Ibritumomab tiuxetan

Identification

Name
Ibritumomab tiuxetan
Accession Number
DB00078  (BTD00069, BIOD00069)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Indium or yttrium conjugated murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1 heavy chains of 445 amino acids each and two kappa light chains of 213 amino acids each.

Protein structure
Db00078
Protein chemical formula
C6382H9830N1672O1979S54
Protein average weight
143375.5 Da
Sequences
>Ibritumomab tiuxetan heavy chain
QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGAIYPGNGDTSY
NQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYFCARVVYYSNSYWYFDVWGTGTTVTV
SAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDLYT
LSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRGPTIKPCPPCKCPAPNLLGGPSV
FIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQTHREDYNSTL
RVVSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISKPKGSVRAPQVYVLPPPEEEMTK
KQVTLTCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVER
NSYSCSVVHEGLHNHHTTKSFSR
>Ibritumomab tiuxetan light chain
QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYAPSNLASGVPAR
FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGAGTKLELKRADAAPTVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFN
Download FASTA Format
Synonyms
  • Ibritumomab
  • mAb Murine (IGG1) Anti P19437 (CD20_MOUSE)
External IDs
IDEC-129 / IDEC-Y2B8
Product Ingredients
IngredientUNIICASInChI Key
Indium In-111 ibritumomab tiuxetanS9U4ZR2W8VNot AvailableNot applicable
Yttrium y-90 ibritumomab tiuxetanQA846JAV5BNot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZevalinKit1.6 mg/mlIntravenousSpectrum Pharmaceuticals B.V.2004-01-16Not applicableEu
ZevalinKit1.6 mg/1mLSpectrum Pharmaceuticals, Inc.2002-02-19Not applicableUs
ZevalinKit1.6 mg/1mLSpectrum Pharmaceuticals, Inc.2002-02-192009-06-30Us
Categories
UNII
4Q52C550XK
CAS number
206181-63-7

Pharmacology

Indication

For treatment of non-Hodgkin's lymphoma

Associated Conditions
Pharmacodynamics

Ibritumomab is a murine monoclonal antibody against CD20 that has been radiolabeled with yttrium-90.

Mechanism of action

The Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via production of beta particles.

TargetActionsOrganism
AB-lymphocyte antigen CD20
antibody
Human
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHuman
UComplement C1r subcomponentNot AvailableHuman
UComplement C1q subcomponent subunit ANot AvailableHuman
UComplement C1q subcomponent subunit BNot AvailableHuman
UComplement C1q subcomponent subunit CNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHuman
UComplement C1s subcomponentNot AvailableHuman
UHigh affinity immunoglobulin gamma Fc receptor INot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-aNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-bNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-cNot AvailableHuman
Absorption
Not Available
Volume of distribution

Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines)

Protein binding
Not Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to B cells, or by human antimurine antibody production

Route of elimination
Not Available
Half life

0.8 hours (mammalian reticulocytes, in vitro)

Clearance

Approximately 7.2% of injected dose of yttrium Y 90 ibritumomab tiuxetan is excreted in urine within 7 days.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when (R)-warfarin is combined with Ibritumomab tiuxetan.
(R)-warfarinThe risk or severity of bleeding can be increased when (R)-warfarin is combined with Ibritumomab tiuxetan.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when (S)-Warfarin is combined with Ibritumomab tiuxetan.
(S)-WarfarinThe risk or severity of bleeding can be increased when (S)-Warfarin is combined with Ibritumomab tiuxetan.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with 2-Methoxyethanol.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when 4-hydroxycoumarin is combined with Ibritumomab tiuxetan.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Ibritumomab tiuxetan.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Abatacept.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Abciximab is combined with Ibritumomab tiuxetan.
Food Interactions
Not Available

References

General References
  1. Link [Link]
External Links
UniProt
P01865
Genbank
J00470
PubChem Substance
46506112
Therapeutic Targets Database
DAP000383
PharmGKB
PA164781375
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ibritumomab
ATC Codes
V10XX02 — Ibritumomab tiuxetan (90y)
FDA label
Download (102 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBlood and Marrow Transplant (BMT) / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentMalignant Lymphomas1
1, 2TerminatedTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma / Waldenström's Macroglobulinemia (WM)1
1, 2TerminatedTreatmentMalignant Lymphomas1
1, 2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)2
2Active Not RecruitingTreatmentDiffuse Large Cell Lymphoma / Malignant Lymphomas1
2Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas1
2Active Not RecruitingTreatmentMalignant Lymphomas2
2CompletedTreatmentCD20+ Aggressive Non-Hodgkin's Lymphoma / Primary Non-Hodgkin-Lymphoma / Refractory Non-Hodgkin's lymphoma1
2CompletedTreatmentFollicular Lymphoma (FL)2
2CompletedTreatmentLymphoma, B-Cell / Lymphoma, Low-Grade / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)2
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL)1
2CompletedTreatmentLymphoma, Large Cell, Diffuse1
2CompletedTreatmentMalignant Lymphomas2
2CompletedTreatmentMantle Cell Lymphoma (MCL)4
2CompletedTreatmentMarginal Zone Lymphoma1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)3
2RecruitingTreatmentRefractory Non-Hodgkin's lymphoma / Relapsed Non Hodgkin Lymphoma1
2SuspendedTreatmentMalignant Lymphomas1
2TerminatedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2TerminatedTreatmentMalignant Lymphomas1
2TerminatedTreatmentMantle Cell Lymphoma (MCL)1
2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)3
2Unknown StatusTreatmentFollicular Lymphoma (FL)2
2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
2WithdrawnTreatmentAdult Non-Hodgkin's Lymphoma / Anaplastic Large Cell Lymphoma / Lymphoma, AIDS Related1
2WithdrawnTreatmentMalignant Lymphomas1
3Active Not RecruitingTreatmentFollicular Non-Hodgkin's Lymphoma1
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
3TerminatedTreatmentFollicle Center Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
3TerminatedTreatmentFollicular Lymphoma (FL)1
3TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
3WithdrawnTreatmentFollicular Lymphoma (FL) / Lymphoma, Large-Cell, Follicular / Lymphoma, Small Cleaved-Cell, Follicular / Non-Hodgkin's Lymphoma (NHL)1
4CompletedTreatmentLymphoma, Low-Grade / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableCompletedNot AvailableFollicular Lymphoma (FL) / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableCompletedNot AvailableNon-Hodgkin's Lymphoma (NHL)1
Not AvailableCompletedTreatmentMalignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableRecruitingNot AvailableNon-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Spectrum Pharmaceuticals
Dosage forms
FormRouteStrength
Kit1.6 mg/1mL
KitIntravenous1.6 mg/ml
Prices
Unit descriptionCostUnit
Zevalin y-90 kit37800.0USD kit
Zevalin in-111 kit4200.0USD kit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2149329No2008-07-152013-11-12Canada

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.359Not Available
isoelectric point7.91Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antibody
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. Wiseman GA, White CA, Witzig TE, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Grillo-Lopez AJ: Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with zevalin, a 90Y-labeled anti-CD20 monoclonal antibody. Clin Cancer Res. 1999 Oct;5(10 Suppl):3281s-3286s. [PubMed:10541376]
  2. Goldenberg DM: The role of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma: the coming of age of radioimmunotherapy. Crit Rev Oncol Hematol. 2001 Jul-Aug;39(1-2):195-201. [PubMed:11418316]
  3. Dillman RO: Monoclonal antibody therapy for lymphoma: an update. Cancer Pract. 2001 Mar-Apr;9(2):71-80. [PubMed:11879282]
  4. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez AJ, Multani P, White CA: Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [PubMed:12011122]
  5. Witzig TE: Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma. Drugs Today (Barc). 2004 Feb;40(2):111-9. [PubMed:15045033]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Goldsmith SJ: Radioimmunotherapy of lymphoma: Bexxar and Zevalin. Semin Nucl Med. 2010 Mar;40(2):122-35. doi: 10.1053/j.semnuclmed.2009.11.002. [PubMed:20113680]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activat...
Gene Name
C1S
Uniprot ID
P09871
Uniprot Name
Complement C1s subcomponent
Molecular Weight
76683.905 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
Kind
Protein
Organism
Human
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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2018 19:13