Denileukindiftitox
- CAS Number: 173146-27-5
Denileukindiftitox, also known as DAB ( 389) IL- 2 indicates, is the international non-proprietary name for an approved in the United States immunotoxin for the treatment of patients with refractory cutaneous T - cell lymphoma.
Description
Denileukindiftitox is a recombinant, that is genetically produced in cultures of Escherichia coli cytotoxic chimeric fusion protein. It consists of an interleukin -2 peptide sequence was fused with the diphtheria toxin. Interleukin -2 binds to the interleukin 2 receptor, which is expressed mainly on T cells - as well as the malignant T-lymphocytes. After binding to the receptor, the immunotoxin from the cell by receptor-mediated endocytosis is internalisert. In the endosome, the immunotoxin is proteolytically cleaved, thereby releasing the catalytically active A- fragment of the toxin. The enzymatic domain of the toxin (the A fragment) catalyzes the modification of diphthamide, an amino acid formed from histidine, by transfer of an ADP -ribose moiety from NAD by elimination of nicotinamide on the Diphtamid (ADP- ribosylation ). The elongation factor 2 (EF -2 ), an enzyme that catalyzes the translation during protein synthesis containing diphthamide. By the modification of the EF-2 Diphthamids is inhibited in its ability to translation and the protein synthesis in the cell is interrupted, which ultimately leads to the death of the cell.
Denileukindiftitox was approved in the United States as the first immunotoxin by the FDA in 1999. In Europe, however, it is not allowed. Several clinical trials for other indications, for example, against mycosis fungoides and malignant melanoma are underway.
Denileukindiftitox is administered intravenously. The side effects are in some cases considerably. Nausea, vomiting, diarrhea, fatigue, difficulty breathing, fever, cough, pruritus, and peripheral edema are observed in over 20 percent of patients. More than 10 percent, the vascular leak syndrome is observed. There is evidence that administration of Denileukindiftitox can lead to a loss of vision.
Denileukindiftitox has the following protein sequence ( in single letter code ):
Trade name
Denileukindiftitox is marketed in the U.S. under the brand name Ontak.