Repositioning Candidate Details
| Candidate ID: | R0031 |
| Source ID: | DB00108 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Natalizumab |
| Synonyms: | Anti-alpha4 integrin; Anti-VLA4; Natalizumab |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | 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 Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML).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. |
| CAS Number: | 189261-10-7 |
| Molecular Weight: | |
| DrugBank Indication: | For treatment of multiple sclerosis. |
| DrugBank 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 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. |
| DrugBank MoA: | 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). |
| Targets: | Integrin alpha-4 antibody; Low affinity immunoglobulin gamma Fc region receptor III-B; Intercellular adhesion molecule 1; High affinity immunoglobulin gamma Fc receptor I |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|