| Primary information |
|---|
| ThPP ID | Th1159 |
| Therapeutic Peptide/Protein Name | Gemtuzumab ozogamicin |
| Sequence | Light Chain 1: QIVLTQSPAIMSASPGEKVTITCSASSSISYMHWF view full sequnce in fasta |
| Functional Classification | IIb |
| Molecular Weight | 151000 to 153000 |
| Chemical Formula | N.A. |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | 61 (FAB fr |
| Half Life | N.A. |
| Description | Recombinant humanized IgG4, kappa antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin, isolated from fermentation of a bacterium, Micromonospora echinospora ssp. calichensis. The antibody portion of Mylotarg binds specifically to the CD33 antigen, The anti-CD33 hP67.6 antibody is produced by mammalian cell suspension culture using a myeloma NS0 cell line. |
| Indication/Disease | For treatment of CD33-positive acute myeloid leukemia in patients 60 and over who are not candidates for other chemotherapy. |
| Pharmacodynamics | Used for the treatment of acute myeloid leukemia (AML), mylotarg binds to the CD33 antigen, which is expressed on the surface of leukemic cells in more than 80% of patients with AML. The CD33 antigen is not expressed on pluripotent hematopoietic stem cells or nonhematopoietic cells. This gives mylotarg the selectivity needed to target leukemic cells. |
| Mechanism of Action | Mylotarg is directed against the CD33 antigen expressed by hematopoietic cells. Binding of the anti-CD33 antibody portion of Mylotarg with the CD33 antigen results in the formation of a complex that is internalized. Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell. The released calicheamicin derivative binds to DNA in the minor groove resulting in DNA double strand breaks and cell death. |
| Toxicity | The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder. |
| Metabolism | Most likely removed by opsonization via the reticuloendothelial system |
| Absorption | N.A. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Antineoplastic agents and Immunotoxins |
| Patents Number | US5585089 |
| Date of Issue | 17/12/93 |
| Date of Expiry | 17/12/13 |
| Drug Interaction | Belizumab, Clozapine, Denosumab, Leflunomide, Natalizumab due to adverse effects of these drugs with Gemtuzumab; Pimecrolimus, Roflumilast, Sipuleucel-T, Tacrolimus, Tofacitinib, Trastuzumab due to adverse effects of above immmunosupressants |
| Target | Myeloid cell surface antigen CD33, Low affinity immunoglobulin gamma Fc region receptor III-B, Complement C1r subcomponent, Complement C1q subcomponent subunit A, Complement C1q subcomponent subunit B, Complement C1q subcomponent subunit C, Low affinity immunoglobulin gamma Fc region receptor III-A, Complement C1s subcomponent, High affinity immunoglobulin gamma Fc receptor I, Low affinity immunoglobulin gamma Fc region receptor II-a, Low affinity immunoglobulin gamma Fc region receptor II-b, Low affinity immunoglobulin gamma Fc region receptor II-c |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Mylotarg |
| Company | Wyeth pharmaceuticals inc |
| Brand Discription | Mylotarg (gemtuzumab ozogamicin for Injection) is a chemotherapy agent composed of a recombinant humanized IgG4, kappa antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin, isolated from fermentation of a bacterium, Micromonospora echinospora subsp. calichensis. |
| Prescribed for | Mylotarg (gemtuzumab ozogamicin for injection) is indicated for the treatment of patients with CD33 positive acute myeloid leukemia |
| Chemical Name | N.A. |
| Formulation | 5 mg of drug conjugate (protein equivalent) in an amber vial. The inactive ingredients are: dextran 40; sucrose; sodium chloride; monobasic and dibasic sodium phosphate. |
| Physcial Appearnce | Mylotarg (gemtuzumab ozogamicin for injection) is a sterile, white, preservative-free lyophilized powder |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The recommended dose of Mylotarg (gemtuzumab ozogamicin for injection) is 9 mg/m² , infused over a 2-hour period. |
| Contraindication | Mylotarg (gemtuzumab ozogamicin for injection) is contraindicated in patients with a known hypersensitivity to gemtuzumab ozogamicin or any of its components: anti-CD33 antibody (hP67.6), calicheamicin derivatives, or inactive ingredients. Mylotarg is contraindicated in lactating mothers. |
| Side Effects | Fever, Nausea, Chills, Vomiting, Headache,Dyspnea, Hypotension, Hypertension, Hypoxia |
| Useful Link | http://www.rxlist.com/mylotarg-drug.htm |
| PubMed ID | 12738663, 11466696, 11410481 |
| 3-D Structure | Th1159 (View) or (Download) |