DT-Web

DB00108 - Natalizumab


Identification
Name Natalizumab
Accession Number DB00108 (BIOD00083, BTD00083)
Type biotech
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 Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML).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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight Not Available
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of multiple sclerosis.
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).
Absorption Not Available
Protein binding Not Available
Biotransformation Most likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
ado-trastuzumab emtansine Avoid combination due to the increased risk of infection.
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.
BRENTUXIMAB VEDOTIN Avoid combination due to the increased risk of concurrent infection.
Canakinumab Avoid combination due to the increased risk of infection.
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.
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.
Certolizumab pegol Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
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.
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.
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.
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.
golimumab Avoid combination due to the increased chance of infection.
Homoharringtonine Avoid combination due to the increased risk of infection.
Paclitaxel Avoid combination due to the increased risk of infection.
Tacrolimus Tacrolimus may increase the toxic/adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
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.
Temsirolimus Temsirolimus may increase the toxicity of Natalizumab. Concomitant therapy should be avoided.
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.
Teriflunomide Avoid combination due to the increased risk of infection.
Thalidomide Thalidomide may increase the adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
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.
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.
Tofacitinib Avoid combination due to the increased risk of infection.
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.
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.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Tretinoin Oral tretinoin may increase the adverse/toxic effects of Natalizumab. Concurrent therapy should be avoided.
Valrubicin Valrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.
Vinblastine Concomitant Vinblastine 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.
Vinorelbine Concomitant Vinorelbine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Food Interactions Not Available

Targets


Integrin alpha-4
Name Integrin alpha-4
Gene Name ITGA4
Pharmacological action yes
Actions antibody
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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6049
Low affinity immunoglobulin gamma Fc region receptor III-B
Name Low affinity immunoglobulin gamma Fc region receptor III-B
Gene Name FCGR3B
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.5375
Complement C1r subcomponent
Name Complement C1r subcomponent
Gene Name C1R
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.4454
Complement C1q subcomponent subunit A
Name Complement C1q subcomponent subunit A
Gene Name C1QA
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.4624
Complement C1q subcomponent subunit B
Name Complement C1q subcomponent subunit B
Gene Name C1QB
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.4633
Complement C1q subcomponent subunit C
Name Complement C1q subcomponent subunit C
Gene Name C1QC
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.4632
Low affinity immunoglobulin gamma Fc region receptor III-A
Name Low affinity immunoglobulin gamma Fc region receptor III-A
Gene Name FCGR3A
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.5371
High affinity immunoglobulin gamma Fc receptor I
Name High affinity immunoglobulin gamma Fc receptor I
Gene Name FCGR1A
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.625
Low affinity immunoglobulin gamma Fc region receptor II-a
Name Low affinity immunoglobulin gamma Fc region receptor II-a
Gene Name FCGR2A
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.5458
Low affinity immunoglobulin gamma Fc region receptor II-b
Name Low affinity immunoglobulin gamma Fc region receptor II-b
Gene Name FCGR2B
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.5415
Low affinity immunoglobulin gamma Fc region receptor II-c
Name Low affinity immunoglobulin gamma Fc region receptor II-c
Gene Name FCGR2C
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
DTHybrid score 1.5513
Intercellular adhesion molecule 1
Name Intercellular adhesion molecule 1
Gene Name ICAM1
Pharmacological action unknown
Actions Not Available
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.7716

Predictions


Id Partner name Gene Name Score
2782 Complement C1s subcomponent C1S 0.7705
1901 CD44 antigen CD44 0.4887
75 B-lymphocyte antigen CD20 MS4A1 0.3345
2020 Stromal cell-derived factor 1 CXCL12 0.3262
309 Antithrombin-III SERPINC1 0.2071
724 Interleukin-2 receptor alpha chain IL2RA 0.1966
717 Interleukin-2 receptor subunit beta IL2RB 0.1965
844 Epidermal growth factor receptor EGFR 0.1518
93 CAMPATH-1 antigen CD52 0.1474
777 Tumor necrosis factor TNF 0.1474
757 Fusion glycoprotein F0 F 0.147
4875 Fusion glycoprotein F0 F 0.147
744 Myeloid cell surface antigen CD33 CD33 0.1349
793 T-cell surface antigen CD2 CD2 0.1302
1733 Vitronectin VTN 0.1155
572 Integrin alpha-L ITGAL 0.1081
5901 T-cell surface glycoprotein CD3 zeta chain CD247 0.108
1789 Lymphotoxin-alpha LTA 0.108
302 T-cell surface glycoprotein CD3 epsilon chain CD3E 0.108
5900 T-cell surface glycoprotein CD3 gamma chain CD3G 0.108
5899 T-cell surface glycoprotein CD3 delta chain CD3D 0.108
1269 Tumor necrosis factor receptor superfamily member 1B TNFRSF1B 0.1079
955 Complement C5 C5 0.1033
5898 Complement C3 C3 0.103
2039 Integrin beta-3 ITGB3 0.1005
488 Integrin alpha-IIb ITGA2B 0.1004
183 Vascular endothelial growth factor A VEGFA 0.0927
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.0836
554 Low-density lipoprotein receptor LDLR 0.0664
3811 Cytochrome P450 19A1 CYP19A1 0.0545
290 Prostaglandin G/H synthase 2 PTGS2 0.0457
660 T-cell surface glycoprotein CD1a CD1A 0.0172
6063 Major histocompatibility complex class I-related gene protein MR1 0.0172
5955 T-cell surface glycoprotein CD4 CD4 0.0172
6065 Integrin beta-1 ITGB1 0.0172
6066 Integrin alpha-V ITGAV 0.0172
942 T-lymphocyte activation antigen CD86 CD86 0.0138
4878 Glycoprotein hormones alpha chain CGA 0.0024
1072 Granzyme B GZMB 0.0024
4189 Alpha-galactosidase A GLA 0.0024
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0024
4889 Ig epsilon chain C region IGHE 0.0024
4877 Beta-mannanase man 0.0024
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0024
4850 Beta-2-glycoprotein 1 APOH 0.0024
4852 Reticulon-4 receptor RTN4R 0.0024
4880 Membrane cofactor protein CD46 0.0024
4856 CD209 antigen CD209 0.0024
4869 Major capsid protein A430L 0.0024
4845 ADAM 33 ADAM33 0.0024
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0024
1354 Beta-glucuronidase GUSB 0.0024
442 Envelope glycoprotein gp41 0.0024
4859 Envelope glycoprotein env 0.0024
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0024
4721 Beta-1,4-mannanase manA 0.0024
3352 Structural polyprotein Not Available 0.0024
3628 Structural polyprotein Not Available 0.0024
4892 Structural polyprotein Not Available 0.0024
1184 Interferon beta IFNB1 0.0021
6858 Inactive carboxylesterase 4 CES1P1 0.0021
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0021
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0021
4890 Hemagglutinin HA 0.0021
6566 Hemagglutinin Not Available 0.0021
4861 Interleukin-6 receptor alpha chain IL6R 0.0021
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0021
1379 Interleukin-12 subunit beta IL12B 0.0021
3837 Cytokine receptor common beta chain CSF2RB 0.0021
3444 Cyanovirin-N Not Available 0.002
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.002
1859 Prostatic acid phosphatase ACPP 0.002
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.002
852 Heparin cofactor 2 SERPIND1 0.002
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.002
3140 Hemagglutinin-neuraminidase HN 0.002
3609 Hemagglutinin-neuraminidase HN 0.002
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.002
2297 Genome polyprotein Not Available 0.002
2322 Genome polyprotein Not Available 0.002
2694 Genome polyprotein Not Available 0.002
2719 Genome polyprotein Not Available 0.002
2860 Genome polyprotein Not Available 0.002
2928 Genome polyprotein Not Available 0.002
3160 Genome polyprotein Not Available 0.002
3260 Genome polyprotein Not Available 0.002
4783 Genome polyprotein Not Available 0.002
5726 Genome polyprotein Not Available 0.002
5779 Genome polyprotein Not Available 0.002
5867 Genome polyprotein Not Available 0.002
6253 Genome polyprotein Not Available 0.002
6301 Genome polyprotein Not Available 0.002
6380 Genome polyprotein Not Available 0.002
6381 Genome polyprotein Not Available 0.002
6437 Genome polyprotein Not Available 0.002
6520 Genome polyprotein Not Available 0.002
6521 Genome polyprotein Not Available 0.002
6652 Genome polyprotein Not Available 0.002
6734 Genome polyprotein Not Available 0.002
6735 Genome polyprotein Not Available 0.002
6736 Genome polyprotein Not Available 0.002
6737 Genome polyprotein Not Available 0.002
6738 Genome polyprotein Not Available 0.002
6739 Genome polyprotein Not Available 0.002
6744 Genome polyprotein Not Available 0.002
6748 Genome polyprotein Not Available 0.002
6894 Genome polyprotein Not Available 0.002
6898 Genome polyprotein Not Available 0.002
4666 Fucose-binding lectin PA-IIL lecB 0.0019
2372 Bifunctional tail protein 9 0.0019
4787 Envelope glycoprotein gp160 env 0.0019
4820 Envelope glycoprotein gp160 env 0.0019
5727 Envelope glycoprotein gp160 env 0.0019
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0018
3480 Mannan endo-1,4-beta-mannosidase manA 0.0017
64 Neuraminidase NA 0.0017
641 Neuraminidase NA 0.0017
2676 Neuraminidase NA 0.0017
3026 Neuraminidase NA 0.0017
3519 Neuraminidase NA 0.0017
6007 Neuraminidase NA 0.0017
595 Fibrinogen alpha chain FGA 0.0017
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0017
1439 Lactotransferrin LTF 0.0017
1243 Cathepsin D CTSD 0.0016
2430 Chondroitinase B cslB 0.0016
958 Insulin-like growth factor 1 receptor IGF1R 0.0016
6307 Ig gamma-2 chain C region IGHG2 0.0015
2581 Chondroitinase AC cslA 0.0015
6847 Lactase-phlorizin hydrolase LCT 0.0015
6500 Phospholipase A2 PLA2G1B 0.0015
2207 Rhodopsin RHO 0.0014
4785 Ig gamma-1 chain C region IGHG1 0.0013
4604 Liver carboxylesterase 1 CES1 0.0013
76 Nitric-oxide synthase, brain NOS1 0.0013
952 Dipeptidyl peptidase 4 DPP4 0.0011
3923 Cholinesterase BCHE 0.0011
20 Prostaglandin G/H synthase 1 PTGS1 0.001
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