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Information on EC 3.4.17.11 - glutamate carboxypeptidase
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EC Tree
3.4.17.11 glutamate carboxypeptidaseSpecify your search results
Word Map
- 3.4.17.11
- methotrexate
-
prodrugs
-
high-dose
-
antibody-directed
- leucovorin
-
hdmtx
-
methotrexate-induced
-
gene-directed
- naaladase
-
gdept
-
antibody-enzyme
- medicine
-
anti-cea
-
anti-carcinoembryonic
-
prodrug-activating
- gcpii
- 2-pmpa
-
n-acetyl-aspartyl-glutamate
-
dampa
- drug development
- diagnostics
- pharmacology
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
release of C-terminal glutamate residues from a wide range of N-acylating moieties, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl and pteroyl groups
Synonyms
glucarpidase, carboxypeptidase g2, cpdg2, glutamate carboxypeptidase, carboxypeptidase g1, carboxypeptidase g, glutamyl carboxypeptidase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
carboxypeptidase G
-
-
-
-
carboxypeptidase G1
-
-
-
-
carboxypeptidase G2
CPG2
folate hydrolase G2
-
-
-
-
glucarpidase
glutamate carboxypeptidase
glutamyl carboxypeptidase
-
-
-
-
N-pteroyl-L-glutamate hydrolase
-
-
-
-
pteroylmonoglutamic acid hydrolase G2
-
-
-
-
carboxypeptidase G2
-
-
-
-
glutamate carboxypeptidase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of C-terminal glutamate residues from a wide range of N-acylating moieties, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl and pteroyl groups
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
9074-87-7
not distinguishable from EC 3.4.19.9 in Chemical Abstracts
94894-32-3
Pseudomonas isoenzyme 2
94894-33-4
Pseudomonas isoenzyme 2 precursor
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzyl-L-glutamic acid + H2O
(2-chloroethyl)-(2-(methylsulfoyloxyethyl)amino)aminobenzoic acid + L-glutamate
-
a prodrug
-
-
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diylcarbamoylimino])dipentanedioic acid + 2 H2O
(11aS,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one) + ?
-
-
-
-
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diyloxycarbonylimino])dipentanedioic acid + 2 H2O
3-hydroxybenzyl 4-hydroxybenzyl (11S,11aS,11'S,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate) + 2 N-carboxy-L-glutamate
-
-
-
-
?
(4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
a trifluorinated prodrug
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
(4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
a trifluorinated prodrug
-
-
?
(4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-2,3,5-trifluorobenzoic acid + L-glutamate
-
a trifluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
2,4-dihydroxypteroyl-L-glutamic acid + H2O
2,4-dihydroxypteroate + L-Glu
-
-
-
-
?
3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoic acid + H2O
?
-
cognate drug
-
-
?
3,5-difluoro-4-[bis(2-iodoethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
3,5-difluorobenzoyl-L-glutamate + H2O
3,5-difluorobenzoate + L-glutamate
-
chemical exchange saturation transfer magnetic resonance study, i.e. CEST-MR to monitor the release of glutamate. CEST-MR affords the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo
-
?
3,5-difluorobenzoyl-L-glutamic acid + H2O
3,5-difluorobenzoic acid + L-glutamate
-
-
-
-
?
3-fluoro-4-[bis(2-chloroethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
4-amino-N10-methylpteroylaspartic acid + H2O
4-amino-N10-methylpteroate + Asp
-
-
-
-
?
4-aminobenzoyl-L-glutamic acid + H2O
4-aminobenzoate + glutamate
-
-
-
-
?
4-aminobenzoyl-L-glutamic acid + H2O
4-aminobenzoate + L-glutamate
-
-
-
?
4-[(2-chloroethyl)(2-methylsulphonyloxyethyl)amino]benzoic acid + H2O
?
-
cognate drug
-
-
?
4-[(2-chloroethyl)-(2-methylsulphonyloxyethyl)amino]benzoyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
4-[bis(2-iodoethyl)-amino]-phenyloxycarbonyl-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
7-hydroxy-methotrexate + H2O
7-hydroxy-4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
di-tert-butyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenyloxycarbonyl-L-glutamic acid + H2O
?
-
-
-
-
?
diallyl 4-[N-[4'-bis(2''-chloroethyl)aminophenyl]-N-methylcarbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid + H2O
?
-
-
-
-
?
diallyl 4-[[2'-[N,N-bis(2''-chloroethyl)amino]phenyl]carbamoyloxymethyl]phenylcarbamoyl-L-glutamic acid + H2O
?
-
-
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenoxy]carbonyl)-L-glutamic acid + H2O
(11aS)-7,8-dimethoxy-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one + ?
-
-
-
-
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenyl]carbamoyl)-L-glutamic acid + H2O
? + L-glutamate
-
-
-
-
?
N-benzyloxycarbonyl-L-aspartic acid + H2O
benzyl carbonate + L-Asp
-
-
-
-
?
N-benzyloxycarbonyl-L-glutamic acid + H2O
benzyl carbonate + L-Glu
-
no activity with D-glutamic acid
-
-
?
N-benzyloxycarbonyl-L-glutamine + H2O
benzyl carbonate + L-Gln
-
-
-
-
?
[4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
[4-[bis(2-hydroxyethyl)amino]-3,5-difluorobenzoyl]-L-glutamic acid + H2O
?
-
prodrug activated by CPG2
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
inactivation of the antitumor drug
-
-
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
the pharmacolically active 6S-stereoisomer is degraded faster than the inactive 6R-stereoisomer
-
-
?
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
-
-
-
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
-
-
-
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
-
-
?
4-aminopteroylglutamic acid + H2O
4-aminopteroate + Glu
-
i.e. aminopterin
-
-
?
4-aminopteroylglutamic acid + H2O
4-aminopteroate + Glu
-
i.e. aminopterin
-
-
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
i.e. leucovorin
-
-
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
i.e. leucovorin
-
-
?
5-formyltetrahydrofolic acid + H2O
5-formylpteroate + Glu
-
i.e. leucovorin
-
-
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
-
-
-
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
the water soluble substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
-
-
?
folic acid + H2O
pteroic acid + glutamic acid
-
i.e. pteroyl-L-glutamic acid
-
r
folic acid + H2O
pteroic acid + glutamic acid
-
equilibrium lies far towards hydrolysis
-
r
folic acid + H2O
pteroic acid + glutamic acid
-
no activity with pteroyl-D-glutamic acid
-
r
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
highly reduced clearance of the drug in enzyme-defective patients leads to severe neutropenia, mucositis, nephrotoxicity, neurotoxicity, and elevation of liver enzymes in plasma
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
i.e. amethopterin
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
-
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
related toxicity, overview, rapid inactivation of methotrexate by CPDG2, the product DAMPA is eliminated more raoidly than methotrexate
i.e. DAMPA
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
-
-
-
?
additional information
?
-
-
releases the carboxy-terminal glutamyl moiety of derivatives of pteroyl-mono-L-glutamic acid
-
-
?
additional information
?
-
-
substituents on N5 of the pteridine ring decrease the velocity of hydrolysis
-
-
?
additional information
?
-
-
synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy, overview
-
-
?
additional information
?
-
-
specifically cleaves terminal glutamic acid amines
-
-
?
additional information
?
-
-
rapid hydrolysis occurs in linkages of the form RCO-Glu and RCO-Gln, whereas those of the form RCO-D-Glu (D-Glu-D-Glu and Z-D-Glu) are not attacked
-
-
?
additional information
?
-
-
no hydrolysis of glutamate or glutamine lacking a free carboxyl alpha-carboxyl
-
-
?
additional information
?
-
-
effects of carboxypeptidase G2 administration to patients with methotrexate-induce renal failure, overview
-
-
?
additional information
?
-
-
enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
-
-
?
additional information
?
-
-
half-lives of prodrugs and drugs, overview
-
-
?
additional information
?
-
-
specifically cleaves terminal glutamic acid amines
-
-
?
additional information
?
-
-
CPG2 cleaves folic acid to pteroic acid and activates a range of bifunctional alkylating agent and antibiotic prodrugs
-
-
?
additional information
?
-
-
enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
-
-
?
additional information
?
-
-
half-lives of prodrugs and drugs, overview
-
-
?
additional information
?
-
-
hydrolyzes the COOH-terminal glutamate of oligopeptides and N-benzyloxycarbonyl glutamates
-
-
?
additional information
?
-
-
lesser activity against aspartate COOH-terminal peptide linkages
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diylcarbamoylimino])dipentanedioic acid + 2 H2O
(11aS,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one) + ?
-
-
-
-
?
(2S,2'S)-2,2'-(pentane-1,5-diylbis[oxy[(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8,10(5H)-diyl]carbonyloxymethanediylbenzene-4,1-diyloxycarbonylimino])dipentanedioic acid + 2 H2O
3-hydroxybenzyl 4-hydroxybenzyl (11S,11aS,11'S,11a'S)-8,8'-[pentane-1,5-diylbis(oxy)]bis(11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate) + 2 N-carboxy-L-glutamate
-
-
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
(6R,S)-leucovorin + H2O
N-(6R,S)-5-formyl-5,6,7,8-tetrahydropteroic acid + L-glutamate
-
inactivation of the antitumor drug
-
-
?
4-([bis(2-iodoethyl)amino]-phenyl)oxycarbonyl-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-phenylcarbonate + L-glutamate
-
substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
-
-
?
7-hydroxy-methotrexate + H2O
7-hydroxy-4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
-
-
-
?
diethylstilbestrol-glutamate + H2O
diethylstilbestrol + L-glutamate
-
the water soluble substrate can be used as a prodrug that is hydrolyzed to yield the active drug in an antibody directed enzyme prodrug therapy
-
-
?
methotrexate + H2O
4-amino-4-deoxy-N10-methylpteroic acid + L-glutamate
-
highly reduced clearance of the drug in enzyme-defective patients leads to severe neutropenia, mucositis, nephrotoxicity, neurotoxicity, and elevation of liver enzymes in plasma
-
-
?
methotrexate + H2O
4-[(2,4-diamino-6-(pteridinyl)methyl)-methylamino]-benzoic acid + L-glutamate
-
related toxicity, overview, rapid inactivation of methotrexate by CPDG2, the product DAMPA is eliminated more raoidly than methotrexate
i.e. DAMPA
-
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenoxy]carbonyl)-L-glutamic acid + H2O
(11aS)-7,8-dimethoxy-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one + ?
-
-
-
-
?
N-([4-[([[(11S,11aS)-11-hydroxy-7,8-dimethoxy-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]carbonyl]oxy)methyl]phenyl]carbamoyl)-L-glutamic acid + H2O
? + L-glutamate
-
-
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-bromoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
(4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoyl)-L-glutamic acid + H2O
4-[bis(2-iodoethyl)amino]-3,5-difluorobenzoic acid + L-glutamate
-
a difluorinated prodrug
-
-
?
additional information
?
-
-
synthesis and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy, overview
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-
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specifically cleaves terminal glutamic acid amines
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effects of carboxypeptidase G2 administration to patients with methotrexate-induce renal failure, overview
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enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
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specifically cleaves terminal glutamic acid amines
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CPG2 cleaves folic acid to pteroic acid and activates a range of bifunctional alkylating agent and antibiotic prodrugs
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enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs, overview
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
additional information
Zn2+
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each subunit of the dimer constists of a larger catalytic domain containing two zinc ions at the active site and a separate smaller domain that forms the dimer interface
Zn2+
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contains 4 atoms of zinc per enzyme molecule, which are required for full activity
Zn2+
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is the only heavy metal ion capable of restoring full activity when the endogenous metal is removed by incubation with the chelating resin
additional information
Mg2+ inhibits the activity of the recombinant enzyme
additional information
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Mg2+ inhibits the activity of the recombinant enzyme
additional information
Mn2+ inhibits the activity of the recombinant enzyme
additional information
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Mn2+ inhibits the activity of the recombinant enzyme
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-2-[(3-aminonaphthalene-2-carbonyl)amino]pentanedioic acid
CP06
(2R)-2-[[3-(2-methylpropanamido)naphthalene-2-carbonyl]amino]pentanedioic acid
CP67
(4-[bis(2-chloroethyl)amino]-2,3,5,6-tetrafluorobenzoyl)-L-glutamic acid
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prodrug, competitive inhibition
(4-[bis(2-iodoethyl)amino]-2,3,5,6-tetrafluorobenzoyl)-L-glutamic acid
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prodrug, competitive inhibition
4-Aminopteroylaspartic acid
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hydrolysis of 4-amino-N10-methylpteroylglutamic acid
L-aspartic acid
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weak inhibition of hydrolysis of 4-amino-N10-methylpteroylglutamic acid
N-Benzyloxycarbonyl glutamic acid
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hydrolysis of 4-amino-N10-methylpteroylglutamic acid
N-Benzyloxycarbonylaspartic acid
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hydrolysis of 4-amino-N10-methylpteroylglutamic acid
L-Glutamic acid
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hydrolysis of 4-amino-N10-methylpteroylglutamic acid, no inhibition by D-glutamic acid
additional information
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in vitro cytotoxicity of the prodrugs in LS174T colon cell line, overview
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additional information
Mg2+ inhibits the activity of the recombinant enzyme; Mn2+ inhibits the activity of the recombinant enzyme
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additional information
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Mg2+ inhibits the activity of the recombinant enzyme; Mn2+ inhibits the activity of the recombinant enzyme
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additional information
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orally available glutamate carboxypeptidase inhibitor E2072 (commercial preparation) has a neuroprotective effect on three well-established animal models of chemotherapy. It improves the chemotherapy-induced nerve conduction velocity deficits
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acute Kidney Injury
Acute renal failure post high dose methotrexate infusion successfully managed with high dose folinic Acid and high flux dialysis.
Acute Kidney Injury
Carboxypeptidase G2 rescue in a 79 year-old patient with cranial lymphoma after high-dose methotrexate induced acute renal failure.
Acute Kidney Injury
Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.
Acute Kidney Injury
Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients with Acute Kidney Injury After High-Dose Methotrexate Therapy.
Acute Kidney Injury
Fixed-Dose Glucarpidase for Toxic Methotrexate Levels and Acute Kidney Injury in Adult Lymphoma Patients: Case Series.
Acute Kidney Injury
Recovery of methotrexate-induced anuric acute kidney injury after glucarpidase therapy.
Acute Kidney Injury
Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients.
Autoimmune Diseases
Soluble expression, purification and functional characterisation of carboxypeptidase G2 and its individual domains.
Brain Injuries
Neuroprotective effects of a dendrimer-based glutamate carboxypeptidase inhibitor on superoxide dismutase transgenic mice after neonatal hypoxic-ischemic brain injury.
Breast Neoplasms
Combined impact of polymorphism of folate metabolism genes; glutamate carboxypeptidase, methylene tetrahydrofolate reductase and methionine synthase reductase on breast cancer susceptibility in kashmiri women.
Breast Neoplasms
Regressions of established breast carcinoma xenografts by carboxypeptidase G2 suicide gene therapy and the prodrug CMDA are due to a bystander effect.
Carcinoma
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.
Carcinoma
Suicide gene therapy of human colon carcinoma xenografts using an armed oncolytic adenovirus expressing carboxypeptidase G2.
Carcinoma, Hepatocellular
Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2.
Carcinoma, Non-Small-Cell Lung
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
Choriocarcinoma
The potential of carboxypeptidase G2-antibody conjugates as anti-tumour agents. I. Preparation of antihuman chorionic gonadotrophin-carboxypeptidase G2 and cytotoxicity of the conjugate against JAR choriocarcinoma cells in vitro.
Choriocarcinoma
The potential of carboxypeptidase G2: antibody conjugates as anti-tumour agents. II. In vivo localising and clearance properties in a choriocarcinoma model.
Colonic Neoplasms
Carboxypeptidase G2 and trimetrexate cause growth delay of human colonic cancer cells in vitro.
Colorectal Neoplasms
Antibody-directed enzyme prodrug therapy: efficacy and mechanism of action in colorectal carcinoma.
Colorectal Neoplasms
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
Hodgkin Disease
Successful carboxypeptidase G2 rescue of a high-risk elderly Hodgkin lymphoma patient with methotrexate intoxication and renal failure.
Leukemia
Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.
Liver Neoplasms
Plasma glutamate carboxypeptidase is a negative regulator in liver cancer metastasis.
Lung Neoplasms
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
Lung Neoplasms
Hypermethylation of PGCP gene is associated with human bronchial epithelial cells immortalization.
Lymphoma
Carboxypeptidase G2 rescue in a 79 year-old patient with cranial lymphoma after high-dose methotrexate induced acute renal failure.
Lymphoma
Fixed-Dose Glucarpidase for Toxic Methotrexate Levels and Acute Kidney Injury in Adult Lymphoma Patients: Case Series.
Lymphoma
Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.
Medulloblastoma
Comparative effects of citrovorum factor and carboxypeptidase G1 on cerebrospinal fluid-methotrexate pharmacokinetics.
Melanoma
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.
Neoplasm Metastasis
Plasma glutamate carboxypeptidase is a negative regulator in liver cancer metastasis.
Neoplasms
Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds.
Neoplasms
Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey.
Neoplasms
Attenuated Salmonella targets prodrug activating enzyme carboxypeptidase G2 to mouse melanoma and human breast and colon carcinomas for effective suicide gene therapy.
Neoplasms
Biodistribution of an antibody-enzyme conjugate for antibody-directed enzyme prodrug therapy in nude mice bearing a human colon adenocarcinoma xenograft.
Neoplasms
Catalytic activity of an in vivo tumor targeted anti-CEA scFv::carboxypeptidase G2 fusion protein.
Neoplasms
Characterisation of the Carboxypeptidase G2 Catalytic Site and Design of New Inhibitors for Cancer Therapy.
Neoplasms
Characterization of a Stable Form of Carboxypeptidase G2 (Glucarpidase), a Potential Biobetter Variant, From Acinetobacter sp. 263903-1.
Neoplasms
Coupling of a Novel TIMP3 Peptide to Carboxypeptidase G2 for Pro-Drug Activation at the Tumour Site.
Neoplasms
Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy.
Neoplasms
Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance.
Neoplasms
Engineering carboxypeptidase G2 circular permutations for the design of an autoinhibited enzyme.
Neoplasms
Functional overexpression and purification of a codon optimized synthetic glucarpidase (carboxypeptidase G2) in Escherichia coli.
Neoplasms
Glucarpidase (carboxypeptidase g2) intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy.
Neoplasms
Hyperpolarized (13)C magnetic resonance detection of carboxypeptidase G2 activity.
Neoplasms
In vitro studies on CNGRC-CPG2 fusion proteins for ligand-directed enzyme prodrug therapy for targeted cancer therapy.
Neoplasms
Inactivation and clearance of an anti-CEA carboxypeptidase G2 conjugate in blood after localisation in a xenograft model.
Neoplasms
Induction of apoptosis by the ADEPT agent ZD2767: comparison with the classical nitrogen mustard chlorambucil and a monofunctional ZD2767 analogue.
Neoplasms
Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment.
Neoplasms
Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study.
Neoplasms
Modifying an immunogenic epitope on a therapeutic protein: a step towards an improved system for antibody-directed enzyme prodrug therapy (ADEPT).
Neoplasms
Novel prodrugs of alkylating agents derived from 2-fluoro- and 3-fluorobenzoic acids for antibody-directed enzyme prodrug therapy.
Neoplasms
Novel prodrugs which are activated to cytotoxic alkylating agents by carboxypeptidase G2.
Neoplasms
Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT).
Neoplasms
Production of "biobetter" glucarpidase variants to improve drug detoxification and antibody directed enzyme prodrug therapy for cancer treatment.
Neoplasms
Production of "biobetter" variants of glucarpidase with enhanced enzyme activity.
Neoplasms
Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients.
Neoplasms
Soluble expression, purification and functional characterisation of carboxypeptidase G2 and its individual domains.
Neoplasms
Suicide gene therapy of human colon carcinoma xenografts using an armed oncolytic adenovirus expressing carboxypeptidase G2.
Neoplasms
Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2.
Neoplasms
Three new prodrugs for suicide gene therapy using carboxypeptidase G2 elicit bystander efficacy in two xenograft models.
Neoplasms
Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2.
Neural Tube Defects
Role of parental folate pathway single nucleotide polymorphisms in altering the susceptibility to neural tube defects in South India.
Osteosarcoma
2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate-induced nephrotoxicity.
Osteosarcoma
Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients with Acute Kidney Injury After High-Dose Methotrexate Therapy.
Peripheral Nervous System Diseases
Glutamate Carboxypeptidase Inhibition Reduces the Severity of Chemotherapy-Induced Peripheral Neurotoxicity in Rat.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Novel risk factors for glucarpidase use in pediatric acute lymphoblastic leukemia: Hispanic ethnicity, age, and the ABCC4 gene.
Prostatic Neoplasms
68Ga/64Cu PSMA bio-distribution in prostate cancer patients: potential pitfalls for different tracers.
Prostatic Neoplasms
A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules.
Prostatic Neoplasms
Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer.
Prostatic Neoplasms
Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey.
Prostatic Neoplasms
Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients.
Prostatic Neoplasms
Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer.
Renal Insufficiency
Carboxypeptidase G2 rescue in delayed methotrexate elimination in renal failure.
Renal Insufficiency
Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure.
Renal Insufficiency
Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in vitro: implications for the application in case of methotrexate intoxications.
Renal Insufficiency
Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure.