BRENDA - Enzyme Database show

Chiral aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole template: synthesis, absolute configuration, and in vitro activity

Wood, P.M.; Woo, L.W.; Labrosse, J.R.; Trusselle, M.N.; Abbate, S.; Longhi, G.; Castiglioni, E.; Lebon, F.; Purohit, A.; Reed, M.J.; Potter, B.V.; J. Med. Chem. 51, 4226-4238 (2008)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
(R)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
pure R(+)-enantiomer of 1-[(4-Cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Homo sapiens
3.1.6.2
(S)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
pure S(-)-enantiomer of 1-[(4-Cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Homo sapiens
3.1.6.2
1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
bromo derivative of 1-[(4-cyanophenyl)(3-chloro-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole does improve aromatase inhibitory activity
Homo sapiens
3.1.6.2
1-[(4-cyanophenyl)(3-chloro-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
meta-chloro derivative of 1-[(4-cyanophenyl)(4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole does increase aromatase inhibition activity
Homo sapiens
3.1.6.2
1-[(4-cyanophenyl)(4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
increase of aromatase inhibitory activity due to presence of a para-cyanophenyl moiety
Homo sapiens
3.1.6.2
1-[bis-(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
best dual inhibition
Homo sapiens
3.1.6.2
1-[bis-(3-sulfamoyloxy-4-methoxyphenyl)methyl]-1H-[1,2,4]triazole
methoxy groups reduce inhibition of aromatase compared to 1-[bis-(3-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Homo sapiens
3.1.6.2
1-[bis-(3-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
sulfamate in meta-position increases aromatase inhibition strength compared to para-position
Homo sapiens
3.1.6.2
1-[bis-(4-sulfamoyloxy-3-methoxyphenyl)methyl]-1H-[1,2,4]triazole
exchange in positions of methoxy and sulfamate group compared to 1-[bis-(3-sulfamoyloxy-4-methoxyphenyl)methyl]-1H-[1,2,4]triazole fails to improve aromatase inhibitory activity
Homo sapiens
3.1.6.2
STX64
synonym BN83495, irreversible inhibition, STS inhibitor property within dual aromatase-sulfatase inhibitor, letrozole reversible cytochrome P450 enzyme aromatase inhibitor serves as aromatase inhibiting component
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.1.6.2
dehydroepiandrosterone sulfate + H2O
Homo sapiens
-
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol, an androgen with estrogenic properties, stimulating breast cancer growth
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
in breast cancer tissue 10 times more estrone originates from estrone sulfate than from androstenedione
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.6.2
Homo sapiens
P08842
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
JEG-3 cell
choriocarcinoma cell line in monolayer
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
693555
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol, an androgen with estrogenic properties, stimulating breast cancer growth
-
-
?
3.1.6.2
estrone sulfate + H2O
-
693555
Homo sapiens
estrone + sulfate
in breast cancer tissue 10 times more estrone originates from estrone sulfate than from androstenedione
-
-
?
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
additional information
-
at 10 microM 21.5% inhibition of STS activity in JEG-3 cells, IC50 for aromatase = 0.000013 mM
Homo sapiens
1-[(4-cyanophenyl)(4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
additional information
-
at 10 microM 10.9% inhibition of STS activity in JEG-3 cells, 40% inhibition of aromatase
Homo sapiens
1-[bis-(3-sulfamoyloxy-4-methoxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
additional information
-
at 10 microM 31.4% inhibition of STS activity in JEG-3 cells, IC50 for aromatase = 0.000099 mM
Homo sapiens
1-[bis-(3-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
additional information
-
at 10 microM 11.9% inhibition of STS activity in JEG-3 cells, 33% inhibition of aromatase
Homo sapiens
1-[bis-(4-sulfamoyloxy-3-methoxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.0000015
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.0003 mM
Homo sapiens
STX64
3.1.6.2
0.000476
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.000043 mM
Homo sapiens
1-[bis-(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.000553
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.0000143 mM
Homo sapiens
(S)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.00092
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.000012 mM
Homo sapiens
1-[(4-cyanophenyl)(3-chloro-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.0026
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.000003 mM
Homo sapiens
1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.004633
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.0000032 mM
Homo sapiens
(R)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
additional information
-
at 10 microM 21.5% inhibition of STS activity in JEG-3 cells, IC50 for aromatase = 0.000013 mM
Homo sapiens
1-[(4-cyanophenyl)(4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
additional information
-
at 10 microM 10.9% inhibition of STS activity in JEG-3 cells, 40% inhibition of aromatase
Homo sapiens
1-[bis-(3-sulfamoyloxy-4-methoxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
additional information
-
at 10 microM 31.4% inhibition of STS activity in JEG-3 cells, IC50 for aromatase = 0.000099 mM
Homo sapiens
1-[bis-(3-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
additional information
-
at 10 microM 11.9% inhibition of STS activity in JEG-3 cells, 33% inhibition of aromatase
Homo sapiens
1-[bis-(4-sulfamoyloxy-3-methoxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.0000015
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.0003 mM
Homo sapiens
STX64
3.1.6.2
0.000476
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.000043 mM
Homo sapiens
1-[bis-(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.000553
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.0000143 mM
Homo sapiens
(S)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.00092
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.000012 mM
Homo sapiens
1-[(4-cyanophenyl)(3-chloro-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.0026
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.000003 mM
Homo sapiens
1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
3.1.6.2
0.004633
-
enzyme activity in JEG-3 cells, IC50 for aromatase = 0.0000032 mM
Homo sapiens
(R)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
(R)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
pure R(+)-enantiomer of 1-[(4-Cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Homo sapiens
3.1.6.2
(S)-1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
pure S(-)-enantiomer of 1-[(4-Cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Homo sapiens
3.1.6.2
1-[(4-cyanophenyl)(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
bromo derivative of 1-[(4-cyanophenyl)(3-chloro-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole does improve aromatase inhibitory activity
Homo sapiens
3.1.6.2
1-[(4-cyanophenyl)(3-chloro-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
meta-chloro derivative of 1-[(4-cyanophenyl)(4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole does increase aromatase inhibition activity
Homo sapiens
3.1.6.2
1-[(4-cyanophenyl)(4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
increase of aromatase inhibitory activity due to presence of a para-cyanophenyl moiety
Homo sapiens
3.1.6.2
1-[bis-(3-bromo-4-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
best dual inhibition
Homo sapiens
3.1.6.2
1-[bis-(3-sulfamoyloxy-4-methoxyphenyl)methyl]-1H-[1,2,4]triazole
methoxy groups reduce inhibition of aromatase compared to 1-[bis-(3-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
Homo sapiens
3.1.6.2
1-[bis-(3-sulfamoyloxyphenyl)methyl]-1H-[1,2,4]triazole
sulfamate in meta-position increases aromatase inhibition strength compared to para-position
Homo sapiens
3.1.6.2
1-[bis-(4-sulfamoyloxy-3-methoxyphenyl)methyl]-1H-[1,2,4]triazole
exchange in positions of methoxy and sulfamate group compared to 1-[bis-(3-sulfamoyloxy-4-methoxyphenyl)methyl]-1H-[1,2,4]triazole fails to improve aromatase inhibitory activity
Homo sapiens
3.1.6.2
STX64
synonym BN83495, irreversible inhibition, STS inhibitor property within dual aromatase-sulfatase inhibitor, letrozole reversible cytochrome P450 enzyme aromatase inhibitor serves as aromatase inhibiting component
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.1.6.2
dehydroepiandrosterone sulfate + H2O
Homo sapiens
-
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol, an androgen with estrogenic properties, stimulating breast cancer growth
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
in breast cancer tissue 10 times more estrone originates from estrone sulfate than from androstenedione
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
JEG-3 cell
choriocarcinoma cell line in monolayer
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
693555
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol, an androgen with estrogenic properties, stimulating breast cancer growth
-
-
?
3.1.6.2
estrone sulfate + H2O
-
693555
Homo sapiens
estrone + sulfate
in breast cancer tissue 10 times more estrone originates from estrone sulfate than from androstenedione
-
-
?