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| Primary information |
|---|
| ID | 10257 |
| Therapeutic ID | Th1036 |
| Protein Name | Aldesleukin |
| Sequence | >Th1036_Aldesleukin
MPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQSIISTLT
|
| Molecular Weight | 15314.8 |
| Chemical Formula | C690H1115N177O202S6 |
| Isoelectric Point | 7.31 |
| Hydrophobicity | -0.192 |
| Melting point | NA |
| Half-life | 0.22-1.42 hours |
| Description | Aldesleukin, a lymphokine, is produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. Genetic engineering techniques were used to modify the human IL-2 gene, and the resulting expression clone encodes a modified human interleukin-2. This recombinant form differs from native interleukin-2 in the following ways: a) Aldesleukin is not glycosylated because it is derived from E. coli; b) the molecule has no N-terminal alanine; the codon for this amino acid was deleted during the genetic engineering procedure; c) the molecule has serine substituted for cysteine at amino acid position 125. |
| Indication/Disease | For treatment of adults with metastatic renal cell carcinoma. |
| Pharmacodynamics | Aldesleukin is used to treat renal cell carcinoma, it induces the enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines, the enhancement of lymphocyte cytotoxicity, the induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and the induction of interferon-gamma production. IL-2 is normally produced by the body, secreted by T cells, and stimulates growth and differentiation of T cell response. It can be used in immunotherapy to treat cancer. It enhances the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor. |
| Mechanism of Action | Aldesleukin binds to the IL-2 receptor which leads to heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These events led to the creation of an activated receptor complex, to which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. These events stimulate growth and differentiation of T cells. |
| Toxicity | NA |
| Metabolism | NA |
| Absorption | NA |
| 0.18 l/kg |
| Clearance | The pharmacokinetic profile of Proleukin is characterized by high plasma concentrations following a short IV infusion, rapid distribution into the extravascular space and elimination from the body by metabolism in the kidneys with little or no bioactive p |
| Categories | Adjuvants, Immunologic, Amino Acids, Peptides, and Proteins, Anti-HIV Agents, Anti-Infective Agents, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Biological Factors, Cancer immunotherapy, Cytochrome P-450 CYP2E1 Inhibitors, Cytochrome P-450 CYP2E1 Inhibitors (strength unknown), Cytochrome P-450 CYP3A Inhibitors, Cytochrome P-450 CYP3A4 Inhibitors, Cytochrome P-450 CYP3A4 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Cytokines, Drugs that are Mainly Renally Excreted, Hypotensive Agents, Immunosuppressive Agents, Immunotherapy, Increased Lymphocyte Activation, Increased Lymphocyte Cell Production, Intercellular Signaling Peptides and Proteins, Interleukins, Lymphocyte Growth Factor, Lymphokines, Myelosuppressive Agents, Narrow Therapeutic Index Drugs, Peptides, Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | Corticosteroids such as clobetasol propionate may diminish the antineoplastic effect of aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin. |
| Target | Interleukin-2 receptor subunit beta,Interleukin-2 receptor subunit alpha,Cytokine receptor common subunit gamma |
| Brand Name | Proleukin |
| Company | Bayer Healthcare , Chiron Corp. , Novartis AG , Physicians Total Care Inc. , Prometheus Laboratories Inc. |
| Brand Description | Bayer Healthcare , Chiron Corp. , Novartis AG , Physicians Total Care Inc. , Prometheus Laboratories Inc. |
| Prescribed For | Treating skin cancer and kidney cancer that has spread to other parts of the body. |
| Chemical Name | desalanyl-1, serine-125 human interleukin-2 |
| Formulation | Proleukin is supplied in single-use vials intended for intravenous administration. When reconstituted with 1.2 mL Sterile Water for Injection, USP, each mL contains 18 million International Units (1.1 mg) Proleukin, 50 mg mannitol, and 0.18 mg sodium dod |
| Physical Appearance | Sterile, white to off-white, lyophilized cake |
| Route of Administration | Intravenous administration |
| Recommended Dosage | The recommended Proleukin treatment regimen is administered by a 15 minute Intravenous infusion every 8 hours. 600,000 International Units/kg (0.037 mg/kg) dose administered every 8 hours by a 15 minute Intravenous infusion for a maximum of 14 doses. ollowing 9 days of rest, the schedule is repeated for another 14 doses, for a maximum of 28 doses per course, as tolerated. |
| Contraindication | Proleukin is contraindicated in patients with a known history of hypersensitivity to interleukin-2 or any component of the Proleukin formulation. |
| Side Effects | Anxiety; dizziness; general body discomfort; increased cough; infection; loss of appetite; pain; runny nose; weakness. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |