BRENDA - Enzyme Database show
show all sequences of 1.1.1.239

The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3

Guise, C.P.; Abbattista, M.R.; Singleton, R.S.; Holford, S.D.; Connolly, J.; Dachs, G.U.; Fox, S.B.; Pollock, R.; Harvey, J.; Guilford, P.; Donate, F.; Wilson, W.R.; Patterson, A.V.; Cancer Res. 70, 1573-1584 (2010)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
enzyme is involved in activation of prodrug PR-104A designed to exploit tumor hypoxia. AKR1C3 protein is detected by Western blot in 7 of 23 cell lines and correlates with oxic PR-104A metabolism. AKR1C3 is unable to sensitize cells to 10 other bioreductive prodrugs and is associated with single-agent PR-104 activity across a panel of 9 human tumor xenograft models. Overexpression in two AKR1C3-negative tumor xenograft models strongly enhances PR-104 antitumor activity. Marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma
Homo sapiens
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
-
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
carcinoma cell
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2-[(2-bromoethyl)(2-[[(2-hydroxyethyl)amino]methyl]-4,6-dinitrophenyl)amino]ethyl methanesulfonate + 2 NADH + 2 H+
i.e. PR-104A, phosphate ester prodrug designed to exploit tumor hypoxia
711670
Homo sapiens
2-[(2-bromoethyl)[4-(hydroxyamino)-2-[[(2-hydroxyethyl)amino]methyl]-6-nitrophenyl]amino]ethyl methanesulfonate + 2 NAD+ + H2O
i.e. PR-104H, enzyme acts as nitroreductase for activation of PR-104A
-
-
-
Application (protein specific)
Application
Commentary
Organism
medicine
enzyme is involved in activation of prodrug PR-104A designed to exploit tumor hypoxia. AKR1C3 protein is detected by Western blot in 7 of 23 cell lines and correlates with oxic PR-104A metabolism. AKR1C3 is unable to sensitize cells to 10 other bioreductive prodrugs and is associated with single-agent PR-104 activity across a panel of 9 human tumor xenograft models. Overexpression in two AKR1C3-negative tumor xenograft models strongly enhances PR-104 antitumor activity. Marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma
Homo sapiens
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
carcinoma cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2-[(2-bromoethyl)(2-[[(2-hydroxyethyl)amino]methyl]-4,6-dinitrophenyl)amino]ethyl methanesulfonate + 2 NADH + 2 H+
i.e. PR-104A, phosphate ester prodrug designed to exploit tumor hypoxia
711670
Homo sapiens
2-[(2-bromoethyl)[4-(hydroxyamino)-2-[[(2-hydroxyethyl)amino]methyl]-6-nitrophenyl]amino]ethyl methanesulfonate + 2 NAD+ + H2O
i.e. PR-104H, enzyme acts as nitroreductase for activation of PR-104A
-
-
-
Expression
Organism
Commentary
Expression
Homo sapiens
marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma
up
Expression (protein specific)
Organism
Commentary
Expression
Homo sapiens
marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma
up
Other publictions for EC 1.1.1.239
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [C]
Temperature Range [C]
Temperature Stability [C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [C] (protein specific)
Temperature Range [C] (protein specific)
Temperature Stability [C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
724719
Matsunaga
Pathophysiological roles of al ...
Homo sapiens
Chem. Biol. Interact.
202
234-242
2013
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Heinrich
Synthesis and structure-activi ...
Homo sapiens
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724916
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2,3-diarylpropenoic acids as s ...
Homo sapiens
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2013
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723866
Jackson
Structure of AKR1C3 with 3-phe ...
Homo sapiens
Acta Crystallogr. Sect. F
68
409-413
2012
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724533
Chen
Crystal structures of AKR1C3 c ...
Homo sapiens
Bioorg. Med. Chem. Lett.
22
3492-3497
2012
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724538
Sinreih
N-Benzoyl anthranilic acid der ...
Homo sapiens
Bioorg. Med. Chem. Lett.
22
5948-5951
2012
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725153
Miller
Aldo-keto reductase family 1 m ...
Homo sapiens
Int. J. Clin. Exp. Pathol.
5
278-289
2012
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Selective inhibitors of aldo-k ...
Homo sapiens
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55
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2012
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725825
Byrns
Overexpression of aldo-keto re ...
Homo sapiens
J. Steroid Biochem. Mol. Biol.
130
7-15
2012
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724517
Adeniji
Discovery of substituted 3-(ph ...
Homo sapiens
Bioorg. Med. Chem. Lett.
21
1464-1468
2011
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711670
Guise
The bioreductive prodrug PR-10 ...
Homo sapiens
Cancer Res.
70
1573-1584
2010
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712882
Byrns
Aldo-keto reductase 1C3 expres ...
Homo sapiens
J. Steroid Biochem. Mol. Biol.
118
177-187
2010
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713574
Ashley
Developmental evaluation of al ...
Homo sapiens
Urology
76
67-72
2010
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725152
Zakharov
Suppressed expression of type ...
Homo sapiens
Int. J. Clin. Exp. Pathol.
3
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2010
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712571
Nakamura
Type 5 17-hydroxysteroid dehy ...
Homo sapiens
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94
2192-2198
2009
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688137
Azzarello
Tissue distribution of human A ...
Homo sapiens, Rattus norvegicus
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56
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2008
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670259
Ngatcha
3beta-Alkyl-androsterones as i ...
Homo sapiens
Mol. Cell. Endocrinol.
248
225-232
2006
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673341
Fung
Increased expression of type 2 ...
Homo sapiens
Endocr. Relat. Cancer
13
169-180
2006
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287209
Krazeisen
Phytoestrogens inhibit human 1 ...
Homo sapiens
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171
151-162
2001
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287210
Stupans
Testosterone dehydrogenase act ...
Homo sapiens, Macropus eugenii, Phascolarctos cinereus, Rattus norvegicus
Comp. Biochem. Physiol. B
125
245-250
2000
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Carre
Characterization and solubizat ...
Homo sapiens
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46
265-267
1993
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287212
Dumont
Expression of human 17beta-hyd ...
Homo sapiens
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41
605-608
1992
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286355
Sawada
Kinetic and stereochemical cha ...
Mesocricetus auratus
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109
770-775
1991
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286354
Ohmura
Demonstration of 3alpha(17beta ...
Mesocricetus auratus
Biochem. J.
266
583-589
1990
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13
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287213
Itagaki
Purification and characterizat ...
Ilyonectria destructans
J. Biochem.
103
1039-1044
1988
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6
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287214
Payne
Isolation of novel microbiol 3 ...
Alcaligenes sp.
J. Biol. Chem.
260
13648-13655
1985
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287215
Blomquist
Microsomal 17beta-hydroxystero ...
Cavia porcellus
J. Steroid Biochem.
8
193-198
1977
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287216
Markert
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Enzyminduktion bei Streptomyce ...
Streptomyces exfoliatus
Hoppe-Seyler's Z. Physiol. Chem.
356
1843-1852
1975
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3
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287217
Ghraf
11beta- und 17beta-Hydroxyster ...
Rattus norvegicus
Hoppe-Seyler's Z. Physiol. Chem.
354
299-305
1973
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287218
Endahl
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Separation of a triphosphopyri ...
Cavia porcellus
J. Biol. Chem.
235
2793-2796
1960
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1
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287219
Villee
Some properties of the pyridin ...
Cavia porcellus
J. Biol. Chem.
235
3615-3619
1960
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287220
Sweat
Preparation and characterizati ...
Bos taurus
J. Biol. Chem.
185
75-84
1950
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