748-54. [Article]
- Stuve O, Bennett JL: Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri) in inflammatory diseases. CNS Drug Rev. 2007 Spring;13(1):79-95. [Article]
- Craddock CF, Nakamoto B, Andrews RG, Priestley GV, Papayannopoulou T: Antibodies to VLA4 integrin mobilize long-term repopulating cells and augment cytokine-induced mobilization in primates and mice. Blood. 1997 Dec 15;90(12):4779-88. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent...
- Gene Name
- FCGR3B
- Uniprot ID
- O75015
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-B
- Molecular Weight
- 26215.64 Da
References
- Weber F, Breustedt D, Schlicht S, Meyer CA, Niewoehner J, Ebeling M, Freskgard PO, Bruenker P, Singer T, Reth M, Iglesias A: First Infusion Reactions are Mediated by FcgammaRIIIb and Neutrophils. Pharm Res. 2018 Jun 27;35(9):169. doi: 10.1007/s11095-018-2448-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Virus receptor activity
- Specific Function
- ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial api...
- Gene Name
- ICAM1
- Uniprot ID
- P05362
- Uniprot Name
- Intercellular adhesion molecule 1
- Molecular Weight
- 57824.785 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Receptor signaling protein activity
- Specific Function
- High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
- Gene Name
- FCGR1A
- Uniprot ID
- P12314
- Uniprot Name
- High affinity immunoglobulin gamma Fc receptor I
- Molecular Weight
- 42631.525 Da
References
- Dudek S, Weissmuller S, Anzaghe M, Miller L, Sterr S, Hoffmann K, Hengel H, Waibler Z: Human Fcgamma receptors compete for TGN1412 binding that determines the antibody's effector function. Eur J Immunol. 2019 Jul;49(7):1117-1126. doi: 10.1002/eji.201847924. Epub 2019 Apr 29. [Article]
Drug created on June 13, 2005 13:24 / Updated on July 24, 2021 14:58