Gemtuzumab ozogamicin

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NCI: A recombinant, humanized anti-CD33 monoclonal antibody attached to the cytotoxic antitumor antibiotic calicheamicin. In this conjugate, the antibody binds to and is internalized by tumor cells expressing CD33 antigen (a sialic acid-dependent glycoprotein commonly found on the surface of leukemic blasts), thereby delivering the attached calicheamicin to CD33-expressing tumor cells. Calicheamicin binds to the minor groove of DNA, causing double strand DNA breaks and resulting in inhibition of DNA synthesis.

Inn NameGemtuzumab ozogamicin
Lab CodesCDP-771, CMA-676, WAY-CMA-676, hP67.6-calicheamicin
Trade NamesMylotarg
Chemical NameImmunoglobulin G4-kappa, anti-[Homo sapiens CD33 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67)], humanized monoclonal antibody conjugated to N-acetyl-gamma calicheamicin; gamma4 heavy chain (1-443) [humanized VH (Homo sapiens IGHV1-3*01 (72.90%) -(IGHD) -IGHJ5*01) [8.8.9] (1-116)), IGHG4*01 (CH1 (117-214), hinge S10>P (224) (215-226), CH2 (227-336), CH3 (337-441), CHS (442-443)) (117-443)], (130-218')-disulfide with kappa light chain (1’-218’) [humanized V-KAPPA (Homo sapiens IGKV1- 5*01 (81.90%) -IGKJ1*01) [10.3.9](1'-111') -Homo sapiens IGKC*01, Km3 (112'-218')]; dimer (232-232":235-235")-bisdisulfide; conjugated, on an average of 2 or 3 lysyl (0-6), to N-acetyl-S'-des(methylsulfanyl)-S'-(4-hydrazinyl- 2-methyl-4-oxobutan-2-yl)calicheamicin γ1 via a bifunctional 4-(4-acetylphenoxy)butanoyle (AcBut) linker
Alternate NameImmunoglobulin G4 (anti-(human CD33 (antigen)) (human-mouse monoclonal hP67.6 gamma4-chain)), disulfide with human-mouse monoclonal hP67 6kappa-chain, dimer, methyl ((1R,4Z,8S,13E)-8-((2-O-(4-(acetylethylamino)-2,4-dideoxy-3-O-methyl-alpha-L-threo-pentopyranosyl)-4,6-dideoxy-4-(((2,6-dideoxy-4-S-(4-((6-deoxy-3-O-methyl-alpha-L-mannopyranosyl)oxy)-3-iodo-5,6-dimethoxy-2-methylbenzoyl)-4-thio-beta-D-ribo-hexopyranosyl)oxy)amino)-beta-D-glucopyranosyl)oxy)-13-(2-((3-((1-(4-(4-amino-4-oxobutoxy)phenyl)ethylidene)hydrazino)-1,1-dimethyl-3-oxopropyl)dithio)ethylidene)-1-hydroxy-11-oxobicyclo(7.3.1)trideca-4,9-diene-2,6-diyn-10-yl)carbamate conjugate

Immunoglobulin G4 (human-mouse monoclonal hP67.6 gamma4-chain anti-human antigen CD33), disulfide with human-mouse monoclonal hP67.6 kappa-chain, dimer, conjugate with methyl (1R, 4Z, 8S, 13E)-13-(2-((2-(((p-(3-carbamoylpropoxy)-alpha-methylbenzylidene)hydrazino)carbonyl)-1,1-dimethylethyl)dithio)ethylidene)-8-((4,6-dideoxy-4-(((2,6-dideoxy-4-S-(4-((6-deoxy-3-O-methyl-alpha-L-mannopyranosyl)oxy)-3-iodo-5,6-dimethoxy-o-toluoyl)-4-thio-beta-D-ribo-hexopyranosyl)oxy)amino)-2-O-(2,4-dideoxy-4-(N-ethylacetamido)-3-O-methyl-alpha-L-threo-pentopyranosyl)-beta-D-glucopyranosyl)oxy)-1-hydroxy-11-oxobicyclo(7.3.1)trideca-4,9-diene-2,6-diyne-10-carbamate. Molecular weight is approximately 153,000 daltons
SequenceHeavy chain
EVQLVQSGAE VKKPGSSVKV SCKASGYTIT DSNIHWVRQA PGQSLEWIGY 50
IYPYNGGTDY NQKFKNRATL TVDNPTNTAY MELSSLRSED TAFYYCVNGN 100
PWLAYWGQGT LVTVSSASTK GPSVFPLAPC SRSTSESTAA LGCLVKDYFP 150
EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTKTYTCN 200
VDHKPSNTKV DKRVESKYGP PCPPCPAPEF LGGPSVFLFP PKPKDTLMIS 250
RTPEVTCVVV DVSQEDPEVQ FNWYVDGVEV HNAKTKPREE QFNSTYRVVS 300
VLTVLHQDWL NGKEYKCKVS NKGLPSSIEK TISKAKGQPR EPQVYTLPPS 350
QEEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF 400
FLYSRLTVDK SRWQEGNVFS CSVMHEALHN HYTQKSLSLS LGK 443

Light chain
DIQLTQSPST LSASVGDRVT ITCRASESLD NYGIRFLTWF QQKPGKAPKL 50
LMYAASNQGS GVPSRFSGSG SGTEFTLTIS SLQPDDFATY YCQQTKEVPW 100
SFGQGTKVEV KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV 150
QWKVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV 200
THQGLSSPVT KSFNRGEC 218

Disulfide bridges location
Intra-H (C23-C104) 22-96 143-199 257-317 363-421
22''-96'' 143''-199'' 257''-317'' 363''-421''
Intra-L (C23-C104) 23'-92' 138'-198'
23'''-92''' 138'''-198'''
Inter-H-L (CH1 10-CL 126) 130-218' 130''-218'''
Inter-H-H (h 8, h 11) 222-222'' 225-225''

N-glycosylation sites
H CH2 N84.4:
293, 293''
Fucosylated complex bi-antennary NS0-type glycans
Other post-translational modifications
H CHS K2 C-terminal lysine clipping:
443, 443''

Potential modified residues

Chemical StructureGemtuzumab ozogamicin.png
Cas Registry Number220578-59-6
Orphan Drug StatusYes
Orphan IndicationAcute myeloid leukaemia
New Molecular EntityYes
OriginatorUCB
DeveloperPfizer, Eisai, National Cancer Institute (NCI), Celgene, Chugai, Merck Sharp & Dohme Corp, M.D. Anderson Cancer Center

Mechanism Of ActionCD33 antigen inhibitor
Who Atc CodesL01X-C05 (Gemtuzumab)
Ephmra CodesL1G (Monoclonal Antibody Antineoplastics)

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