DT-Web

DB00111 - Daclizumab


Identification
Name Daclizumab
Accession Number DB00111 (BIOD00007, BTD00007)
Type biotech
Description 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 142612.1000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Zenapax is a humanized monoclonal antibody used for prevention of renal transplant 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.
Absorption Not Available
Protein binding Not Available
Biotransformation Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes.
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available

Targets


Interleukin-2 receptor alpha chain
Name Interleukin-2 receptor alpha chain
Gene Name IL2RA
Pharmacological action yes
Actions antibody
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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. Epub 2009 Sep 25. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.7692
Interleukin-2 receptor subunit beta
Name Interleukin-2 receptor subunit beta
Gene Name IL2RB
Pharmacological action yes
Actions antibody
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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.7692
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
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
DTHybrid score 1.547
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 1.4548
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
DTHybrid score 1.472
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 1.4729
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 1.4729
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
  • 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 1.5466
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
  • 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. - Pubmed
DTHybrid score 1.6343
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
  • 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 1.5553
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 1.551
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 1.5609

Predictions


Id Partner name Gene Name Score
2782 Complement C1s subcomponent C1S 0.824
3823 Cytokine receptor common gamma chain IL2RG 0.4484
75 B-lymphocyte antigen CD20 MS4A1 0.3345
844 Epidermal growth factor receptor EGFR 0.1518
93 CAMPATH-1 antigen CD52 0.1474
777 Tumor necrosis factor TNF 0.1474
757 Fusion glycoprotein F0 F 0.147
4875 Fusion glycoprotein F0 F 0.147
744 Myeloid cell surface antigen CD33 CD33 0.1349
793 T-cell surface antigen CD2 CD2 0.1302
1783 Intercellular adhesion molecule 1 ICAM1 0.1174
647 Integrin alpha-4 ITGA4 0.1173
1733 Vitronectin VTN 0.1155
572 Integrin alpha-L ITGAL 0.1081
5901 T-cell surface glycoprotein CD3 zeta chain CD247 0.108
1789 Lymphotoxin-alpha LTA 0.108
302 T-cell surface glycoprotein CD3 epsilon chain CD3E 0.108
5900 T-cell surface glycoprotein CD3 gamma chain CD3G 0.108
5899 T-cell surface glycoprotein CD3 delta chain CD3D 0.108
1269 Tumor necrosis factor receptor superfamily member 1B TNFRSF1B 0.1079
290 Prostaglandin G/H synthase 2 PTGS2 0.1054
955 Complement C5 C5 0.1033
5898 Complement C3 C3 0.103
2039 Integrin beta-3 ITGB3 0.1005
488 Integrin alpha-IIb ITGA2B 0.1004
183 Vascular endothelial growth factor A VEGFA 0.0927
723 Cytosolic phospholipase A2 PLA2G4A 0.0854
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.0836
3947 Xanthine dehydrogenase/oxidase XDH 0.075
554 Low-density lipoprotein receptor LDLR 0.0664
3811 Cytochrome P450 19A1 CYP19A1 0.0545
6013 Cytochrome P450 2E1 CYP2E1 0.0536
4512 Cytochrome P450 3A4 CYP3A4 0.04
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
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