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Identification
NameGemtuzumab ozogamicin
Accession NumberDB00056  (BTD00077, BIOD00077)
TypeBiotech
GroupsApproved, Investigational, Withdrawn
DescriptionRecombinant 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. Gemtuzumab ozogamicin (trade name Mylotarg) was withdrawn in 2010 when a clinical trial showed the drug increased patient death and exhibited no advantages over traditional cancer therapies.
Protein structureDb00056
Related Articles
Protein chemical formulaNot Available
Protein average weightNot Available
Sequences
> Light Chain No. 1
QIVLTQSPAIMSASPGEKVTITCSASSSISYMHWFQQKPGTSPKLWIYTTSNLASGVPAR
FSGSGSGTSYSLTISRMEAEDAATYYCHQRSTYPLTFGSGTKLELK
> Light Chain No. 2
DIQMTQSPSTLSASVGDRVTITCRASQSINTWLAWYQQKPGKAPKLLMYKASSLESGVPS
RFIGSGSGTEFTLTISSLQPDDFATYYCQQYNSDSKMFGQGTKVEVK
> Heavy Chain No. 1
QVQLQQSGAELAKPGASVKMSCKASGYTFTSYRMHWVKQRPGQGLEWIGYINPSTGYTEY
NQKFKDKATLTADKSSSTAYMQLSSLTFEDSAVYYCARGGGVFDYWGQGTTLTVSS
> Heavy Chain No. 2
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRSAIIWVRQAPGQGLEWMGGIVPMFGPPNY
AQKFQGRVTITADESTNTAYMELSSLRSEDTAFYFCAGGYGIYSPEEYNGGLVTVSS
Download FASTA Format
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
MylotargWyeth
Brand mixturesNot Available
SaltsNot Available
Categories
UNII8GZG754X6M
CAS number220578-59-6
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor treatment of CD33-positive acute myeloid leukemia in patients 60 and over who are not candidates for other chemotherapy.
PharmacodynamicsUsed 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 actionMylotarg 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityThe most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
Manufacturers
  • Wyeth pharmaceuticals inc
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Mylotarg 5 mg vial3104.82USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5585089 No1993-12-172013-12-17Us
US5773001 No1995-06-302015-06-30Us
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
References
Synthesis ReferenceNot Available
General References
  1. Bross PF, Beitz J, Chen G, Chen XH, Duffy E, Kieffer L, Roy S, Sridhara R, Rahman A, Williams G, Pazdur R: Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001 Jun;7(6):1490-6. [PubMed:11410481 ]
  2. Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA, David CL, Phan AT, Colburn DE, Rashid A, Estey EH: Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer. 2001 Jul 15;92(2):406-13. [PubMed:11466696 ]
  3. Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, DeAngelo DJ: Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003 Sep 1;102(5):1578-82. Epub 2003 May 8. [PubMed:12738663 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelDownload (54 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.
BevacizumabBevacizumab may increase the cardiotoxic activities of Gemtuzumab ozogamicin.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Gemtuzumab ozogamicin.
ClozapineThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Clozapine.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Gemtuzumab ozogamicin.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Gemtuzumab ozogamicin.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.
DigoxinDigoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Gemtuzumab ozogamicin.
FingolimodGemtuzumab ozogamicin may increase the immunosuppressive activities of Fingolimod.
LeflunomideThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Gemtuzumab ozogamicin.
NatalizumabThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Natalizumab.
OuabainOuabain may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Gemtuzumab ozogamicin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Gemtuzumab ozogamicin.
Rabies vaccineThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Rabies vaccine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Gemtuzumab ozogamicin.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Gemtuzumab ozogamicin.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Gemtuzumab ozogamicin.
TofacitinibGemtuzumab ozogamicin may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Gemtuzumab ozogamicin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antibody
General Function:
Receptor activity
Specific Function:
Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cy...
Gene Name:
CD33
Uniprot ID:
P20138
Molecular Weight:
39824.885 Da
References
  1. Naito K, Takeshita A, Shigeno K, Nakamura S, Fujisawa S, Shinjo K, Yoshida H, Ohnishi K, Mori M, Terakawa S, Ohno R: Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia. 2000 Aug;14(8):1436-43. [PubMed:10942240 ]
  2. Niculescu-Duvaz I: Technology evaluation: gemtuzumab ozogamicin, Celltech Group. Curr Opin Mol Ther. 2000 Dec;2(6):691-6. [PubMed:11249747 ]
  3. van Der Velden VH, te Marvelde JG, Hoogeveen PG, Bernstein ID, Houtsmuller AB, Berger MS, van Dongen JJ: Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood. 2001 May 15;97(10):3197-204. [PubMed:11342449 ]
  4. Bross PF, Beitz J, Chen G, Chen XH, Duffy E, Kieffer L, Roy S, Sridhara R, Rahman A, Williams G, Pazdur R: Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001 Jun;7(6):1490-6. [PubMed:11410481 ]
  5. Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR: Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [PubMed:11432892 ]
  6. McHayleh W, Foon K, Redner R, Sehgal R, Raptis A, Agha M, Luong TM, Schlesselman JJ, Boyiadzis M: Gemtuzumab ozogamicin as first-line treatment in patients aged 70 years or older with acute myeloid leukemia. Cancer. 2010 Jun 15;116(12):3001-5. doi: 10.1002/cncr.25078. [PubMed:20564405 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils.
Gene Name:
FCGR3B
Uniprot ID:
O75015
Molecular Weight:
26215.64 Da
References
  1. Caron PC, Lai LT, Scheinberg DA: Interleukin-2 enhancement of cytotoxicity by humanized monoclonal antibody M195 (anti-CD33) in myelogenous leukemia. Clin Cancer Res. 1995 Jan;1(1):63-70. [PubMed:9815888 ]
  2. Rogler G, Hausmann M, Vogl D, Aschenbrenner E, Andus T, Falk W, Andreesen R, Scholmerich J, Gross V: Isolation and phenotypic characterization of colonic macrophages. Clin Exp Immunol. 1998 May;112(2):205-15. [PubMed:9649182 ]
  3. Ericson SG, Benoit NE, Mills LE, Fanger MW: The effect of recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor on Fc gamma receptor expression and antibody-dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro myeloid maturation. Exp Hematol. 1994 Mar;22(3):283-9. [PubMed:7509291 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type peptidase activity
Specific Function:
C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
Gene Name:
C1R
Uniprot ID:
P00736
Molecular Weight:
80118.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QA
Uniprot ID:
P02745
Molecular Weight:
26016.47 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QB
Uniprot ID:
P02746
Molecular Weight:
26721.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QC
Uniprot ID:
P02747
Molecular Weight:
25773.56 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.
Gene Name:
FCGR3A
Uniprot ID:
P08637
Molecular Weight:
29088.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Ericson SG, Benoit NE, Mills LE, Fanger MW: The effect of recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor on Fc gamma receptor expression and antibody-dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro myeloid maturation. Exp Hematol. 1994 Mar;22(3):283-9. [PubMed:7509291 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase activity
Specific Function:
C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.
Gene Name:
C1S
Uniprot ID:
P09871
Molecular Weight:
76683.905 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Receptor signaling protein activity
Specific Function:
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name:
FCGR1A
Uniprot ID:
P12314
Molecular Weight:
42631.525 Da
References
  1. Ericson SG, Benoit NE, Mills LE, Fanger MW: The effect of recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor on Fc gamma receptor expression and antibody-dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro myeloid maturation. Exp Hematol. 1994 Mar;22(3):283-9. [PubMed:7509291 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens.
Gene Name:
FCGR2A
Uniprot ID:
P12318
Molecular Weight:
35000.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells ...
Gene Name:
FCGR2B
Uniprot ID:
P31994
Molecular Weight:
34043.355 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transmembrane signaling receptor activity
Specific Function:
Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells.
Gene Name:
FCGR2C
Uniprot ID:
P31995
Molecular Weight:
35577.96 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23