Literature summary for 3.1.6.2 extracted from

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

Inhibitors

Inhibitors	Comment	Organism
STX64	strong STS inhibitor with phenol sulfamate pharmacophore, basis for STS inhibition in dual inhibitors in scaffold of aromatase inhibitor YM511	Homo sapiens
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
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	?
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	?
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	?
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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Rattus norvegicus	-	immature female Wistar rats	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
blood plasma	plasma estradiol levels are stimulated 3 days ahead of inhibitor application with pregnant mare's serum gonadotropin (PMSG)	Rattus norvegicus	-
JEG-3 cell	human choriocarcinoma cells	Homo sapiens	-
liver	liver STS activitiy	Rattus norvegicus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
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	?
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	?
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	?
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	?

Synonyms

Synonyms	Comment	Organism
steroid sulfatase	-	Homo sapiens
steroid sulfatase	-	Rattus norvegicus
STS	-	Homo sapiens
STS	-	Rattus norvegicus

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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