Target Validation Information
Target ID T33489
Target Name Steryl-sulfatase
Target Type
Clinical Trial
Drug Potency against Target 2-ethylestradiol 3,17-O,O-bis-sulfamate Drug Info IC50 = 1000 nM [1]
Estradiol 3,17-O,O-bis-sulfamate Drug Info IC50 = 18 nM [1]
STX 64 Drug Info IC50 = 8 nM [2]
EMATE Drug Info IC50 = 80 nM [3]
2-(4-cyclohexylthiosemicarbazono)methyl-phenol Drug Info IC50 = 8000 nM [3]
2-methoxyestradiol 3,17-O,O-bis-sulfamate Drug Info IC50 = 39 nM [1]
Sulfamic acid 4-(2-hydroxy-benzoyl)-phenyl ester Drug Info IC50 = 4600 nM [4]
Sulfamic acid 3-(3-hydroxy-benzoyl)-phenyl ester Drug Info IC50 = 6900 nM [4]
4-Sulfamoyloxy-benzoic acid cyclooctyl ester Drug Info IC50 = 170 nM [5]
4-Sulfamoyloxy-benzoic acid heptyl ester Drug Info IC50 = 3400 nM [5]
4-Sulfamoyloxy-benzoic acid cyclohexyl ester Drug Info IC50 = 1700 nM [5]
4-Sulfamoyloxy-benzoic acid nonyl ester Drug Info IC50 = 4800 nM [5]
4-Sulfamoyloxy-benzoic acid cycloheptyl ester Drug Info IC50 = 500 nM [5]
4-Sulfamoyloxy-benzoic acid pentyl ester Drug Info IC50 = 5900 nM [5]
4-Sulfamoyloxy-benzoic acid octyl ester Drug Info IC50 = 5000 nM [5]
4-Sulfamoyloxy-benzoic acid cyclopentyl ester Drug Info IC50 = 9300 nM [5]
3-(4-cyclohexylthiosemicarbazono)methyl-phenol Drug Info IC50 = 4000 nM [3]
MHL cyclohexylthiosemicarbazone Drug Info IC50 = 460 nM [3]
3-{3-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate Drug Info IC50 = 3200 nM [4]
Sulfamic acid 3-benzoyl-phenyl ester Drug Info IC50 = 5700 nM [4]
3-{4-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate Drug Info IC50 = 780 nM [4]
Sulfamic acid 4-(3-methoxy-benzoyl)-phenyl ester Drug Info IC50 = 5200 nM [4]
Sulfamic acid 3-(3-methoxy-benzoyl)-phenyl ester Drug Info IC50 = 7100 nM [4]
Sulfamic acid 4-(2-methoxy-benzoyl)-phenyl ester Drug Info IC50 = 4800 nM [4]
2-methylsulfanylestradiol 3,17-O,O-bis-sulfamate Drug Info IC50 = 320 nM [1]
Sulfamic acid 3-(4-hydroxy-benzoyl)-phenyl ester Drug Info IC50 = 5000 nM [4]
2-Adamantan-2-ylidenemethyl-benzooxazol-6-ol Drug Info IC50 = 260 nM [6]
Sulfamic acid 2-nonyl-4-oxo-4H-chromen-6-yl ester Drug Info IC50 = 403 nM [7]
4-Sulfamoyloxy-benzoic acid propyl ester Drug Info IC50 = 13200 nM [5]
4-Sulfamoyloxy-benzoic acid hexyl ester Drug Info IC50 = 3800 nM [5]
4-(4-cyclohexylthiosemicarbazono)methyl-phenol Drug Info IC50 = 2300 nM [3]
Sulfamic acid 3-(4-methoxy-benzoyl)-phenyl ester Drug Info IC50 = 6900 nM [4]
Sulfamic acid 4-benzoyl-phenyl ester Drug Info IC50 = 5100 nM [4]
4-Sulfamoyloxy-benzoic acid butyl ester Drug Info IC50 = 10500 nM [5]
4-{4-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate Drug Info IC50 = 190 nM [8]
COUMATE Drug Info IC50 = 1.5 nM [9]
2',4'-dicyanobiphenyl-4-yl sulfamate Drug Info IC50 = 16.3 nM [9]
3-(4-hexylthiosemicarbazono)methyl-benzoic acid Drug Info IC50 = 12000 nM [3]
Action against Disease Model STX 64 The IC50 value of STX64, a potent STS inhibitor, against STS activity in JEG-3 cell line is 0.5 nmol/L. [10] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations The effects of modulating the murine steroid sulfatase axis pharmacologically (through administration of the substrate dehydroepiandrosterone sulfate [DHEAS], 0-40 mg/kg, or acute inhibition of the enzyme by CO uMATE, 10 mg/kg) or genetically (through loss of the gene in 39,X(Y)*O mice) were assayed using the 5-choice serial reaction time task (5-CSRTT) a test of visuospatial attention and response control, and a locomotor activity paradigm.HEAS administration improved 5-CSRTT performance under attentionally demanding conditions, whereas steroid sulfatase inhibition impaired accuracy under the same conditions. Loss of Sts expression constitutively throughout development in 39,X(Y)*O mice resulted in deficits in 5-CSRTT performance at short stimulus durations and reduced anticipatory responding. Neither the pharmacologic nor the genetic manipulations affected basic locomotor activity.These data provide converging evidence indicating a role for steroid sulfatase indiscrete aspects of attentional functioning and are suggestive of a role in motor impulsivity. The findings provide novel insights into the neurobiology of attention and strengthen the notion of STS as a candidate gene for the attentional component of ADHD [1]
References
REF 1J Med Chem. 2006 Dec 28;49(26):7683-96.2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity.
REF 2Potent active site-directed inhibition of steroid sulphatase by tricyclic coumarin-based sulphamates. Chem Biol. 2000 Oct;7(10):773-91.
REF 3J Med Chem. 2007 Jul 26;50(15):3661-6. Epub 2007 Jun 20.Thiosemicarbazones of formyl benzoic acids as novel potent inhibitors of estrone sulfatase.
REF 4Bioorg Med Chem Lett. 2002 Aug 19;12(16):2093-5.4,4'-Benzophenone-O,O'-disulfamate: a potent inhibitor of steroid sulfatase.
REF 5Bioorg Med Chem Lett. 2004 Feb 9;14(3):605-9.Inhibition of estrone sulfatase (ES) by alkyl and cycloalkyl ester derivatives of 4-[(aminosulfonyl)oxy] benzoic acid.
REF 6Bioorg Med Chem Lett. 2004 Oct 4;14(19):4999-5002.Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase.
REF 7J Med Chem. 2003 Nov 6;46(23):5091-4.Estrogenic potential of 2-alkyl-4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human steroid sulfatase.
REF 8J Med Chem. 2008 Jul 24;51(14):4226-38. Epub 2008 Jul 1.Chiral aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole template: synthesis, absolute configuration, and in vitro activity.
REF 9J Med Chem. 2010 Mar 11;53(5):2155-70.Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template.
REF 10A new therapeutic strategy against hormone-dependent breast cancer: the preclinical development of a dual aromatase and sulfatase inhibitor. Clin Cancer Res. 2008 Oct 15;14(20):6469-77. doi: 10.1158/1078-0432.CCR-08-1027.

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