Chemical: Drug
denileukin diftitox

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

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Overview

Generic Names
  • DT
  • Diphtheria toxin precursor
  • NAD(+--diphthamide ADP- ribosyltransferase)
  • denileukin diftitox
Trade Names
  • Ontak
  • Ontak (Seragen Inc)
Brand Mixture Names

PharmGKB Accession Id

PA164750594

Type(s):

Drug

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.

Source: Drug Bank

Indication

For treatment of cutaneous T-cell lymphoma

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Half-Life

70-80 min

Source: Drug Bank

Clearance

Source: Drug Bank

Volume of Distribution

  • 0.06 to 0.09 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C2560H4042N678O799S17

Source: Drug Bank

Average Molecular Weight

57647.3000

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
IL2RA

Drug Targets

Gene Description
IL2RA (source: Drug Bank )
IL2RB (source: Drug Bank )
IL2RG (source: Drug Bank )
No related drugs are available.
No related diseases are available

Publications related to denileukin diftitox: 2

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Denileukin Diftitox (Ontak) as Maintenance Therapy for Peripheral T-Cell Lymphomas: Three Cases with Sustained Remission. Case reports in oncological medicine. 2015. Fuentes Alejandra C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interleukin 2 (IL-2) receptor expression and sensitivity to diphteria fusion toxin DAB389IL-2 in cultured hematopoietic cells. Cancer research. 1996. Re G G, et al. PubMed

LinkOuts

GenBank:
V01536
Web Resource:
Wikipedia
UniProtKB:
P00587
National Drug Code Directory:
62856-603-01
DrugBank:
DB00004
Therapeutic Targets Database:
DAP001098
FDA Drug Label at DailyMed:
42dfffb1-d0f3-42d5-944c-64f092fc436e

Clinical Trials

These are trials that mention denileukin diftitox and are related to either pharmacogenetics or pharmacogenomics.

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NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.