DT-Web

DB00073 - Rituximab


Identification
Name Rituximab
Accession Number DB00073 (BIOD00014, BTD00014)
Type biotech
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
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 143859.7000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of CD20-positive non-Hodgkins lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
Mechanism of action The Fab regions of rituximab binds to the CD20 antigen on B lymphocytes, while the Fc domain recruits antibodies and complements to mediate cell lysis.
Absorption Not Available
Protein binding Not Available
Biotransformation Most likely removed by opsonization via the reticuloendothelial system when bound to B lymphocytes, or by human antimurine antibody production
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Azilsartan medoxomil Azilsartan medoxomil used in combination with rituximab may lead to hypotension.
Betaxolol Antihypertensives 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 pegol Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
Chlorothiazide Antihypertensives 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.
Telmisartan Telmisartan may increase the hypotensive effect of Rituximab. Telmisartan should be withheld prior to and throughout Rituximab administration.
Terazosin Additive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Terazosin for 12 hours prior to administration of Rituximab.
Tofacitinib Avoid combination due to the potential increase in tofacitinib related adverse effects.
Tolazamide Additive hypotensive effects may occur. Consider withholding Tolazamide for 12 hours prior to administration of Rituximab.
Torasemide Additive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Torasemide for 12 hours prior to administration of Rituximab.
Trandolapril Trandolapril may incresae the hypotensive effect of Rituximab.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Trichlormethiazide Additive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Trichlormethiazide for 12 hours prior to administration of Rituximab.
Valsartan Additive hypotensive effects may occur. Increased risk of hypotension. Consider withholding Valsartan for 12 hours prior to administration of Rituximab.
Verapamil Verapamil may increase the hypotensive effects of Rituximab. Consider withholding Verapamil therapy for 12 hours prior to Rituximab infusion.
Food Interactions Not Available

Targets


B-lymphocyte antigen CD20
Name B-lymphocyte antigen CD20
Gene Name MS4A1
Pharmacological action yes
Actions antibody
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • van Meerten T, Hagenbeek A: CD20-targeted therapy: the next generation of antibodies. Semin Hematol. 2010 Apr;47(2):199-210. - Pubmed
  • Jaglowski SM, Byrd JC: Rituximab in chronic lymphocytic leukemia. Semin Hematol. 2010 Apr;47(2):156-69. - Pubmed
DTHybrid score 0.5397
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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 1.655
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 1.5628
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
  • 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
DTHybrid score 1.5811
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 1.582
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 1.582
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
  • 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
  • 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
  • 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
DTHybrid score 1.6546
Complement C1s subcomponent
Name Complement C1s subcomponent
Gene Name C1S
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 1.1652
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 1.7397
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
  • 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
  • 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
DTHybrid score 1.6632
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 1.6578
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 1.6689

Predictions


Id Partner name Gene Name Score
724 Interleukin-2 receptor alpha chain IL2RA 0.2111
717 Interleukin-2 receptor subunit beta IL2RB 0.2111
844 Epidermal growth factor receptor EGFR 0.1751
777 Tumor necrosis factor TNF 0.1699
744 Myeloid cell surface antigen CD33 CD33 0.1557
93 CAMPATH-1 antigen CD52 0.1474
757 Fusion glycoprotein F0 F 0.147
4875 Fusion glycoprotein F0 F 0.147
1733 Vitronectin VTN 0.1334
793 T-cell surface antigen CD2 CD2 0.1302
5901 T-cell surface glycoprotein CD3 zeta chain CD247 0.1247
1789 Lymphotoxin-alpha LTA 0.1247
302 T-cell surface glycoprotein CD3 epsilon chain CD3E 0.1247
5900 T-cell surface glycoprotein CD3 gamma chain CD3G 0.1247
5899 T-cell surface glycoprotein CD3 delta chain CD3D 0.1246
1269 Tumor necrosis factor receptor superfamily member 1B TNFRSF1B 0.1246
1783 Intercellular adhesion molecule 1 ICAM1 0.1174
647 Integrin alpha-4 ITGA4 0.1173
488 Integrin alpha-IIb ITGA2B 0.1156
2039 Integrin beta-3 ITGB3 0.1139
572 Integrin alpha-L ITGAL 0.1081
955 Complement C5 C5 0.1033
5898 Complement C3 C3 0.103
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.0964
183 Vascular endothelial growth factor A VEGFA 0.0927
554 Low-density lipoprotein receptor LDLR 0.0664
3811 Cytochrome P450 19A1 CYP19A1 0.0627
290 Prostaglandin G/H synthase 2 PTGS2 0.0526
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
309 Antithrombin-III SERPINC1 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
↑