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Identification
NameRituximab
Accession NumberDB00073  (BIOD00014, BTD00014)
Typebiotech
Groupsapproved
Description

Rituxan 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

Protein structureDb00073
Protein chemical formulaC6416H9874N1688O1987S44
Protein average weight143859.7000
Sequences
>Rituximab heavy chain chimeric
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSY
NQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVS
AASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Rituximab light chain chimeric
QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVR
FSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
SynonymLanguageCode
AntiCD20Not AvailableNot Available
Ig gamma-1 chain C regionNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MabTheraRoche
RituxanGenentech Inc
Brand mixturesNot Available
Categories
CAS number174722-31-7
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor treatment of CD20-positive non-Hodgkins lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
PharmacodynamicsRituximab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lympohomas. The antibody leads to selective killing of B-cells.
Mechanism of actionThe Fab regions of rituximab binds to the CD20 antigen on B lymphocytes, while the Fc domain recruits antibodies and complements to mediate cell lysis.
AbsorptionNot Available
Volume of distribution
  • 3.1 L
Protein bindingNot Available
Metabolism

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

Route of eliminationNot Available
Half life0.8 hours (mammalian reticulocytes, in vitro)
Clearance
  • 0.34 L/day [RA patients]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Low affinity immunoglobulin gamma Fc region receptor III-A
Gene symbol: FCGR3A
UniProt: P08637
rs396991 Not AvailableA > CBetter response to drug therapy (compared to allele A)16609067
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Roche
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Rituxan 10 mg/ml Concentrate 10ml Vial708.17USDvial
Rituxan 10 mg/ml vial68.09USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada21493292008-07-152013-11-12
Canada13368261995-08-292012-08-29
United States57361371998-04-072015-04-07
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.414Not Available
isoelectric point8.68Not Available
References
Synthesis ReferenceNot Available
General Reference
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
  6. http://www.google.com/patents/EP2231183A2?cl=en
  7. http://planetorbitrap.com/data/uploads/528fce2e395be.pdf
External Links
ResourceLink
UniProtP01857
GenbankJ00228
PharmGKBPA451261
Drug Product Database2241927
RxListhttp://www.rxlist.com/cgi/generic/ritux.htm
Drugs.comhttp://www.drugs.com/cdi/rituximab.html
WikipediaRituximab
ATC CodesL01XC02
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelshow(401 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Azilsartan medoxomilAzilsartan medoxomil used in combination with rituximab may lead to hypotension.
BetaxololAntihypertensives like betaxolol may enhance the hypotensive effect of rituximab. Consider temporarily withholding antihypertensive medications for 12 hours prior to rituximab infusion to avoid excessive hypotension during or immediately after infusion.
Certolizumab pegolCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
ChlorothiazideAntihypertensives such as chlorothiazide may enhance the hypotensive effect of Rituximab. Consider temporarily withholding antihypertensive medications for 12 hours prior to rituximab infusion to avoid excessive hypotension during or immediately after infusion.
TelmisartanTelmisartan may increase the hypotensive effect of Rituximab. Telmisartan should be withheld prior to and throughout Rituximab administration.
TerazosinAdditive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Terazosin for 12 hours prior to administration of Rituximab.
TofacitinibAvoid combination due to the potential increase in tofacitinib related adverse effects.
TolazamideAdditive hypotensive effects may occur. Consider withholding Tolazamide for 12 hours prior to administration of Rituximab.
TorasemideAdditive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Torasemide for 12 hours prior to administration of Rituximab.
TrandolaprilTrandolapril may incresae the hypotensive effect of Rituximab.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
TrichlormethiazideAdditive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Trichlormethiazide for 12 hours prior to administration of Rituximab.
ValsartanAdditive hypotensive effects may occur. Increased risk of hypotension. Consider withholding Valsartan for 12 hours prior to administration of Rituximab.
VerapamilVerapamil may increase the hypotensive effects of Rituximab. Consider withholding Verapamil therapy for 12 hours prior to Rituximab infusion.
Food InteractionsNot Available

Targets

1. B-lymphocyte antigen CD20

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antibody

Components

Name UniProt ID Details
B-lymphocyte antigen CD20 P11836 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. van Meerten T, Hagenbeek A: CD20-targeted therapy: the next generation of antibodies. Semin Hematol. 2010 Apr;47(2):199-210. Pubmed
  3. Jaglowski SM, Byrd JC: Rituximab in chronic lymphocytic leukemia. Semin Hematol. 2010 Apr;47(2):156-69. Pubmed

2. Low affinity immunoglobulin gamma Fc region receptor III-B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-B O75015 Details

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

3. Complement C1r subcomponent

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1r subcomponent P00736 Details

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
  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

4. Complement C1q subcomponent subunit A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit A P02745 Details

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
  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
  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. Pubmed

5. Complement C1q subcomponent subunit B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit B P02746 Details

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
  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

6. Complement C1q subcomponent subunit C

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit C P02747 Details

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
  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

7. Low affinity immunoglobulin gamma Fc region receptor III-A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-A P08637 Details

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. Pubmed
  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. Pubmed
  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. Pubmed

8. Complement C1s subcomponent

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1s subcomponent P09871 Details

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
  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

9. High affinity immunoglobulin gamma Fc receptor I

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity immunoglobulin gamma Fc receptor I P12314 Details

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
  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

10. Low affinity immunoglobulin gamma Fc region receptor II-a

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-a P12318 Details

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. Pubmed
  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. Pubmed

11. Low affinity immunoglobulin gamma Fc region receptor II-b

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-b P31994 Details

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
  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

12. Low affinity immunoglobulin gamma Fc region receptor II-c

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-c P31995 Details

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
  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

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Drug created on June 13, 2005 07:24 / Updated on January 31, 2014 11:10