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Th1147 details
Primary information
ID10672
Therapeutic IDTh1147
Protein NameNatalizumab
SequenceNA
Molecular WeightNA
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting point61 (FAB fr
Half-life11 ± 4 days
DescriptionHumanized 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 Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML).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.
Indication/DiseaseFor treatment of multiple sclerosis.
PharmacodynamicsIn 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 ActionBinds 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).
ToxicityNA
MetabolismMost likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
AbsorptionNA
5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients, 5.2 ± 2.8 L [Crohn's Disease (CD) Patients]
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]
CategoriesAmino 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
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetIntegrin alpha-4,Low affinity immunoglobulin gamma Fc region receptor III-B,Intercellular adhesion molecule 1,High affinity immunoglobulin gamma Fc receptor I
Brand NameTysabri
CompanyBiogen Idec Inc.
Brand DescriptionBiogen Idec Inc.
Prescribed ForIt is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. Tysabri increases the risk of PML. It is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α.
Chemical NameNA
FormulationEach 15 mL dose contains 300 mg natalizumab; 123 mg sodium chloride, USP; 17.0 mg sodium phosphate, monobasic, monohydrate, USP; 7.24 mg sodium phosphate, dibasic, heptahydrate, USP; 3.0 mg polysorbate 80, USP/NF, in water for injection, USP at pH 6.1.
Physical Appearance Sterile, colorless, and clear to slightly opalescent concentrate
Route of AdministrationIntravenous infusion
Recommended DosageThe recommended dose of Tysabri for multiple sclerosis is 300 mg intravenous infusion over one hour every four weeks. The recommended dose of TysabriI for Crohn's disease is 300 mg intravenous infusion over one hour every four weeks. Tysabri should not be used with concomitant immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or concomitant inhibitors of TNF-α. Aminosalicylates may be continued during treatment with Tysabri.
ContraindicationTysabri is contraindicated in patients who have or have hadprogressive multifocal leukoencephalopathy (PML). It should not be administered to a patient who has had a hypersensitivity reaction to Tysabri. Observed reactions range from urticaria to anaphylaxis
Side EffectsProgressive Multifocal Leukoencephalopathy (PML), Hypersensitivity, Immunosuppression/Infections
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID10673
Therapeutic IDTh1147
Protein NameNatalizumab
SequenceNA
Molecular WeightNA
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting point61 (FAB fr
Half-life11 ± 4 days
DescriptionHumanized 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.
Indication/DiseaseFor treatment of multiple sclerosis.
PharmacodynamicsIn 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 ActionBinds 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).
ToxicityNA
MetabolismMost likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
AbsorptionNA
5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients, 5.2 ± 2.8 L [Crohn's Disease (CD) Patients]
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]
CategoriesAmino 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
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetIntegrin alpha-4,Low affinity immunoglobulin gamma Fc region receptor III-B,Intercellular adhesion molecule 1,High affinity immunoglobulin gamma Fc receptor I
Brand NameNA
CompanyElan Pharmaceuticals, Inc.
Brand DescriptionElan Pharmaceuticals, Inc.
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID10674
Therapeutic IDTh1147
Protein NameNatalizumab
SequenceNA
Molecular WeightNA
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting point61 (FAB fr
Half-life11 ± 4 days
DescriptionHumanized 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.
Indication/DiseaseFor treatment of multiple sclerosis.
PharmacodynamicsIn 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 ActionBinds 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).
ToxicityNA
MetabolismMost likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
AbsorptionNA
5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients, 5.2 ± 2.8 L [Crohn's Disease (CD) Patients]
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]
CategoriesAmino 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
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetIntegrin alpha-4,Low affinity immunoglobulin gamma Fc region receptor III-B,Intercellular adhesion molecule 1,High affinity immunoglobulin gamma Fc receptor I
Brand NameNA
CompanyBiogen Idec Canada Inc
Brand DescriptionBiogen Idec Canada Inc
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance Solution
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA


Primary information
ID10675
Therapeutic IDTh1147
Protein NameNatalizumab
SequenceNA
Molecular WeightNA
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting point61 (FAB fr
Half-life11 ± 4 days
DescriptionHumanized 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.
Indication/DiseaseFor treatment of multiple sclerosis.
PharmacodynamicsIn 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 ActionBinds 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).
ToxicityNA
MetabolismMost likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
AbsorptionNA
5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients, 5.2 ± 2.8 L [Crohn's Disease (CD) Patients]
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]
CategoriesAmino 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
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetIntegrin alpha-4,Low affinity immunoglobulin gamma Fc region receptor III-B,Intercellular adhesion molecule 1,High affinity immunoglobulin gamma Fc receptor I
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA