BRENDA - Enzyme Database show

Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): Role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs

Byrns, M.; Penning, T.; Chem. Biol. Interact. 178, 221-227 (2009)

Data extracted from this reference:

Application
EC Number
Application
Commentary
Organism
1.1.1.188
medicine
AKR1C3 likely plays important roles in the development of hormone-dependent, and possibly hormone-independent, breast cancer. It is highly expressed in normal breast and upregulated in breast cancer, where its expression is associated with a worse prognosis
Homo sapiens
Cloned(Commentary)
EC Number
Commentary
Organism
1.1.1.188
overexpression of AKR1C3 using a pLNCX retroviral vector in MCF-7 cell line
Homo sapiens
Crystallization (Commentary)
EC Number
Crystallization
Organism
1.1.1.188
AKR1C3 in complex with NADP+ and indomethacin
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
1.1.1.188
4-benzoyl-benzoic acid
;
Homo sapiens
1.1.1.188
4-carboxy-2',4'-dinitrodiphenylamine
;
Homo sapiens
1.1.1.188
4-carboxy-2-aminodiphenylamine
;
Homo sapiens
1.1.1.188
4-chloro-N-(4-tolyl)-anthranilic acid
;
Homo sapiens
1.1.1.188
4-chloro-N-phenylanthranilic acid
;
Homo sapiens
1.1.1.188
4-nitro-N-phenylanthranilic acid
;
Homo sapiens
1.1.1.188
5-methyl-N-phenylanthranilic acid
;
Homo sapiens
1.1.1.188
aspirin
;
Homo sapiens
1.1.1.188
flurbiprofen
;
Homo sapiens
1.1.1.188
Ibuprofen
;
Homo sapiens
1.1.1.188
indomethacin
; inhibits AKR1C3, but does not inhibit highly related AKR1C1 or AKR1C2
Homo sapiens
1.1.1.188
Meclofenamic acid
;
Homo sapiens
1.1.1.188
Mefenamic acid
;
Homo sapiens
1.1.1.188
additional information
AKR1C3 is potently inhibited by non-steroidal anti-inflammatory drugs, which are protective against breast cancer
Homo sapiens
1.1.1.188
N-(4-chlorobenzoyl)-melatonin
exhibits uncompetitive inhibition patterns for the reduction of 9,10-phenanthrenequinone but competitive inhibition patterns for the reduction of androstenedione by AKR1C3
Homo sapiens
1.1.1.188
naproxen
;
Homo sapiens
1.1.1.188
salicylic acid
;
Homo sapiens
1.1.1.188
sulindac
;
Homo sapiens
1.1.1.188
Zomepirac
;
Homo sapiens
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.1.1.188
Homo sapiens
-
-
-
1.1.1.188
Homo sapiens
P42330
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.1.188
breast
normal breast expresses very high levels of AKR1C3 relative to other tissues
Homo sapiens
-
1.1.1.188
breast cancer cell
18fold increase in the median AKR1C3 mRNA levels in breast cancer patients as compared to those without disease
Homo sapiens
-
1.1.1.188
MCF-7 cell
;
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.188
9,10-phenanthrenequinone + NADPH + H+
-
697271
Homo sapiens
?
-
-
-
?
1.1.1.188
prostaglandin D2 + NADPH + H+
-
697271
Homo sapiens
9alpha,11beta-prostaglandin F2 + NADP+
-
-
-
?
1.1.1.188
prostaglandin H2 + NADPH + H+
-
697271
Homo sapiens
prostaglandin F2alpha + NADP+
-
-
-
?
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
1.1.1.188
NADPH
;
Homo sapiens
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.1.1.188
0.0003
-
Mefenamic acid
;
Homo sapiens
1.1.1.188
0.00038
-
4-carboxy-2',4'-dinitrodiphenylamine
;
Homo sapiens
1.1.1.188
0.0014
-
4-chloro-N-(4-tolyl)-anthranilic acid
;
Homo sapiens
1.1.1.188
0.0019
-
4-benzoyl-benzoic acid
;
Homo sapiens
1.1.1.188
0.0019
-
4-nitro-N-phenylanthranilic acid
;
Homo sapiens
1.1.1.188
0.0029
-
4-chloro-N-phenylanthranilic acid
;
Homo sapiens
1.1.1.188
0.0034
-
N-(4-chlorobenzoyl)-melatonin
-
Homo sapiens
1.1.1.188
0.0073
-
5-methyl-N-phenylanthranilic acid
;
Homo sapiens
1.1.1.188
0.01
-
4-carboxy-2-aminodiphenylamine
;
Homo sapiens
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
1.1.1.188
0.00039
-
;
Homo sapiens
Mefenamic acid
1.1.1.188
0.0004
-
;
Homo sapiens
4-carboxy-2',4'-dinitrodiphenylamine
1.1.1.188
0.0007
-
;
Homo sapiens
Meclofenamic acid
1.1.1.188
0.0014
-
;
Homo sapiens
naproxen
1.1.1.188
0.0015
-
;
Homo sapiens
4-chloro-N-(4-tolyl)-anthranilic acid
1.1.1.188
0.002
-
;
Homo sapiens
4-benzoyl-benzoic acid
1.1.1.188
0.002
-
;
Homo sapiens
4-nitro-N-phenylanthranilic acid
1.1.1.188
0.0023
-
;
Homo sapiens
indomethacin
1.1.1.188
0.003
-
;
Homo sapiens
4-chloro-N-phenylanthranilic acid
1.1.1.188
0.0034
-
;
Homo sapiens
sulindac
1.1.1.188
0.0078
-
;
Homo sapiens
flurbiprofen
1.1.1.188
0.0099
-
;
Homo sapiens
Ibuprofen
1.1.1.188
0.011
-
;
Homo sapiens
4-carboxy-2-aminodiphenylamine
1.1.1.188
0.011
-
;
Homo sapiens
5-methyl-N-phenylanthranilic acid
1.1.1.188
0.04
-
;
Homo sapiens
Zomepirac
1.1.1.188
0.77
-
;
Homo sapiens
salicylic acid
1.1.1.188
1.2
-
;
Homo sapiens
aspirin
Application (protein specific)
EC Number
Application
Commentary
Organism
1.1.1.188
medicine
AKR1C3 likely plays important roles in the development of hormone-dependent, and possibly hormone-independent, breast cancer. It is highly expressed in normal breast and upregulated in breast cancer, where its expression is associated with a worse prognosis
Homo sapiens
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
1.1.1.188
overexpression of AKR1C3 using a pLNCX retroviral vector in MCF-7 cell line
Homo sapiens
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
1.1.1.188
NADPH
-
Homo sapiens
Crystallization (Commentary) (protein specific)
EC Number
Crystallization
Organism
1.1.1.188
AKR1C3 in complex with NADP+ and indomethacin
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
1.1.1.188
0.00039
-
-
Homo sapiens
Mefenamic acid
1.1.1.188
0.0004
-
-
Homo sapiens
4-carboxy-2',4'-dinitrodiphenylamine
1.1.1.188
0.0007
-
-
Homo sapiens
Meclofenamic acid
1.1.1.188
0.0014
-
-
Homo sapiens
naproxen
1.1.1.188
0.0015
-
-
Homo sapiens
4-chloro-N-(4-tolyl)-anthranilic acid
1.1.1.188
0.002
-
-
Homo sapiens
4-benzoyl-benzoic acid
1.1.1.188
0.002
-
-
Homo sapiens
4-nitro-N-phenylanthranilic acid
1.1.1.188
0.0023
-
-
Homo sapiens
indomethacin
1.1.1.188
0.003
-
-
Homo sapiens
4-chloro-N-phenylanthranilic acid
1.1.1.188
0.0034
-
-
Homo sapiens
sulindac
1.1.1.188
0.0078
-
-
Homo sapiens
flurbiprofen
1.1.1.188
0.0099
-
-
Homo sapiens
Ibuprofen
1.1.1.188
0.011
-
-
Homo sapiens
4-carboxy-2-aminodiphenylamine
1.1.1.188
0.011
-
-
Homo sapiens
5-methyl-N-phenylanthranilic acid
1.1.1.188
0.04
-
-
Homo sapiens
Zomepirac
1.1.1.188
0.77
-
-
Homo sapiens
salicylic acid
1.1.1.188
1.2
-
-
Homo sapiens
aspirin
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
1.1.1.188
4-benzoyl-benzoic acid
-
Homo sapiens
1.1.1.188
4-carboxy-2',4'-dinitrodiphenylamine
-
Homo sapiens
1.1.1.188
4-carboxy-2-aminodiphenylamine
-
Homo sapiens
1.1.1.188
4-chloro-N-(4-tolyl)-anthranilic acid
-
Homo sapiens
1.1.1.188
4-chloro-N-phenylanthranilic acid
-
Homo sapiens
1.1.1.188
4-nitro-N-phenylanthranilic acid
-
Homo sapiens
1.1.1.188
5-methyl-N-phenylanthranilic acid
-
Homo sapiens
1.1.1.188
aspirin
-
Homo sapiens
1.1.1.188
flurbiprofen
-
Homo sapiens
1.1.1.188
Ibuprofen
-
Homo sapiens
1.1.1.188
indomethacin
-
Homo sapiens
1.1.1.188
indomethacin
inhibits AKR1C3, but does not inhibit highly related AKR1C1 or AKR1C2
Homo sapiens
1.1.1.188
Meclofenamic acid
-
Homo sapiens
1.1.1.188
Mefenamic acid
-
Homo sapiens
1.1.1.188
additional information
AKR1C3 is potently inhibited by non-steroidal anti-inflammatory drugs, which are protective against breast cancer
Homo sapiens
1.1.1.188
N-(4-chlorobenzoyl)-melatonin
exhibits uncompetitive inhibition patterns for the reduction of 9,10-phenanthrenequinone but competitive inhibition patterns for the reduction of androstenedione by AKR1C3
Homo sapiens
1.1.1.188
naproxen
-
Homo sapiens
1.1.1.188
salicylic acid
-
Homo sapiens
1.1.1.188
sulindac
-
Homo sapiens
1.1.1.188
Zomepirac
-
Homo sapiens
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.1.1.188
0.0003
-
Mefenamic acid
-
Homo sapiens
1.1.1.188
0.00038
-
4-carboxy-2',4'-dinitrodiphenylamine
-
Homo sapiens
1.1.1.188
0.0014
-
4-chloro-N-(4-tolyl)-anthranilic acid
-
Homo sapiens
1.1.1.188
0.0019
-
4-benzoyl-benzoic acid
-
Homo sapiens
1.1.1.188
0.0019
-
4-nitro-N-phenylanthranilic acid
-
Homo sapiens
1.1.1.188
0.0029
-
4-chloro-N-phenylanthranilic acid
-
Homo sapiens
1.1.1.188
0.0034
-
N-(4-chlorobenzoyl)-melatonin
-
Homo sapiens
1.1.1.188
0.0073
-
5-methyl-N-phenylanthranilic acid
-
Homo sapiens
1.1.1.188
0.01
-
4-carboxy-2-aminodiphenylamine
-
Homo sapiens
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.1.188
breast
normal breast expresses very high levels of AKR1C3 relative to other tissues
Homo sapiens
-
1.1.1.188
breast cancer cell
18fold increase in the median AKR1C3 mRNA levels in breast cancer patients as compared to those without disease
Homo sapiens
-
1.1.1.188
MCF-7 cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.188
9,10-phenanthrenequinone + NADPH + H+
-
697271
Homo sapiens
?
-
-
-
?
1.1.1.188
prostaglandin D2 + NADPH + H+
-
697271
Homo sapiens
9alpha,11beta-prostaglandin F2 + NADP+
-
-
-
?
1.1.1.188
prostaglandin H2 + NADPH + H+
-
697271
Homo sapiens
prostaglandin F2alpha + NADP+
-
-
-
?