DT-Web

DB00004 - Denileukin diftitox


Identification
Name Denileukin diftitox
Accession Number DB00004 (BIOD00084, BTD00084)
Type biotech
Description A recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met 1-Thr 387)-His followed by the sequences for interleukin-2 (IL-2; Ala 1-Thr 133). It is produced in an E. coli expression system.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 57647.3000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of cutaneous T-cell lymphoma
Mechanism of action Denileukin diftitox binds to the high-affinity IL-2 receptor complex. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes. The diphtheria toxin associated with Ontak then selectively kills the IL-2 bearing cells.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Rilonacept decreases effects of toxoids by pharmacodynamic antagonism.
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 binder
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
  • Kiyokawa T, Shirono K, Hattori T, Nishimura H, Yamaguchi K, Nichols JC, Strom TB, Murphy JR, Takatsuki K: Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia. Cancer Res. 1989 Jul 15;49(14):4042-6. - Pubmed
  • Murphy JR, Kelley VE, Strom TB: Interleukin 2 toxin: a step toward selective immunomodulation. Am J Kidney Dis. 1988 Feb;11(2):159-62. - Pubmed
  • Duvic M, Talpur R: Optimizing denileukin diftitox (Ontak) therapy. Future Oncol. 2008 Aug;4(4):457-69. - Pubmed
  • Turturro F: Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders. Expert Rev Anticancer Ther. 2007 Jan;7(1):11-7. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.9126
Interleukin-2 receptor subunit beta
Name Interleukin-2 receptor subunit beta
Gene Name IL2RB
Pharmacological action yes
Actions agonist
References
  • Foss F, Demierre MF, DiVenuti G: A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2005 Jul 15;106(2):454-7. Epub 2005 Apr 5. - Pubmed
  • Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. - Pubmed
  • Duvic M, Talpur R: Optimizing denileukin diftitox (Ontak) therapy. Future Oncol. 2008 Aug;4(4):457-69. - Pubmed
  • Turturro F: Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders. Expert Rev Anticancer Ther. 2007 Jan;7(1):11-7. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.9124
Cytokine receptor common gamma chain
Name Cytokine receptor common gamma chain
Gene Name IL2RG
Pharmacological action unknown
Actions Not Available
References
  • Foss F, Demierre MF, DiVenuti G: A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2005 Jul 15;106(2):454-7. Epub 2005 Apr 5. - Pubmed
  • Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. - Pubmed
  • Foss FM: DAB(389)IL-2 (denileukin diftitox, ONTAK): a new fusion protein technology. Clin Lymphoma. 2000 Nov;1 Suppl 1:S27-31. - Pubmed
DTHybrid score 0.9067

Predictions


Id Partner name Gene Name Score
723 Cytosolic phospholipase A2 PLA2G4A 0.1598
3947 Xanthine dehydrogenase/oxidase XDH 0.1402
290 Prostaglandin G/H synthase 2 PTGS2 0.1117
3817 Complement C1q subcomponent subunit C C1QC 0.1011
3816 Complement C1q subcomponent subunit B C1QB 0.1011
3815 Complement C1q subcomponent subunit A C1QA 0.101
6013 Cytochrome P450 2E1 CYP2E1 0.1002
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.1
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.1
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.1
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0999
3814 Complement C1r subcomponent C1R 0.0999
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.099
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.098
4512 Cytochrome P450 3A4 CYP3A4 0.0748
2782 Complement C1s subcomponent C1S 0.0535
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