Gemtuzumab ozogamicin

Identification

Name
Gemtuzumab ozogamicin
Accession Number
DB00056  (BTD00077, BIOD00077)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Gemtuzumab ozogamicin is a recombinant humanized IgG4 kappa antibody which is conjugated with calicheamicin derivative, a cytotoxic antitumor antibiotic isolated from fermentation of Micromonospora echinospora ssp. calichensis. Gemtuzumab ozogamicin has approximately 50% of the antibody loaded with 4-6 moles calicheamicin per mole of antibody [FDA Label]. The antibody is specifically directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). By binding to the CD33 antigen on tumors, the cytotoxic agent blocks the growth of cancerous cells and causes cell death.

Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by FDA as a treatment for patients with CD33-positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy [1]. However, it was voluntarily withdrawn from the market in 2010 due to safety concerns, increased patient deaths and insufficient evidence of clinical benefit during confirmatory trials [5]. On September 1 2017, gemtuzumab ozogamicin was again approved for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia but with a lower dosing regimen and a different schedule in combination with chemotherapy or on its own [5]. It is also indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory) [5].

Protein structure
Db00056
Protein chemical formula
Not Available
Protein average weight
151500.0 Da (range)
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
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MylotargInjection, powder, lyophilized, for solution5 mg/5mLIntravenousWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.2017-09-07Not applicableUs
International/Other Brands
Mylotarg (Wyeth)
Categories
UNII
8GZG754X6M
CAS number
220578-59-6

Pharmacology

Indication

Indicated for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. Indicated for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory).

Structured Indications
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 site-specific DNA double strand breaks via formation of a p-benzene diradical [4]. Eventually, cell death is induced.

TargetActionsOrganism
AMyeloid cell surface antigen CD33
antibody
Human
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHuman
UComplement C1r subcomponentNot AvailableHuman
UComplement C1q subcomponent subunit ANot AvailableHuman
UComplement C1q subcomponent subunit BNot AvailableHuman
UComplement C1q subcomponent subunit CNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHuman
UComplement C1s subcomponentNot AvailableHuman
UHigh affinity immunoglobulin gamma Fc receptor INot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-aNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-bNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-cNot AvailableHuman
Absorption

In pediatric patients receiving a dose level of 9mg/m^2, the peak plasma concentration (Cmax) was approximately 3.47±1.04 mg/L with the AUC of 136 ±107 mg * h/L [4].

Volume of distribution

The volume of distribution at steady state (Vss) was approximately 6.5 ± 5.5 L in pediatric patients receiving a dose level of 9mg/m^2 [4].

Protein binding
Not Available
Metabolism

Metabolic studies indicate hydrolytic release of the calicheamicin derivative from gemtuzumab ozogamicin. The drug is most likely removed by opsonization via the reticuloendothelial system.

Route of elimination
Not Available
Half life

In pediatric patients receiving a dose level of 9mg/m^2, the half life was approximately 64±44 h after the first dose [4].

Clearance

The mean clearance rate was approximately 0.12±0.15 L/h/m^2 in pediatric patients receiving a dose level of 9mg/m^2 [4].

Toxicity

The most frequently reported toxicities are myelosuppression and hepatic veno-occlusive disorder.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Belimumab.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Gemtuzumab ozogamicin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Gemtuzumab ozogamicin.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
ClozapineThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Clozapine.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Gemtuzumab ozogamicin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Gemtuzumab ozogamicin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Gemtuzumab ozogamicin.Approved, Investigational
FingolimodGemtuzumab ozogamicin may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Gemtuzumab ozogamicin.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Leflunomide.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Gemtuzumab ozogamicin.Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Natalizumab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Gemtuzumab ozogamicin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Gemtuzumab ozogamicin.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Gemtuzumab ozogamicin.Experimental
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Gemtuzumab ozogamicin.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Gemtuzumab ozogamicin.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Gemtuzumab ozogamicin.Investigational
TofacitinibGemtuzumab ozogamicin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Gemtuzumab ozogamicin.Approved, Investigational
Varicella Zoster Vaccine (Live/Attenuated)The therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Gemtuzumab ozogamicin.Approved
Food Interactions
Not Available

References

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]
  4. Buckwalter M, Dowell JA, Korth-Bradley J, Gorovits B, Mayer PR: Pharmacokinetics of gemtuzumab ozogamicin as a single-agent treatment of pediatric patients with refractory or relapsed acute myeloid leukemia. J Clin Pharmacol. 2004 Aug;44(8):873-80. [PubMed:15286091]
  5. FDA Press Announcements: FDA approves Mylotarg for treatment of acute myeloid leukemia [Link]
External Links
PubChem Substance
46505767
ChEMBL
CHEMBL1201506
Therapeutic Targets Database
DAP000390
PharmGKB
PA164749431
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gemtuzumab_ozogamicin
ATC Codes
L01XC05 — Gemtuzumab
FDA label
Download (160 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Juvenile Myelomonocytic Leukemia / Myelodysplastic Syndrome1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1TerminatedTreatmentJuvenile Myelomonocytic Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1TerminatedTreatmentLeukemias1
1, 2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Chronic Lymphocytic Leukaemia (CLL) / Myelodysplastic Syndrome1
1, 2CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentMyeloid Leukemias1
1, 2Unknown StatusTreatmentAllogeneic Transplantation / Leukemia Acute Myeloid Leukemia (AML)1
2Active Not RecruitingTreatmentAdult Acute Megakaryoblastic Leukemia / Adult Acute Monoblastic Leukemia / Adult Acute Monocytic Leukemia / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With Maturation / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Adult Erythroleukemia / Adult Pure Erythroid Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Secondary Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentNovo Acute Myeloid Leukemia1
2CompletedNot AvailableAcute Myelogenous Leukaemia (AML)1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome2
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)3
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentLeukemias10
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes3
2RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome2
2RecruitingTreatmentLeukemias1
2TerminatedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Untreated Adult Acute Myeloid Leukemia1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Lymphoblastic Leukemia, Acute1
2Unknown StatusTreatmentMyelodysplastic Syndromes1
2WithdrawnTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Promyelocytic Leukemia (M3) / Recurrent Adult Acute Myeloid Leukemia1
2, 3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
2, 3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2, 3TerminatedTreatmentLeukemias1
2, 3Unknown StatusTreatmentLeukemias1
3Active Not RecruitingTreatmentLeukemias2
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
3CompletedTreatmentLeukemia, Myelocytic, Acute1
3CompletedTreatmentLeukemias2
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
4CompletedNot AvailableLeukemia Acute Myeloid Leukemia (AML)1
4CompletedTreatmentAcute Myeloblastic Leukemia1
4CompletedTreatmentIntravenous Infusions / Leukemia, Myelocytic, Acute1
Not AvailableAvailableNot AvailableCD33 Positive Acute Myelogenous Leukemia1
Not AvailableNot Yet RecruitingNot AvailableLeukemia Acute Myeloid Leukemia (AML)1
Not AvailableSuspendedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Promyelocytic Leukemia (M3) / Childhood Acute Promyelocytic Leukemia (M3) / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Myeloid Leukemia1

Pharmacoeconomics

Manufacturers
  • Wyeth pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous5 mg/5mL
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)
US5773001No1995-06-302015-06-30Us
US5585089No1993-12-172013-12-17Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not 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 si...
Gene Name
CD33
Uniprot ID
P20138
Uniprot Name
Myeloid cell surface antigen CD33
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...
Gene Name
FCGR3B
Uniprot ID
O75015
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-B
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
Uniprot Name
Complement C1r subcomponent
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) proe...
Gene Name
C1QA
Uniprot ID
P02745
Uniprot Name
Complement C1q subcomponent subunit A
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) proe...
Gene Name
C1QB
Uniprot ID
P02746
Uniprot Name
Complement C1q subcomponent subunit B
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) proe...
Gene Name
C1QC
Uniprot ID
P02747
Uniprot Name
Complement C1q subcomponent subunit C
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...
Gene Name
FCGR3A
Uniprot ID
P08637
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-A
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, activat...
Gene Name
C1S
Uniprot ID
P09871
Uniprot Name
Complement C1s subcomponent
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
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
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 ...
Gene Name
FCGR2A
Uniprot ID
P12318
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-a
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 complex...
Gene Name
FCGR2B
Uniprot ID
P31994
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-b
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 modulat...
Gene Name
FCGR2C
Uniprot ID
P31995
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-c
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]

Drug created on June 13, 2005 07:24 / Updated on November 06, 2017 06:43