BRENDA - Enzyme Database show

Synthesis of aromatase inhibitors and dual aromatase steroid sulfatase inhibitors by linking an arylsulfamate motif to 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile: SAR, crystal structures, in vitro and in vivo activities

Bubert, C.; Woo, L.W.; Sutcliffe, O.B.; Mahon, M.F.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V.; ChemMedChem 3, 1708-1730 (2008)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
STX64
strong STS inhibitor with phenol sulfamate pharmacophore, basis for STS inhibition in dual inhibitors in scaffold of aromatase inhibitor YM511
Homo sapiens
3.1.6.2
sulfamic acid 2-bromo-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-bromo-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethylsulfanyl)phenyl ester
thioether linker based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethylsulfanyl)phenyl ester
based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold, best dual inhibition performance in vivo in female Wistar rats: inhibition 3 h after single oral dose of 10 mg/kg body mass: 92% for aromatase, 98% for STS
Rattus norvegicus
3.1.6.2
sulfamic acid 2-chloro-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 3-(((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)methylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 3-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(((4-cyanophenyl)-(1,2,4)triazol-4-ylamino)methylsulfanyl)phenyl ester
thioether linker, , based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold, best STS inhibitor of tested dual inhibitor compounds
Homo sapiens
3.1.6.2
sulfamic acid 4-((2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)methylsulfamoyl)phenyl ester
N-methylated sulfonamide linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(10-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)decylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)phenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanylmethyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)-2-fluorophenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-propyl)-2-fluorophenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propylsulfanyl)phenyl ester
based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold, dual inhibition performance in vivo in female Wistar rats: inhibition 3 h after single oral dose of 10 mg/kg body mass: 82% for aromatase, 85% for STS
Rattus norvegicus
3.1.6.2
sulfamic acid 4-(5-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)pentylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
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 (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
Rattus norvegicus
-
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
?
3.1.6.2
estrone sulfate + H2O
Rattus norvegicus
-
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.6.2
Homo sapiens
-
-
-
3.1.6.2
Rattus norvegicus
-
immature female Wistar rats
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
blood plasma
plasma estradiol levels are stimulated 3 days ahead of inhibitor application with pregnant mare's serum gonadotropin (PMSG)
Rattus norvegicus
-
3.1.6.2
JEG-3 cell
human choriocarcinoma cells
Homo sapiens
-
3.1.6.2
liver
liver STS activitiy
Rattus norvegicus
-
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
-
691817
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
691817
Rattus norvegicus
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
-
?
3.1.6.2
estrone sulfate + H2O
-
691817
Homo sapiens
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
-
?
3.1.6.2
estrone sulfate + H2O
-
691817
Rattus norvegicus
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
-
?
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
0.0000015
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0003 mM
Homo sapiens
STX64
3.1.6.2
0.0009
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000055 mM, best STS inhibitor of tested dual inhibitors
Homo sapiens
sulfamic acid 4-(((4-cyanophenyl)-(1,2,4)triazol-4-ylamino)methylsulfanyl)phenyl ester
3.1.6.2
0.001
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000073 mM
Homo sapiens
sulfamic acid 4-(5-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)pentylsulfanyl)phenyl ester
3.1.6.2
0.0012
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000045 mM
Homo sapiens
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethylsulfanyl)phenyl ester
3.1.6.2
0.0015
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000017 mM
Homo sapiens
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
3.1.6.2
0.0015
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000021 mM
Homo sapiens
sulfamic acid 2-chloro-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
3.1.6.2
0.0016
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000025 mM
Homo sapiens
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-propyl)-2-fluorophenyl ester
3.1.6.2
0.0019
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000055 mM
Homo sapiens
sulfamic acid 4-(10-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)decylsulfanyl)phenyl ester
3.1.6.2
0.0026
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.000002 mM
Homo sapiens
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)-2-fluorophenyl ester
3.1.6.2
0.0035
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000039 mM
Homo sapiens
sulfamic acid 3-(((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)methylsulfanyl)phenyl ester
3.1.6.2
0.0055
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000015 mM
Homo sapiens
sulfamic acid 2-bromo-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
3.1.6.2
0.0061
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.000001 mM
Homo sapiens
sulfamic acid 2-bromo-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000017 mM
Homo sapiens
sulfamic acid 3-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00001 mM
Homo sapiens
sulfamic acid 4-((2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)methylsulfamoyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000021 mM
Homo sapiens
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000037 mM
Homo sapiens
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanylmethyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000089 mM
Homo sapiens
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
3.1.6.2
0.01
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 larger than 0.01 mM, IC50 for aromatase = 0.00000051 mM
Homo sapiens
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propylsulfanyl)phenyl ester
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
0.0000015
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0003 mM
Homo sapiens
STX64
3.1.6.2
0.0009
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000055 mM, best STS inhibitor of tested dual inhibitors
Homo sapiens
sulfamic acid 4-(((4-cyanophenyl)-(1,2,4)triazol-4-ylamino)methylsulfanyl)phenyl ester
3.1.6.2
0.001
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000073 mM
Homo sapiens
sulfamic acid 4-(5-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)pentylsulfanyl)phenyl ester
3.1.6.2
0.0012
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000045 mM
Homo sapiens
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethylsulfanyl)phenyl ester
3.1.6.2
0.0015
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000017 mM
Homo sapiens
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
3.1.6.2
0.0015
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000021 mM
Homo sapiens
sulfamic acid 2-chloro-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
3.1.6.2
0.0016
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000025 mM
Homo sapiens
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-propyl)-2-fluorophenyl ester
3.1.6.2
0.0019
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000055 mM
Homo sapiens
sulfamic acid 4-(10-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)decylsulfanyl)phenyl ester
3.1.6.2
0.0026
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.000002 mM
Homo sapiens
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)-2-fluorophenyl ester
3.1.6.2
0.0035
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000039 mM
Homo sapiens
sulfamic acid 3-(((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)methylsulfanyl)phenyl ester
3.1.6.2
0.0055
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000015 mM
Homo sapiens
sulfamic acid 2-bromo-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
3.1.6.2
0.0061
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.000001 mM
Homo sapiens
sulfamic acid 2-bromo-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000017 mM
Homo sapiens
sulfamic acid 3-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00001 mM
Homo sapiens
sulfamic acid 4-((2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)methylsulfamoyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.0000021 mM
Homo sapiens
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000037 mM
Homo sapiens
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanylmethyl)phenyl ester
3.1.6.2
0.01
-
larger than 0.01 mM, inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 for aromatase = 0.00000089 mM
Homo sapiens
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
3.1.6.2
0.01
-
inhibition of STS activity in JEG-3 cells tested with concentrations of 0.001-10000 nmol/l, IC50 larger than 0.01 mM, IC50 for aromatase = 0.00000051 mM
Homo sapiens
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propylsulfanyl)phenyl ester
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
STX64
strong STS inhibitor with phenol sulfamate pharmacophore, basis for STS inhibition in dual inhibitors in scaffold of aromatase inhibitor YM511
Homo sapiens
3.1.6.2
sulfamic acid 2-bromo-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-bromo-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)phenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethylsulfanyl)phenyl ester
thioether linker based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 2-chloro-4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethylsulfanyl)phenyl ester
based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold, best dual inhibition performance in vivo in female Wistar rats: inhibition 3 h after single oral dose of 10 mg/kg body mass: 92% for aromatase, 98% for STS
Rattus norvegicus
3.1.6.2
sulfamic acid 2-chloro-4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 3-(((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)methylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 3-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(((4-cyanophenyl)-(1,2,4)triazol-4-ylamino)methylsulfanyl)phenyl ester
thioether linker, , based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold, best STS inhibitor of tested dual inhibitor compounds
Homo sapiens
3.1.6.2
sulfamic acid 4-((2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)methylsulfamoyl)phenyl ester
N-methylated sulfonamide linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(10-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)decylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethyl)phenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-ethylsulfanylmethyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(2-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)ethyl)-2-fluorophenyl ester
ethylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)-propyl)-2-fluorophenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propyl)phenyl ester
propylene linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
Homo sapiens
3.1.6.2
sulfamic acid 4-(3-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)propylsulfanyl)phenyl ester
based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold, dual inhibition performance in vivo in female Wistar rats: inhibition 3 h after single oral dose of 10 mg/kg body mass: 82% for aromatase, 85% for STS
Rattus norvegicus
3.1.6.2
sulfamic acid 4-(5-((4-cyanophenyl)-[1,2,4]triazol-4-ylamino)pentylsulfanyl)phenyl ester
thioether linker, based on phenol sulfamate pharmacophore (STS inhibition) incorporated into YM511 (aromatase inhibitor) scaffold
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 (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
Rattus norvegicus
-
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
?
3.1.6.2
estrone sulfate + H2O
Rattus norvegicus
-
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
blood plasma
plasma estradiol levels are stimulated 3 days ahead of inhibitor application with pregnant mare's serum gonadotropin (PMSG)
Rattus norvegicus
-
3.1.6.2
JEG-3 cell
human choriocarcinoma cells
Homo sapiens
-
3.1.6.2
liver
liver STS activitiy
Rattus norvegicus
-
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
-
691817
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
691817
Rattus norvegicus
dehydroepiandrosterone + sulfate
subsequent conversion to androst-5-ene-3beta,17beta-diol (Adiol), an androgen with estrogenic properties, and thus a mitogen for the growth and development of hormome-dependent breast cancer
-
-
?
3.1.6.2
estrone sulfate + H2O
-
691817
Homo sapiens
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
-
?
3.1.6.2
estrone sulfate + H2O
-
691817
Rattus norvegicus
estrone + sulfate
estrogen estrone formed from androstenedione by cytochrome P450 enzyme aromatase, estrogen is a mitogen for growth and development of hormone-dependent breast cancer
-
-
?