173146-27-5

Basic information

• Product Name: denileukin diftitox
• Synonyms: denileukin diftitox;Dab(389)-il-2;Ly 335348;Ontak;Unii-25E79B5ctm
• CAS NO: 173146-27-5
• Molecular Weight: 0
• Mol File: 173146-27-5.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• CAS DataBase Reference: denileukin diftitox(CAS DataBase Reference)
• NIST Chemistry Reference: denileukin diftitox(173146-27-5)
• EPA Substance Registry System: denileukin diftitox(173146-27-5)

Safety Data

• Hazardous Substances Data: 173146-27-5(Hazardous Substances Data)

Usage

Description

Denileukin diftitox, also known as Ontak, is a fusion protein that acts as a targeted therapy for certain types of cancer. It is composed of a diphtheria toxin fragment A fragment B genetically fused to a human interleukin-2 (IL-2) fragment. The IL-2 fragment seeks out activated T-cells through their IL-2 receptor, and after binding, the fusion protein enters the cell by endocytosis, where the toxin kills the cell by inhibiting protein synthesis. Denileukin diftitox is indicated for the treatment of persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the IL-2 receptor.

Uses

Used in Oncology:
Denileukin diftitox is used as a targeted therapy for the treatment of persistent or recurrent cutaneous T-cell lymphoma (CTCL). It specifically targets malignant cells that express the high-affinity IL-2 receptor on their cell surfaces, such as those found in certain leukemias and lymphomas.
Used in Clinical Trials:
Denileukin diftitox is also being investigated for potential use in the treatment of other conditions, including psoriasis, HIV infection, atopic dermatitis, alopecia areata, multiple sclerosis, and inflammatory bowel disease. In a randomized, double-blind, phase III trial in 71 patients with recurrent CTCL, injection for 5 days every three weeks over 8 courses produced a >50% reduction in tumor burden lasting up to 4 months in 30% of patients.
Used in Pharmaceutical Formulation:
Denileukin diftitox is supplied as a frozen solution in water for injection. It should be stored at 10°C or colder and is suggested that the vials be thawed in a refrigerator at 2°C to 8°C for less than 24 hours or at room temperature for 1 to 2 hours. Prepared solutions should be used within 6 hours. The drug is administered by IV infusion from a bag or through a syringe pump.

Indications

Denileukin diftitox (DAB389 IL-2, Ontak) is indicated for treatment of patients with cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor. Denileukin diftitox is a recombinant fusion protein composed of IL-2 amino acid sequences joined to sequences of diphtheria toxin. The drug targets and destroys cells expressing the highaffinity (CD25/CD122/CD132) IL-2 receptor, including the malignant cells of cutaneous T-cell lymphoma.

Pharmacology

The half-life of the drug is approximately 75 minutes after intravenous infusion. Antibodies directed against the diphtheria domain decrease mean systemic exposure by approximately 75%.Approximately 85% of patients develop such antibodies after a single course of treatment, and nearly all do after 3 cycles.

Clinical Use

rDNA-derived fusion protein consisting of diphtheria toxin fragments A and B as well as interleukin-2. Used in treating cutaneous T-cell lymphoma.

Side effects

Most patients using denileukin diftitox have flulike symptoms (fever, chills, myalgias, nausea, diarrhea) within a few hours to days of treatment. Another common adverse effect is an immediate hypersensitivity syndrome in which hypotension, back pain, dyspnea, chest pain or tightness, and rash may occur. Other notable side effects include a vascular leak syndrome (edema, hypoalbuminemia, hypotension), infections, and elevations of transaminases.