denileukin diftitox

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Ligands
denileukin diftitox

GtoPdb Ligand ID: 7044

Synonyms: DAB389 IL2 | LY 335348 | Ontak®

denileukin diftitox is an approved drug (FDA (1999))

Compound class: Peptide or derivative

Comment: Denileukin diftitox is an anti-cancer drug. The drug is a recombinant protein containing peptide sequences of both interleukin-2 and diphtheria toxin [1,3].

No information available.

No information available.

Summary of Clinical Use
Denileukin diftitox is used to destroy malignant leukemia and lymphoma cells which express cell surface IL-2 receptors.

Summary of Clinical Use

Denileukin diftitox is used to destroy malignant leukemia and lymphoma cells which express cell surface IL-2 receptors.

Mechanism Of Action and Pharmacodynamic Effects
The IL-2 sequence of this dual domain drug binds to cell surface IL-2 receptors and upon internalisation via receptor-mediated endocytosis and endocytic processing, the diptheria toxin is liberated and is able to act on its intracellular target, EEF2 (eukaryotic translation elongation factor 2) [1], effectively shutting down protein synthesis in the cell. Diptheria toxin belongs to a diphthamide-specific class of ADP-ribose transferases, and is able to inactvate EEF2 by catalysing the transfer of NAD⁺ to the diphthamide residue (a posttranslationally modified histidine residue, PubChem CID 6438375) contained in this protein. Mutation of this dipthamide resudue renders EEF2 resistant to diptheria toxin [2].

Mechanism Of Action and Pharmacodynamic Effects

The IL-2 sequence of this dual domain drug binds to cell surface IL-2 receptors and upon internalisation via receptor-mediated endocytosis and endocytic processing, the diptheria toxin is liberated and is able to act on its intracellular target, EEF2 (eukaryotic translation elongation factor 2) [1], effectively shutting down protein synthesis in the cell. Diptheria toxin belongs to a diphthamide-specific class of ADP-ribose transferases, and is able to inactvate EEF2 by catalysing the transfer of NAD⁺ to the diphthamide residue (a posttranslationally modified histidine residue, PubChem CID 6438375) contained in this protein. Mutation of this dipthamide resudue renders EEF2 resistant to diptheria toxin [2].