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Identification
NameDenileukin diftitox
Accession NumberDB00004  (BIOD00084, BTD00084)
Typebiotech
Groupsapproved, investigational
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.

Protein structureDb00004
Protein chemical formulaC2560H4042N678O799S17
Protein average weight57647.3000
Sequences
>DB00004 sequence
MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNK
YDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVG
TEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMY
EYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVS
EEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEK
TTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYN
FVESIINLFQVVHNSYNRPAYSPGHKTHAPTSSSTKKTQLQLEHLLLDLQMILNGINNYK
NPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVI
VLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT
Download FASTA Format
Synonyms
SynonymLanguageCode
Diphtheria toxin precursorNot AvailableNot Available
DTNot AvailableNot Available
NAD(+--diphthamide ADP- ribosyltransferase)Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
OntakSeragen Inc
Brand mixturesNot Available
Categories
CAS number173146-27-5
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 cutaneous T-cell lymphoma
PharmacodynamicsDenileukin diftitox (Ontak) directs the cytocidal action of diphtheria toxin to cells which express the IL-2 receptor. The human IL-2 receptor exists in three forms, low (CD25), intermediate (CD122/CD132) and high (CD25/CD122/CD132) affinity. Malignant cells expressing one or more of the subunits of the IL-2 receptor are found in certain leukemias and lymphomas including cutaneous T-cell lymphoma (CTCL). Ontak interacts with the high affinity IL-2 receptor on the cell surface and inhibits cellular protein synthesis, resulting in cell death within hours.
Mechanism of actionDenileukin 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.
AbsorptionNot Available
Volume of distribution
  • 0.06 to 0.09 L/kg
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life70-80 min
Clearance
  • 0.6 – 2.0 mL/min/kg [Lymphoma]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Ontak 150 mcg/ml vial878.4USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.301Not Available
isoelectric point5.45Not Available
References
Synthesis ReferenceNot Available
General Reference
  1. 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
  2. Park M, Liu GT, Piltz-Seymour J, Wisda CL, Rook AH, Junkins-Hopkins JM, Nasta SD, Kim EJ: Vision loss following denileukin diftitox treatment: a case report of possible posterior ischemic optic neuropathy. Leuk Lymphoma. 2007 Apr;48(4):808-11. Pubmed
External Links
ResourceLink
UniProtP00587
GenbankV01536
PharmGKBPA164750594
RxListhttp://www.rxlist.com/cgi/generic2/denileukin.htm
Drugs.comhttp://www.drugs.com/cdi/denileukin-diftitox.html
WikipediaDenileukin_diftitox
ATC CodesL01XX29
AHFS CodesNot Available
PDB Entries
FDA labelshow(434 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Rilonaceptdecreases effects of toxoids by pharmacodynamic antagonism.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food InteractionsNot Available

Targets

1. Interleukin-2 receptor subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details
Interleukin-2 receptor subunit alpha P01589 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. 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
  4. 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
  5. Duvic M, Talpur R: Optimizing denileukin diftitox (Ontak) therapy. Future Oncol. 2008 Aug;4(4):457-69. Pubmed
  6. 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
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Interleukin-2 receptor subunit beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Interleukin-2 receptor subunit beta P14784 Details

References:

  1. 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
  2. Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. Pubmed
  3. Duvic M, Talpur R: Optimizing denileukin diftitox (Ontak) therapy. Future Oncol. 2008 Aug;4(4):457-69. Pubmed
  4. 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
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Cytokine receptor common subunit gamma

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cytokine receptor common subunit gamma P31785 Details

References:

  1. 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
  2. Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. Pubmed
  3. Foss FM: DABIL-2 (denileukin diftitox, ONTAK): a new fusion protein technology. Clin Lymphoma. 2000 Nov;1 Suppl 1:S27-31. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 14, 2014 13:43