BRENDA - Enzyme Database show

Structure-activity relationship for the first-in-class clinical steroid sulfatase inhibitor irosustat (STX64, BN83495)

Woo, L.W.; Ganeshapillai, D.; Thomas, M.P.; Sutcliffe, O.B.; Malini, B.; Mahon, M.F.; Purohit, A.; Potter, B.V.; ChemMedChem 6, 2019-2034 (2011)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
2-methoxy-6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
3-oxo-1,3-dihydro-2H-cyclobuta[c]chromen-6-yl sulfamate
-
Homo sapiens
3.1.6.2
4-oxo-1,2,3,4-tetrahydrocyclopenta[c]chromen-7-yl sulfamate
-
Homo sapiens
3.1.6.2
5-methyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-(3-phenylpropoxy)-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-(pentyloxy)-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-methoxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-5-(3-phenylpropyl)-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-5-pentyl-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17,18,19-tetradecahydrocyclopentadeca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydrocyclotrideca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13,14,15-decahydrocycloundeca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13-octahydrocyclonona[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-ylsulfamide
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-2-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl dimethylsulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-7,8,9,10,11,12,13,14,15,16-decahydro-6H-cyclododeca[c]-chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-7,8,9,10,11,12,13,14-octahydro-6H-cyclodeca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
estrone 3-O-sulfamate
-
Homo sapiens
3.1.6.2
irosustat
i.e. STX64, BN83495, structure-activity relationship study. The inhibitor is used in clinical trials for patients with advanced hormone-dependent cancer
Homo sapiens
3.1.6.2
additional information
evaluation of quinolin-2(1H)-one and quinoline derivatives of irosustat as enzyme inhibitors. N-(piperidino), N,N-(dibenzyl)sulfamate, and N,N-dimethyl derivatives of estrone 3-O-sulfamate are weak reversible or inactive inhibitors of the enzyme in placental microsomes. No inhibition by the N-benzoyl estrone 3-O-sulfamate variant 3-(benzyloxy)-8,9,10,11-tetrahydro-5H-cyclohepta[c]quinolin-6(7H)-one. Molecular modelling
Homo sapiens
3.1.6.2
N-acetylated estrone 3-O-sulfamate
inhibits the enzyme irreversibly, albeit much less potently than estrone 3-O-sulfamate
Homo sapiens
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.6.2
microsome
-
Homo sapiens
-
-
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.6.2
Homo sapiens
-
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
JEG-3 cell
choriocarcinoma cells
Homo sapiens
-
3.1.6.2
liver
-
Homo sapiens
-
3.1.6.2
placenta
-
Homo sapiens
-
3.1.6.2
skin
-
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
estrone sulfate + H2O
-
714750
Homo sapiens
estrone + sulfate
-
-
-
?
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
0.000000015
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13,14,15-decahydrocycloundeca[c]chromen-3-yl sulfamate
3.1.6.2
0.000000022
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13-octahydrocyclonona[c]chromen-3-yl sulfamate
3.1.6.2
0.000000025
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-7,8,9,10,11,12,13,14-octahydro-6H-cyclodeca[c]chromen-3-yl sulfamate
3.1.6.2
0.0000009
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl sulfamate
3.1.6.2
0.0000015
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
3.1.6.2
0.000007
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
4-oxo-1,2,3,4-tetrahydrocyclopenta[c]chromen-7-yl sulfamate
3.1.6.2
0.000032
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
3-oxo-1,3-dihydro-2H-cyclobuta[c]chromen-6-yl sulfamate
3.1.6.2
0.000078
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
2-methoxy-6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
3.1.6.2
0.0001
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-7,8,9,10,11,12,13,14,15,16-decahydro-6H-cyclododeca[c]-chromen-3-yl sulfamate
3.1.6.2
0.00022
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydrocyclotrideca[c]chromen-3-yl sulfamate
3.1.6.2
0.00024
-
pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
3.1.6.2
0.000283
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-2-yl sulfamate
3.1.6.2
0.001
-
above, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-ylsulfamide
3.1.6.2
0.0016
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17,18,19-tetradecahydrocyclopentadeca[c]chromen-3-yl sulfamate
3.1.6.2
0.0024
-
pH not specified in the publication, temperature not specified in the publication
Homo sapiens
5-methyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
3.1.6.2
0.01
-
above, in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl dimethylsulfamate
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
0.000000015
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13,14,15-decahydrocycloundeca[c]chromen-3-yl sulfamate
3.1.6.2
0.000000022
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13-octahydrocyclonona[c]chromen-3-yl sulfamate
3.1.6.2
0.000000025
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-7,8,9,10,11,12,13,14-octahydro-6H-cyclodeca[c]chromen-3-yl sulfamate
3.1.6.2
0.0000009
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl sulfamate
3.1.6.2
0.0000015
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
3.1.6.2
0.000007
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
4-oxo-1,2,3,4-tetrahydrocyclopenta[c]chromen-7-yl sulfamate
3.1.6.2
0.000032
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
3-oxo-1,3-dihydro-2H-cyclobuta[c]chromen-6-yl sulfamate
3.1.6.2
0.000078
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
2-methoxy-6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
3.1.6.2
0.0001
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-7,8,9,10,11,12,13,14,15,16-decahydro-6H-cyclododeca[c]-chromen-3-yl sulfamate
3.1.6.2
0.00022
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydrocyclotrideca[c]chromen-3-yl sulfamate
3.1.6.2
0.00024
-
pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
3.1.6.2
0.000283
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-2-yl sulfamate
3.1.6.2
0.001
-
above, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-ylsulfamide
3.1.6.2
0.0016
-
in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17,18,19-tetradecahydrocyclopentadeca[c]chromen-3-yl sulfamate
3.1.6.2
0.0024
-
pH not specified in the publication, temperature not specified in the publication
Homo sapiens
5-methyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
3.1.6.2
0.01
-
above, in JEG-3 cells, pH not specified in the publication, temperature not specified in the publication
Homo sapiens
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl dimethylsulfamate
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
2-methoxy-6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
3-oxo-1,3-dihydro-2H-cyclobuta[c]chromen-6-yl sulfamate
-
Homo sapiens
3.1.6.2
4-oxo-1,2,3,4-tetrahydrocyclopenta[c]chromen-7-yl sulfamate
-
Homo sapiens
3.1.6.2
5-methyl-6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-(3-phenylpropoxy)-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-(pentyloxy)-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-methoxy-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-5-(3-phenylpropyl)-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-5-pentyl-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17,18,19-tetradecahydrocyclopentadeca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydrocyclotrideca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13,14,15-decahydrocycloundeca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11,12,13-octahydrocyclonona[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[c]quinolin-3-ylsulfamide
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-2-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl dimethylsulfamate
-
Homo sapiens
3.1.6.2
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-7,8,9,10,11,12,13,14,15,16-decahydro-6H-cyclododeca[c]-chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-7,8,9,10,11,12,13,14-octahydro-6H-cyclodeca[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
6-oxo-7,8,9,10-tetrahydro-6H-benzo[c]chromen-3-yl sulfamate
-
Homo sapiens
3.1.6.2
estrone 3-O-sulfamate
-
Homo sapiens
3.1.6.2
irosustat
i.e. STX64, BN83495, structure-activity relationship study. The inhibitor is used in clinical trials for patients with advanced hormone-dependent cancer
Homo sapiens
3.1.6.2
additional information
evaluation of quinolin-2(1H)-one and quinoline derivatives of irosustat as enzyme inhibitors. N-(piperidino), N,N-(dibenzyl)sulfamate, and N,N-dimethyl derivatives of estrone 3-O-sulfamate are weak reversible or inactive inhibitors of the enzyme in placental microsomes. No inhibition by the N-benzoyl estrone 3-O-sulfamate variant 3-(benzyloxy)-8,9,10,11-tetrahydro-5H-cyclohepta[c]quinolin-6(7H)-one. Molecular modelling
Homo sapiens
3.1.6.2
N-acetylated estrone 3-O-sulfamate
inhibits the enzyme irreversibly, albeit much less potently than estrone 3-O-sulfamate
Homo sapiens
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.6.2
microsome
-
Homo sapiens
-
-
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
JEG-3 cell
choriocarcinoma cells
Homo sapiens
-
3.1.6.2
liver
-
Homo sapiens
-
3.1.6.2
placenta
-
Homo sapiens
-
3.1.6.2
skin
-
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
estrone sulfate + H2O
-
714750
Homo sapiens
estrone + sulfate
-
-
-
?