QuickView for Natalizumab (compound)

Summary
General Info

PubChem Substance

Name:	natalizumab
PubChem Substance ID:	3819475
Synonyms:	Tysabri; Natalizumab; 189261-10-7; Antegren; Immunoglobulin G4, anti-(human integrin alpha4) (human-mouse monoclonal AN100226 gamma4-chain), disulfide with human-mouse monoclonal AN100226 light chain, dimer

DrugBank

Identification

Name:	natalizumab
Name (isomeric):	DB00108
Drug Type:	biotech
Synonyms:	Anti-alpha4 integrin; Anti-VLA4
Brand:	Tysabri
Category:	Immunomodulatory Agents
CAS number:	189261-10-7

Pharmacology

Indication:	For treatment of multiple sclerosis.
Pharmacology:	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 effe... show more » 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. show less «
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).
Biotransformation:	Most likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
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]
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Valrubicin	Valrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.
Thioguanine	The immunosuppressant, Thioguanine, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Carmustine	Immunosuppressants such as carmustine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Temozolomide	The immunosuppressant, Temozolomide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Valrubicin	Valrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.
Thioguanine	The immunosuppressant, Thioguanine, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Carmustine	Immunosuppressants such as carmustine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Temozolomide	The immunosuppressant, Temozolomide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Thalidomide	Thalidomide may increase the adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
Tretinoin	Oral tretinoin may increase the adverse/toxic effects of Natalizumab. Concurrent therapy should be avoided.
Tositumomab	The immunosuppressant, Tositumomab, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Tacrolimus	Tacrolimus may increase the toxic/adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
Teniposide	The immunosuppressant, Teniposide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Cladribine	Immunosuppressants such as cladribine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Topotecan	The immunosuppressant, Topotecan, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Thiotepa	The immunosuppressant, Thiotepa, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
Cisplatin	Immunosuppressants such as cisplatin may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Vinorelbine	Concomitant Vinorelbine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Vincristine	Concomitant Vincristine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Carboplatin	Immunosuppressants such as natalizumab may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Bleomycin	Immunosuppressants like bleomycin may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Chlorambucil	Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Clofarabine	Immunosuppressants such as clofarabine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Vinblastine	Concomitant Vinblastine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Temsirolimus	Temsirolimus may increase the toxicity of Natalizumab. Concomitant therapy should be avoided.

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Targets

Integrin alpha-4

Low affinity immunoglobulin gamma Fc region receptor III-B

Complement C1r subcomponent

Complement C1q subcomponent subunit A

Complement C1q subcomponent subunit B

Complement C1q subcomponent subunit C

Low affinity immunoglobulin gamma Fc region receptor III-A

High affinity immunoglobulin gamma Fc receptor I

Low affinity immunoglobulin gamma Fc region receptor II-a

Low affinity immunoglobulin gamma Fc region receptor II-b

Low affinity immunoglobulin gamma Fc region receptor II-c

Intercellular adhesion molecule 1