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| Primary information |
|---|
| ID | 10025 |
| Therapeutic ID | Th1004 |
| Protein Name | Denileukin diftitox |
| Sequence | >Th1004_Denileukin_diftitox
MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTHAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT
|
| Molecular Weight | 57647.3 |
| Chemical Formula | C2560H4042N678O799S17 |
| Isoelectric Point | 5.45 |
| Hydrophobicity | -0.301 |
| Melting point | NA |
| Half-life | 1.16-1.3 hours |
| Description | A recombinant (using E. coli expression system) DNA-derived cytotoxic protein containing amino acid sequences for diphtheria toxin fragments A and B (Met 1-Thr 387)-His and sequences for interleukin-2 (Ala 1-Thr 133). |
| Indication/Disease | Used in the treatment of cutaneous T-cell lymphoma. |
| Pharmacodynamics | Denileukin diftitox (Ontak) uses the cytocidal action of diphtheria toxin on cells which express the IL-2 receptor. The human IL-2 receptor exists in three forms on basis of affinity, low (CD25), intermediate (CD122/CD132) and high (CD25/CD122/CD132). 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. The IL-2 receptor (Tac) subunit is expressed on activated lymphocytes. The diphtheria toxin associated with Ontak selectively kills the IL-2 bearing cells. |
| Toxicity | NA |
| Metabolism | NA |
| Absorption | NA |
| 0.06 to 0.09 L/kg |
| Clearance | 0.6 - 2.0 mL/min/kg [Lymphoma] |
| Categories | ADP Ribose Transferases, Amino Acids, Peptides, and Proteins, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Bacterial Toxins, Biological Factors, Cancer immunotherapy, CD25-directed Cytotoxin, Cytokines, Enzymes, Enzymes and Coenzymes, Glycosyltransferases, Immunotherapy, Intercellular Signaling Peptides and Proteins, Interleukins, Lymphokines, Narrow Therapeutic Index Drugs, Pentosyltransferases, Peptides, Proteins, Recombinant Proteins, Toxins, Biological, Transferases |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | Rilonacept decreases effects of toxoids by pharmacodynamic antagonism |
| Target | Interleukin-2 receptor subunit alpha,Interleukin-2 receptor subunit beta,Cytokine receptor common subunit gamma |
| Brand Name | Ontak |
| Company | Eisai Inc. , Hollister-Stier Laboratories LLC , Ligand Pharmaceuticals Inc. |
| Brand Description | Eisai Inc. , Hollister-Stier Laboratories LLC , Ligand Pharmaceuticals Inc. |
| Prescribed For | Treating leukemia and lymphomas, including cutaneous (of the skin) T-cell lymphoma. |
| Chemical Name | NA |
| Formulation | Ontak contains 300 mcg of recombinant denileukin diftitox in a sterile solution of citric acid (20 mM), EDTA (0.05 mM) and polysorbate 20 ( < 1%) in Water for Injection, USP. The solution has a pH range of 6.9-7.2. |
| Physical Appearance | Sterile, white, preservative-free, lyophilized powder. |
| Route of Administration | Intravenous (Intravenous) administration |
| Recommended Dosage | NA |
| Contraindication | allergic |
| Side Effects | Common side effects include:headache, dizziness, or nervousness, numbness or tingling, skin itching or rash, runny or stuffy nose; weight gain or loss; mild diarrhea or constipation, or nausea, vomiting, loss of appetite. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |