BRENDA - Enzyme Database show

The development of steroid sulfatase inhibitors for hormone-dependent cancer therapy

Day, J.M.; Purohit, A.; Tutill, H.J.; Foster, P.A.; Woo, L.W.; Potter, B.V.; Reed, M.J.; Ann. N. Y. Acad. Sci. 1155, 80-87 (2009)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
STX213
phenol sulfamate pharmacophore, irreversible total inhibition from 10-1000 nM in Ishikawa cells, in vivo: upon administration of 1 mg/kg body mass/day reduced tumor growth over 28-day period in transplanted Ishikawa cells in MF-1 nude ovariectomized mice in the presence of estradiol sulfate (prerequisite for tumor cell development in ovariectomized mice), abolished liver STS activity, and reduced plasma estradiol levels
Homo sapiens
3.1.6.2
STX64
synonym BN83495, phenol sulfamate pharmacophore, irreversible STS inhibition from 10-1000 nM in Ishikawa cells, irreversible inhibition in OVCAR-3 ovarian cancer cells and JEG-3 choriocarcionoma cells at 10µM, irreversible inhibition from 10-1000 nM in LNCaP prostate cancer cells, in vivo: upon administration of 1 mg/kg body mass/day reduced tumor growth over 28-day period in transplanted Ishikawa cells in MF-1 nude ovariectomized mice in the presence of estradiol sulfate (prerequisite for tumor cell development in ovariectomized mice), abolished liver STS activity, and reduced plasma estradiol levels
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 andgrogen testosterone or androstenediol, androgens stimulate growth of prostate cancer cells
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
subsequent conversion to biologically active estrogen estradiol, increased activity and expression of STS in hormone-dependent cancer cells, estradiol prerequisite for Ishikawa cell tumorgenesis in ovariectomized mouse model, estrogens are suggested as growth stimulators in prostate cancer cells as well
-
?
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
HEK-293-EBNA cell
human embryonic kidney carcinoma cell line
Homo sapiens
-
3.1.6.2
Ishikawa cell
human endometrial adenocarcinoma cell culture, human Ishikawa cells transplanted into MF-1 ovariectomized naked mouse model
Homo sapiens
-
3.1.6.2
JEG-3 cell
choriocarcinoma cell line
Homo sapiens
-
3.1.6.2
LNCaP cell
human prostate cancer cells with mutated androgen receptor, as is typical for many human prostate tumors
Homo sapiens
-
3.1.6.2
MCF-7 cell
breast cancer cell line
Homo sapiens
-
3.1.6.2
OVCAR-3 cell
human ovarian cancer cell line
Homo sapiens
-
Specific Activity [micromol/min/mg]
EC Number
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
3.1.6.2
additional information
-
STS activity in 86% of human endometrial cancer tissue, 26% in normal endometrial tissue in 26%, confirmed by immunohistochemistry, STS acitivity in MCF-7 breast cancer cells about 20 fmol/20 h/million cells, STS acitivity in Ishikawa endometrial cancer cells 39.4 fmol/20 h/million cells, STS acitivity in LNCaP prostate cancer cells 41.5 fmol/20 h/million cells, STS acitivity in OVCAR-3 ovarian cancer cells 127.4 fmol/20 h/million cells
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
-
690441
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to andgrogen testosterone or androstenediol, androgens stimulate growth of prostate cancer cells
-
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
690441
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to testosterone
-
-
?
3.1.6.2
estrone sulfate + H2O
-
690441
Homo sapiens
estrone + sulfate
subsequent conversion to biologically active estrogen estradiol, increased activity and expression of STS in hormone-dependent cancer cells, estradiol prerequisite for Ishikawa cell tumorgenesis in ovariectomized mouse model, estrogens are suggested as growth stimulators in prostate cancer cells as well
-
-
?
3.1.6.2
estrone sulfate + H2O
-
690441
Homo sapiens
estrone + sulfate
subsequent conversion to estradiol
-
-
?
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
STX213
phenol sulfamate pharmacophore, irreversible total inhibition from 10-1000 nM in Ishikawa cells, in vivo: upon administration of 1 mg/kg body mass/day reduced tumor growth over 28-day period in transplanted Ishikawa cells in MF-1 nude ovariectomized mice in the presence of estradiol sulfate (prerequisite for tumor cell development in ovariectomized mice), abolished liver STS activity, and reduced plasma estradiol levels
Homo sapiens
3.1.6.2
STX64
synonym BN83495, phenol sulfamate pharmacophore, irreversible STS inhibition from 10-1000 nM in Ishikawa cells, irreversible inhibition in OVCAR-3 ovarian cancer cells and JEG-3 choriocarcionoma cells at 10µM, irreversible inhibition from 10-1000 nM in LNCaP prostate cancer cells, in vivo: upon administration of 1 mg/kg body mass/day reduced tumor growth over 28-day period in transplanted Ishikawa cells in MF-1 nude ovariectomized mice in the presence of estradiol sulfate (prerequisite for tumor cell development in ovariectomized mice), abolished liver STS activity, and reduced plasma estradiol levels
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 andgrogen testosterone or androstenediol, androgens stimulate growth of prostate cancer cells
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
subsequent conversion to biologically active estrogen estradiol, increased activity and expression of STS in hormone-dependent cancer cells, estradiol prerequisite for Ishikawa cell tumorgenesis in ovariectomized mouse model, estrogens are suggested as growth stimulators in prostate cancer cells as well
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
HEK-293-EBNA cell
human embryonic kidney carcinoma cell line
Homo sapiens
-
3.1.6.2
Ishikawa cell
human endometrial adenocarcinoma cell culture, human Ishikawa cells transplanted into MF-1 ovariectomized naked mouse model
Homo sapiens
-
3.1.6.2
JEG-3 cell
choriocarcinoma cell line
Homo sapiens
-
3.1.6.2
LNCaP cell
human prostate cancer cells with mutated androgen receptor, as is typical for many human prostate tumors
Homo sapiens
-
3.1.6.2
MCF-7 cell
breast cancer cell line
Homo sapiens
-
3.1.6.2
OVCAR-3 cell
human ovarian cancer cell line
Homo sapiens
-
Specific Activity [micromol/min/mg] (protein specific)
EC Number
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
3.1.6.2
additional information
-
STS activity in 86% of human endometrial cancer tissue, 26% in normal endometrial tissue in 26%, confirmed by immunohistochemistry, STS acitivity in MCF-7 breast cancer cells about 20 fmol/20 h/million cells, STS acitivity in Ishikawa endometrial cancer cells 39.4 fmol/20 h/million cells, STS acitivity in LNCaP prostate cancer cells 41.5 fmol/20 h/million cells, STS acitivity in OVCAR-3 ovarian cancer cells 127.4 fmol/20 h/million cells
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
-
690441
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to andgrogen testosterone or androstenediol, androgens stimulate growth of prostate cancer cells
-
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
690441
Homo sapiens
dehydroepiandrosterone + sulfate
subsequent conversion to testosterone
-
-
?
3.1.6.2
estrone sulfate + H2O
-
690441
Homo sapiens
estrone + sulfate
subsequent conversion to biologically active estrogen estradiol, increased activity and expression of STS in hormone-dependent cancer cells, estradiol prerequisite for Ishikawa cell tumorgenesis in ovariectomized mouse model, estrogens are suggested as growth stimulators in prostate cancer cells as well
-
-
?
3.1.6.2
estrone sulfate + H2O
-
690441
Homo sapiens
estrone + sulfate
subsequent conversion to estradiol
-
-
?