Identification
- Summary
Daclizumab is a monoclonal anti-CD25 antibody that blocks the interleukin-2 receptor which is used to treat relapsing forms of multiple sclerosis.
- Generic Name
- Daclizumab
- DrugBank Accession Number
- DB00111
- Background
Humanized IgG1 Mab that binds to the human interleukin-2 receptor (anti-Tac or anti-CD25). Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. The human sequences were derived from the constant domains of human IgG1 and the variable framework regions of the Eu myeloma antibody. The murine sequences were derived from the complementarity-determining regions of a murine anti-Tac antibody.
On 22 April 2008, Roche Registration Limited chose to voluntarily withdraw the marketing authorization for their product Zenapax (daclizumab), as indicated for the prophylaxis of acute organ rejection in de novo allogeneic renal transplantation and used concomitantly with an immunosuppressive regimen like cyclosporine and corticosteroids in patients who are not hight immunized, for commercial reasons and confirmed that this decision was not related to any safety concerns associated with the use of Zenapax (daclizumab) 2. Regardless of the withdrawal of Zenapax, Biogen and Abbvie's Zinbryta (daclizumab), as indicated for the treatment of adult patients with relapsing forms of multiple sclerosis, was approved for use by the FDA in 2016 3.
Despite being approved for use, Zinbryta (daclizumab)'s complex pre-existing safety profile consisting of its restricted availability through a Risk Evaluation and Mitigation Strategy program 1 and its black box warning for possible hepatic injury, autoimmune hepatitis, and other immune mediated disorders 1 meant its therapeutic usage, adverse effects, and prescribing information was subject to continuous monitoring and updating.
Although Zinbryta (daclizumab) was available for patients as needed until 30 April 2018, Biogen and Abbvie announced a voluntary withdrawal of their product Zinbryta (daclizumab) from the global market on 2 March 2018 1. This withdrawal was concurrent to the European Medicines Agency announcement of a recall owing to 12 worldwide reports of serious inflammatory brain disorders associated with the use of Zinbryta (daclizumab) 1.
- Type
- Biotech
- Groups
- Investigational, Withdrawn
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6332H9808N1678O1989S42
- Protein Average Weight
- 142612.1 Da
- Sequences
>Humanized Anti-CD25 Heavy Chain 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEY NQKFKDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSSGPSV FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK
>Humanized Anti-CD25 Light Chain 1 DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPAR FSGSGSGTEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format- Synonyms
- Dacliximab
- Daclizumab
- Daclizumab beta
- External IDs
- RO 24-7375
- RO-24-7375
Pharmacology
- Indication
Zenapax is a humanized monoclonal antibody used for prevention of renal transplant rejection
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Relapsing multiple sclerosis •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Zenapax functions as an IL-2 receptor antagonist. Specifically it inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.
- Mechanism of action
Zenepax binds with high-affinity to the Tac subunit of the high-affinity IL-2 receptor complex and inhibits IL-2 binding. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes.
Target Actions Organism AInterleukin-2 receptor subunit alpha antibodyHumans AInterleukin-2 receptor subunit beta antibodyHumans ULow affinity immunoglobulin gamma Fc region receptor III-B Not Available Humans UComplement C1r subcomponent Not Available Humans UComplement C1q subcomponent subunit A Not Available Humans UComplement C1q subcomponent subunit B Not Available Humans UComplement C1q subcomponent subunit C Not Available Humans ULow affinity immunoglobulin gamma Fc region receptor III-A Not Available Humans UHigh affinity immunoglobulin gamma Fc receptor I Not Available Humans ULow affinity immunoglobulin gamma Fc region receptor II-a Not Available Humans ULow affinity immunoglobulin gamma Fc region receptor II-b Not Available Humans ULow affinity immunoglobulin gamma Fc region receptor II-c Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes.
- Route of elimination
Not Available
- Half-life
11-38 days
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Daclizumab is combined with Abatacept. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Daclizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Daclizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Daclizumab. Aducanumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Aducanumab. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zenapax Injection, solution, concentrate 25 mg Intravenous Roche Registration Limited 2016-09-08 2009-02-13 EU 
Zenapax Injection, solution, concentrate 25 mg/5mL Intravenous Genentech, Inc. 1997-12-10 2011-09-30 US 
Zenapax Injection, solution, concentrate 25 mg Intravenous Roche Registration Limited 2016-09-08 2009-02-13 EU Zenapax 5mg/ml Liquid 5 mg / mL Intravenous Hoffmann La Roche 2000-03-02 2011-10-17 Canada 
Zinbryta Solution 150 mg / mL Subcutaneous Biogen Not applicable Not applicable Canada
Categories
- ATC Codes
- L04AC01 — Daclizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- Globulins
- Immunoglobulins
- Immunologic Factors
- Immunomodulatory Agents
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Interleukin 2 Receptor-directed Antibody Interactions
- Interleukin Inhibitors
- Interleukin-2 Receptor Antagonist
- Interleukin-2 Receptor Blocking Antibody
- Proteins
- 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
- CUJ2MVI71Y
- CAS number
- 152923-56-3
References
- General References
- U.S. Food & Drug Administration: FDA working with manufacturers to withdraw Zinbryta from the market in the United States [Link]
- European Medicines Agency: Public state on Zenapax (daclizumab), Withdrawal of the marketing authorization in the European Union [Link]
- U.S. FDA Zinbryta (daclizumab) Prescribing Information [Link]
- External Links
- UniProt
- P01857
- Genbank
- J00228
- KEGG Drug
- D03639
- PubChem Substance
- 46504469
- 190353
- ChEMBL
- CHEMBL1201605
- Therapeutic Targets Database
- DAP000389
- PharmGKB
- PA164764446
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Daclizumab
- FDA label
- Download (666 KB)
- MSDS
- Download (788 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available End Stage Renal Disease (ESRD) / Living Donors 1 4 Completed Not Available Kidney Transplantation 1 4 Completed Prevention Acute Allograft Rejection in Simultaneous Kidney/Pancreas Transplant Recipients 1 4 Completed Prevention Kidney Diseases / Kidney Failure / Kidney Transplantation 1 4 Completed Prevention Kidney Failure, Kidney Transplant 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous Injection, solution, concentrate Intravenous 25 mg Injection, solution, concentrate Intravenous 25 mg/5mL Liquid Intravenous 5 mg / mL Injection, solution Subcutaneous 150 MG Solution Subcutaneous 150 mg / mL Injection, solution Subcutaneous 150 mg/1mL - Prices
- Not Available
- 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) hydrophobicity -0.437 Not Available isoelectric point 8.46 Not Available
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Interleukin-2 receptor activity
- Specific Function
- Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autorea...
- Gene Name
- IL2RA
- Uniprot ID
- P01589
- Uniprot Name
- Interleukin-2 receptor subunit alpha
- Molecular Weight
- 30818.915 Da
References
- Shamsi TS, Irfan M, Farzana T, Ansari SH, Ahmad G, Shakoor N, Baig MI: Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor antibody Daclizumab for the prevention of acute graft versus host disease in steroid refractory Diamond Blackfan anaemia: a case report. J Pak Med Assoc. 2005 Oct;55(10):454-5. [Article]
- Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I, Lu JG, Gajewski J, Durett A, Cleary K, Champlin R, Andersson BS, Light S: Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000 Jan 1;95(1):83-9. [Article]
- Garcia CD, Bittencourt VB, Tumelero A, Antonello JS, Malheiros D, Garcia VD: Plasmapheresis for recurrent posttransplant focal segmental glomerulosclerosis. Transplant Proc. 2006 Jul-Aug;38(6):1904-5. [Article]
- Krouwels FH, van der Heijden JF, Lutter R, van Neerven RJ, Jansen HM, Out TA: Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. Am J Respir Cell Mol Biol. 1996 Apr;14(4):388-97. [Article]
- Patlolla V, Zhong X, Reed GW, Mandelbrot DA: Efficacy of anti-IL-2 receptor antibodies compared to no induction and to antilymphocyte antibodies in renal transplantation. Am J Transplant. 2007 Jul;7(7):1832-42. [Article]
- Monti P, Brigatti C, Heninger AK, Scirpoli M, Bonifacio E: Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4(+) and CD8(+) T cells. Am J Transplant. 2009 Dec;9(12):2727-35. doi: 10.1111/j.1600-6143.2009.02825.x. Epub 2009 Sep 25. [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
- Yes
- Actions
- Antibody
- General Function
- Interleukin-2 receptor activity
- Specific Function
- Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.
- Gene Name
- IL2RB
- Uniprot ID
- P14784
- Uniprot Name
- Interleukin-2 receptor subunit beta
- Molecular Weight
- 61116.59 Da
References
- Light JA, Sasaki TM, Ghasemian R, Barhyte DY, Fowlkes DL: Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation. Clin Transplant. 2002;16 Suppl 7:30-3. [Article]
- Aguillon JC, Contreras J, Dotte A, Cruzat A, Catalan D, Salazar L, Molina MC, Guerrero J, Lopez M, Soto L, Salazar-Onfray F, Cuchacovich M: [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies]. Rev Med Chil. 2003 Dec;131(12):1445-53. [Article]
- Forrest K, Logan B, Strange J, Roszman TL, Goebel J: Daclizumab therapy in kidney transplantation-different mechanisms of action in- versus ex-vivo? Transpl Immunol. 2005 Mar;14(1):43-7. Epub 2005 Jan 4. [Article]
- Ramos EL, Milford EL, Kirkman RL, Tilney NL, Strom TB, Shapiro ME, Waldmann TA, Wood IG, Rollins MR, Carpenter CB: Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody. Transplantation. 1989 Sep;48(3):415-20. [Article]
- Burkhardt K, Mandel TE, Diamantstein T, Loughnan MS: Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo. Immunology. 1989 Feb;66(2):183-9. [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
- Hoshino S, Oshimi K, Teramura M, Mizoguchi H: Activation via the CD3 and CD16 pathway mediates interleukin-2-dependent autocrine proliferation of granular lymphocytes in patients with granular lymphocyte proliferative disorders. Blood. 1991 Dec 15;78(12):3232-40. [Article]
- Martelletti P, Stirparo G, De Stefano L, Di Sabato F, Giacovazzo M, Rinaldi-Garaci C: Defective expression of IL-2 receptors on peripheral blood lymphocytes from patients with cluster headache. Headache. 1990 Mar;30(4):228-31. [Article]
- Galandrini R, Albi N, Tripodi G, Zarcone D, Terenzi A, Moretta A, Grossi CE, Velardi A: Antibodies to CD44 trigger effector functions of human T cell clones. J Immunol. 1993 May 15;150(10):4225-35. [Article]
- Lanier LL, Kipps TJ, Phillips JH: Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089-106. [Article]
- Hayakawa K, Salmeron MA, Kornbluth J, Bucana C, Itoh K: The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4-dependent versus an IL-2-dependent natural killer cell clone. J Immunol. 1991 Apr 1;146(7):2453-60. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serine-type peptidase activity
- Specific Function
- C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
- Gene Name
- C1R
- Uniprot ID
- P00736
- Uniprot Name
- Complement C1r subcomponent
- Molecular Weight
- 80118.04 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
- Gene Name
- C1QA
- Uniprot ID
- P02745
- Uniprot Name
- Complement C1q subcomponent subunit A
- Molecular Weight
- 26016.47 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
- Gene Name
- C1QB
- Uniprot ID
- P02746
- Uniprot Name
- Complement C1q subcomponent subunit B
- Molecular Weight
- 26721.62 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proe...
- Gene Name
- C1QC
- Uniprot ID
- P02747
- Uniprot Name
- Complement C1q subcomponent subunit C
- Molecular Weight
- 25773.56 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as...
- Gene Name
- FCGR3A
- Uniprot ID
- P08637
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-A
- Molecular Weight
- 29088.895 Da
References
- 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
- Simms HH, Gaither TA, Fries LF, Frank MM: Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function. J Immunol. 1991 Jul 1;147(1):265-72. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized ...
- Gene Name
- FCGR2A
- Uniprot ID
- P12318
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-a
- Molecular Weight
- 35000.42 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complex...
- Gene Name
- FCGR2B
- Uniprot ID
- P31994
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-b
- Molecular Weight
- 34043.355 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulat...
- Gene Name
- FCGR2C
- Uniprot ID
- P31995
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-c
- Molecular Weight
- 35577.96 Da
References
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55