Rituximab (T3D2671)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (12)XML
Targets (12)
Record Information
Version2.0
Creation Date2009-07-15 20:45:27 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2671
Identification
Common NameRituximab
ClassProtein
DescriptionRituxan is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences. Rituximab is composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids
Compound Type
  • Amide
  • Amine
  • Animal Toxin
  • Antineoplastic Agent
  • Antirheumatic Agent
  • Immunologic Factor
  • Organic Compound
  • Protein
  • Synthetic Compound
Protein StructureT3d2671
Synonyms
Synonym
AntiCD20
Ig gamma-1 chain C region
MabThera
Rituxan
Chemical FormulaNot Available
Average Molecular Mass36105.695 g/mol
CAS Registry Number174722-31-7
Sequence
>lcl|BSEQ0005514|Ig gamma-1 chain C region
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE
LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Chemical Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution (1).
Experimental Properties
PropertyValue
Melting Point61°C (FAB fragment), 71°C (whole mAb)
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Toxicity Profile
Route of ExposureIntravenous
Mechanism of ToxicityBinds to the CD20 antigen which is found on mature B lymphocytes. The Fc domain recruits immune effector functions to mediate B-cell lysis. The antibody appears to induce apoptosis, antibody mediated cytotoxicity and complement-dependent cytotoxicity.
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases. Half Life: 0.8 hours (mammalian reticulocytes, in vitro)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor treatment of CD20-positive non-Hodgkins lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
Minimum Risk LevelNot Available
Health EffectsRituxan may cause hepatitis B virus reactivation, stomach, bowel and heart problems, increase the chances for getting infections. Other health effects may include progressive multifocal leukoencephalopathy, infusion reactions, tumor lysis syndrome , and severe skin reactions (RxList A308, A328).
SymptomsNot Available
TreatmentSignificant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. (10)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00073
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDCHEMBL1201576
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDP01857
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB ID1AJ7
ACToR IDNot Available
Wikipedia LinkRituximab
References
Synthesis ReferenceNot Available
MSDST3D2671.pdf
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Ram R, Bonstein L, Gafter-Gvili A, Ben-Bassat I, Shpilberg O, Raanani P: Rituximab-associated acute thrombocytopenia: an under-diagnosed phenomenon. Am J Hematol. 2009 Apr;84(4):247-50. doi: 10.1002/ajh.21372. [19260124 ]
  3. McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK: Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. [9704735 ]
  4. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T: Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81. [15201414 ]
  5. Braendstrup P, Bjerrum OW, Nielsen OJ, Jensen BA, Clausen NT, Hansen PB, Andersen I, Schmidt K, Andersen TM, Peterslund NA, Birgens HS, Plesner T, Pedersen BB, Hasselbalch HC: Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. Am J Hematol. 2005 Apr;78(4):275-80. [15795920 ]
  6. Binder M, Otto F, Mertelsmann R, Veelken H, Trepel M: The epitope recognized by rituximab. Blood. 2006 Sep 15;108(6):1975-8. Epub 2006 May 16. [16705086 ]
  7. Burton C, Kaczmarski R, Jan-Mohamed R: Interstitial pneumonitis related to rituximab therapy. N Engl J Med. 2003 Jun 26;348(26):2690-1; discussion 2690-1. [12826649 ]
  8. http://www.google.com/patents/EP2231183A2?cl=en
  9. http://planetorbitrap.com/data/uploads/528fce2e395be.pdf
  10. Wikipedia. Tramadol. Last Updated 8 August 2009. [Link]
  11. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Low affinity immunoglobulin gamma Fc region receptor III-B
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 cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils.
Gene Name:
FCGR3B
Uniprot ID:
O75015
Molecular Weight:
26215.64 Da
References
  1. Treon SP, Hansen M, Branagan AR, Verselis S, Emmanouilides C, Kimby E, Frankel SR, Touroutoglou N, Turnbull B, Anderson KC, Maloney DG, Fox EA: Polymorphisms in FcgammaRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstrom's macroglobulinemia. J Clin Oncol. 2005 Jan 20;23(3):474-81. [15659493 ]
  2. Bowles JA, Weiner GJ: CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells. J Immunol Methods. 2005 Sep;304(1-2):88-99. [16109421 ]
  3. Bowles JA, Wang SY, Link BK, Allan B, Beuerlein G, Campbell MA, Marquis D, Ondek B, Wooldridge JE, Smith BJ, Breitmeyer JB, Weiner GJ: Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab. Blood. 2006 Oct 15;108(8):2648-54. Epub 2006 Jul 6. [16825493 ]
  4. Hatjiharissi E, Xu L, Santos DD, Hunter ZR, Ciccarelli BT, Verselis S, Modica M, Cao Y, Manning RJ, Leleu X, Dimmock EA, Kortsaris A, Mitsiades C, Anderson KC, Fox EA, Treon SP: Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the Fc{gamma}RIIIa-158 V/V and V/F polymorphism. Blood. 2007 Oct 1;110(7):2561-4. Epub 2007 May 2. [17475906 ]
Target Details
2. Complement C1q subcomponent subunit A
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) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QA
Uniprot ID:
P02745
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. [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. [17016423 ]
  3. Di Gaetano N, Cittera E, Nota R, Vecchi A, Grieco V, Scanziani E, Botto M, Introna M, Golay J: Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol. 2003 Aug 1;171(3):1581-7. [12874252 ]
Target Details
3. Low affinity immunoglobulin gamma Fc region receptor III-A
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 phagocytosis.
Gene Name:
FCGR3A
Uniprot ID:
P08637
Molecular Weight:
29088.895 Da
References
  1. Niwa R, Hatanaka S, Shoji-Hosaka E, Sakurada M, Kobayashi Y, Uehara A, Yokoi H, Nakamura K, Shitara K: Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 Is independent of FcgammaRIIIa functional polymorphism. Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6248-55. [15448014 ]
  2. Hatjiharissi E, Hansen M, Santos DD, Xu L, Leleu X, Dimmock EW, Ho AW, Hunter ZR, Branagan AR, Patterson CJ, Kortsaris A, Verselis S, Fox E, Treon SP: Genetic linkage of Fc gamma RIIa and Fc gamma RIIIa and implications for their use in predicting clinical responses to CD20-directed monoclonal antibody therapy. Clin Lymphoma Myeloma. 2007 Jan;7(4):286-90. [17324336 ]
  3. Kim DH, Jung HD, Kim JG, Lee JJ, Yang DH, Park YH, Do YR, Shin HJ, Kim MK, Hyun MS, Sohn SK: FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood. 2006 Oct 15;108(8):2720-5. Epub 2006 Apr 11. [16609067 ]
Target Details
4. Complement C1q subcomponent subunit B
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) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QB
Uniprot ID:
P02746
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. [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. [17016423 ]
Target Details
5. Complement C1q subcomponent subunit C
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) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QC
Uniprot ID:
P02747
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. [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. [17016423 ]
Target Details
6. Complement C1r subcomponent
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
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. [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. [17016423 ]
Target Details
7. Complement C1s subcomponent
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, activate C2 and C4.
Gene Name:
C1S
Uniprot ID:
P09871
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. [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. [17016423 ]
Target Details
8. High affinity immunoglobulin gamma Fc receptor I
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
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. [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. [17016423 ]
Target Details
9. Low affinity immunoglobulin gamma Fc region receptor II-a
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 antigens.
Gene Name:
FCGR2A
Uniprot ID:
P12318
Molecular Weight:
35000.42 Da
References
  1. Hatjiharissi E, Hansen M, Santos DD, Xu L, Leleu X, Dimmock EW, Ho AW, Hunter ZR, Branagan AR, Patterson CJ, Kortsaris A, Verselis S, Fox E, Treon SP: Genetic linkage of Fc gamma RIIa and Fc gamma RIIIa and implications for their use in predicting clinical responses to CD20-directed monoclonal antibody therapy. Clin Lymphoma Myeloma. 2007 Jan;7(4):286-90. [17324336 ]
  2. Kim DH, Jung HD, Kim JG, Lee JJ, Yang DH, Park YH, Do YR, Shin HJ, Kim MK, Hyun MS, Sohn SK: FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood. 2006 Oct 15;108(8):2720-5. Epub 2006 Apr 11. [16609067 ]
Target Details
10. Low affinity immunoglobulin gamma Fc region receptor II-b
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 complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.
Gene Name:
FCGR2B
Uniprot ID:
P31994
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. [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. [17016423 ]
Target Details
11. Low affinity immunoglobulin gamma Fc region receptor II-c
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 modulation of antibody production by B-cells.
Gene Name:
FCGR2C
Uniprot ID:
P31995
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. [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. [17016423 ]
Target Details
12. B-lymphocyte antigen CD20
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
Molecular Weight:
33076.99 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]