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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
- 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.
Target Actions Organism AInterleukin-2 receptor subunit alpha binderHumans AInterleukin-2 receptor subunit beta agonistHumans UCytokine receptor common subunit gamma Not Available Humans - 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.
Drug Interaction Unlock Additional DataDarbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Denileukin diftitox. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Denileukin diftitox. Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Denileukin diftitox. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Denileukin diftitox. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
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
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataOntak Injection, solution 150 ug/1mL Intravenous Eisai Limited 2013-11-01 2013-11-01 US 
Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
Categories
- ATC Codes
- L01XX29 — Denileukin diftitox
- Drug Categories
- ADP Ribose Transferases
- Amino Acids, Peptides, and Proteins
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Bacterial Toxins
- Biological Factors
- CD25-directed Cytotoxin
- Cytokines
- Enzymes
- Enzymes and Coenzymes
- Glycosyltransferases
- Intercellular Signaling Peptides and Proteins
- Interleukins
- Lymphokines
- Narrow Therapeutic Index Drugs
- Pentosyltransferases
- Peptides
- Proteins
- Recombinant Proteins
- Toxins, Biological
- Transferases
- 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
- 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]
- 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]
- External Links
- UniProt
- P00587
- Genbank
- V01536
- PubChem Substance
- 46506950
- 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
Phase Status Purpose Conditions Count 4 Completed Treatment Lymphoma, T-Cell, Cutaneous 1 4 Completed Treatment Lymphoma, T-Cell, Cutaneous / Mycosis Fungoides (MF) / Sezary Syndrome 2 2 Active Not Recruiting Treatment Melanoma 1 2 Completed Supportive Care Drug/Agent Toxicity by Tissue/Organ / Malignant Lymphomas 1 2 Completed Treatment Chronic Lymphocytic Leukaemia (CLL) 1 2 Completed Treatment Extraovarian Peritoneal Cancer / Fallopian Tube Carcinoma / Ovarian Epithelial Cancer 1 2 Completed Treatment Graft Versus Host Disease (GVHD) / Immune System Disorders 1 2 Completed Treatment Leukemias 1 2 Completed Treatment Leukemias / Systemic Mastocytosis 1 2 Completed Treatment Lymphoma, B-Cell 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Eisai Inc.
- Hollister-Stier Laboratories LLC
- Ligand Pharmaceuticals Inc.
- Dosage Forms
Form Route Strength Injection, solution Intravenous 150 ug/1mL - Prices
Unit description Cost Unit Ontak 150 mcg/ml vial 878.4USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source hydrophobicity -0.301 Not Available isoelectric point 5.45 Not 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
- 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]
- 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]
- 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]
- 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
- 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]
- Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. [PubMed:16516670]
- 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]
- 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]
- 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
- 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]
- Foss F: Clinical experience with denileukin diftitox (ONTAK). Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6. [PubMed:16516670]
- 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
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