BRENDA - Enzyme Database show

Anticancer steroid sulfatase inhibitors: synthesis of a potent fluorinated second-generation agent, in vitro and in vivo activities, molecular modeling, and protein crystallography

Woo, L.W.; Fischer, D.S.; Sharland, C.M.; Trusselle, M.; Foster, P.A.; Chander, S.K.; Di Fiore, A.; Supuran, C.T.; De Simone, G.; Purohit, A.; Reed, M.J.; Potter, B.V.; Mol. Cancer Ther. 7, 2435-2444 (2008)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 48% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 5, day 17: 50% recovery, day 28: complete recovery
Homo sapiens
3.1.6.2
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 48% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 5, day 17: 50% recovery, day 28: complete recovery
Rattus norvegicus
3.1.6.2
STX213
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 25% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 4, day 12: 50% recovery, day 15: almost complete recovery
Homo sapiens
3.1.6.2
STX213
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 25% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 4, day 12: 50% recovery, day 15: almost complete recovery
Rattus norvegicus
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
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
Rattus norvegicus
-
dehydroepiandrosterone + sulfate
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
?
3.1.6.2
estrone sulfate + H2O
Rattus norvegicus
-
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.6.2
Homo sapiens
P08842
-
-
3.1.6.2
Rattus norvegicus
-
female adult Wistar rats
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
JEG-3 cell
choriocarcinoma cell line
Homo sapiens
-
3.1.6.2
liver
-
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
-
694116
Homo sapiens
dehydroepiandrosterone + sulfate
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
694116
Rattus norvegicus
dehydroepiandrosterone + sulfate
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
-
?
3.1.6.2
estrone sulfate + H2O
-
694116
Homo sapiens
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
-
?
3.1.6.2
estrone sulfate + H2O
-
694116
Rattus norvegicus
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
-
?
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
0.000000035
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000003 mM
Homo sapiens
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
3.1.6.2
0.000000035
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000003 mM
Rattus norvegicus
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
3.1.6.2
0.00000018
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000005 mM
Homo sapiens
STX213
3.1.6.2
0.00000018
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000005 mM
Rattus norvegicus
STX213
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
3.1.6.2
0.000000035
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000003 mM
Homo sapiens
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
3.1.6.2
0.000000035
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000003 mM
Rattus norvegicus
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
3.1.6.2
0.00000018
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000005 mM
Homo sapiens
STX213
3.1.6.2
0.00000018
-
in vitro JEG-3 cells: 0.001-10000 nmol/l inhibitor and incubation with estrone-3-sulfate, IC50 for human carbonic anhydrase II = 0.000005 mM
Rattus norvegicus
STX213
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.6.2
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 48% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 5, day 17: 50% recovery, day 28: complete recovery
Homo sapiens
3.1.6.2
3-sulfamoyloxy-N-3,3,3-trifluoropropyl-16,17-seco-estra-1,3,4(10)-triene-16,17-imide
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 48% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 5, day 17: 50% recovery, day 28: complete recovery
Rattus norvegicus
3.1.6.2
STX213
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 25% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 4, day 12: 50% recovery, day 15: almost complete recovery
Homo sapiens
3.1.6.2
STX213
highly potent, long-acting, nonestrogenic steroid sulfatase inhibitor with inhibitory properties to human carbonic anhydrase II, thus enabling transport by erythorcytes, no estrogenic effects observed in uterine weight gain study with ovariectomized Wistar rats, 24 h after last dose of 4 days of oral administration of 10 mg/kg/d, in vivo: single dose of 0.1 mg/kg 25% inhibition of liver steroid sulfatase activity, 0.5 and 1 mg/kg total inhibition, activity measured 24 h after dose administration, recovery of steroid sulfatase acitivity after single oral dose of 10 mg/kg: complete inhibition till day 4, day 12: 50% recovery, day 15: almost complete recovery
Rattus norvegicus
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
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
Rattus norvegicus
-
dehydroepiandrosterone + sulfate
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
?
3.1.6.2
estrone sulfate + H2O
Homo sapiens
-
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
?
3.1.6.2
estrone sulfate + H2O
Rattus norvegicus
-
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.6.2
JEG-3 cell
choriocarcinoma cell line
Homo sapiens
-
3.1.6.2
liver
-
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
-
694116
Homo sapiens
dehydroepiandrosterone + sulfate
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
-
?
3.1.6.2
dehydroepiandrosterone sulfate + H2O
-
694116
Rattus norvegicus
dehydroepiandrosterone + sulfate
conversion to androstenediol by 17beta-hydroxysteroid dehydrogenase type 1, androstenediol supports mammary tumor growth in rodents, or conversion to androstenedione, main substrate for aromatase in postmenopausal women
-
-
?
3.1.6.2
estrone sulfate + H2O
-
694116
Homo sapiens
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
-
?
3.1.6.2
estrone sulfate + H2O
-
694116
Rattus norvegicus
estrone + sulfate
conversion to estradiol by 17beta-hydroxysteroid dehydrogenase type 1
-
-
?