Denileukin diftitox

Identification

Name
Denileukin diftitox
Accession Number
DB00004
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.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interleukin-based products / Fusion proteins
Protein Structure
Db00004
Protein Chemical Formula
C2560H4042N678O799S17
Protein Average Weight
57647.3 Da
Sequences
>DB00004 sequence
MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNK
YDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVG
TEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMY
EYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVS
EEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEK
TTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYN
FVESIINLFQVVHNSYNRPAYSPGHKTHAPTSSSTKKTQLQLEHLLLDLQMILNGINNYK
NPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVI
VLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT
Download FASTA Format
Synonyms
  • Denileukin
  • Interleukin-2/diptheria toxin fusion protein
External IDs
  • DAB-389IL2
  • DAB389 IL2
  • DAB389IL2
  • LY-335348
  • LY335348

Pharmacology

Indication

For treatment of cutaneous T-cell lymphoma

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Denileukin 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 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.

TargetActionsOrganism
AInterleukin-2 receptor subunit alpha
binder
Humans
AInterleukin-2 receptor subunit beta
agonist
Humans
UCytokine receptor common subunit gammaNot AvailableHumans
Absorption
Not Available
Volume of distribution
  • 0.06 to 0.09 L/kg
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

70-80 min

Clearance
  • 0.6 - 2.0 mL/min/kg [Lymphoma]
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Darbepoetin alfaThe risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Denileukin diftitox.
ErythropoietinThe risk or severity of Thrombosis can be increased when Erythropoietin is combined with Denileukin diftitox.
Methoxy polyethylene glycol-epoetin betaThe risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Denileukin diftitox.
PeginesatideThe risk or severity of Thrombosis can be increased when Peginesatide is combined with Denileukin diftitox.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OntakInjection, solution150 ug/1mLIntravenousEisai Limited2013-11-012013-11-01US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
L01XX29 — Denileukin diftitox
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
25E79B5CTM
CAS number
173146-27-5

References

General References
  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:17187516]
  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:17454642]
UniProt
P00587
Genbank
V01536
PubChem Substance
46506950
RxNav
214470
ChEMBL
CHEMBL1201550
Therapeutic Targets Database
DAP001098
PharmGKB
PA164750594
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Denileukin_diftitox
FDA label
Download (434 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentLymphoma, T-Cell, Cutaneous1
4CompletedTreatmentLymphoma, T-Cell, Cutaneous / Mycosis Fungoides (MF) / Sezary Syndrome2
2Active Not RecruitingTreatmentMelanoma1
2CompletedSupportive CareDrug/Agent Toxicity by Tissue/Organ / Malignant Lymphomas1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2CompletedTreatmentExtraovarian Peritoneal Cancer / Fallopian Tube Carcinoma / Ovarian Epithelial Cancer1
2CompletedTreatmentGraft Versus Host Disease (GVHD) / Immune System Disorders1
2CompletedTreatmentLeukemias1
2CompletedTreatmentLeukemias / Systemic Mastocytosis1
2CompletedTreatmentLymphoma, B-Cell1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Eisai Inc.
  • Hollister-Stier Laboratories LLC
  • Ligand Pharmaceuticals Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous150 ug/1mL
Prices
Unit descriptionCostUnit
Ontak 150 mcg/ml vial878.4USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.301Not Available
isoelectric point5.45Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Interleukin-2 receptor activity
Specific Function
Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autorea...
Gene Name
IL2RA
Uniprot ID
P01589
Uniprot Name
Interleukin-2 receptor subunit alpha
Molecular Weight
30818.915 Da
References
  1. 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:2786749]
  2. 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:3124610]
  3. Duvic M, Talpur R: Optimizing denileukin diftitox (Ontak) therapy. Future Oncol. 2008 Aug;4(4):457-69. doi: 10.2217/14796694.4.4.457. [PubMed:18684057]
  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:17187516]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Interleukin-2 receptor activity
Specific Function
Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.
Gene Name
IL2RB
Uniprot ID
P14784
Uniprot Name
Interleukin-2 receptor subunit beta
Molecular Weight
61116.59 Da
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:15811959]
  2. Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. [PubMed:16516670]
  3. Duvic M, Talpur R: Optimizing denileukin diftitox (Ontak) therapy. Future Oncol. 2008 Aug;4(4):457-69. doi: 10.2217/14796694.4.4.457. [PubMed:18684057]
  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:17187516]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Interleukin-2 binding
Specific Function
Common subunit for the receptors for a variety of interleukins.
Gene Name
IL2RG
Uniprot ID
P31785
Uniprot Name
Cytokine receptor common subunit gamma
Molecular Weight
42286.68 Da
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:15811959]
  2. Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. [PubMed:16516670]
  3. Foss FM: DAB(389)IL-2 (denileukin diftitox, ONTAK): a new fusion protein technology. Clin Lymphoma. 2000 Nov;1 Suppl 1:S27-31. [PubMed:11707860]

Drug created on June 13, 2005 07:24 / Updated on September 03, 2020 18:59

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates