Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHM0R1)

• DTT Name: Steryl-sulfatase (STS)
• Synonyms: Steryl-sulfate sulfohydrolase; Steroid sulfatase; STS; Estrone sulfatase; Arylsulfatase C; ASC
• Gene Name: STS
• DTT Type: Successful target; [1]
• BioChemical Class: Sulfuric ester hydrolase
• UniProt ID: STS_HUMAN
• TTD ID: T33489
• EC Number: EC 3.1.6.2
• Sequence:
  MPLRKMKIPFLLLFFLWEAESHAASRPNIILVMADDLGIGDPGCYGNKTIRTPNIDRLAS
  GGVKLTQHLAASPLCTPSRAAFMTGRYPVRSGMASWSRTGVFLFTASSGGLPTDEITFAK
  LLKDQGYSTALIGKWHLGMSCHSKTDFCHHPLHHGFNYFYGISLTNLRDCKPGEGSVFTT
  GFKRLVFLPLQIVGVTLLTLAALNCLGLLHVPLGVFFSLLFLAALILTLFLGFLHYFRPL
  NCFMMRNYEIIQQPMSYDNLTQRLTVEAAQFIQRNTETPFLLVLSYLHVHTALFSSKDFA
  GKSQHGVYGDAVEEMDWSVGQILNLLDELRLANDTLIYFTSDQGAHVEEVSSKGEIHGGS
  NGIYKGGKANNWEGGIRVPGILRWPRVIQAGQKIDEPTSNMDIFPTVAKLAGAPLPEDRI
  IDGRDLMPLLEGKSQRSDHEFLFHYCNAYLNAVRWHPQNSTSIWKAFFFTPNFNPVGSNG
  CFATHVCFCFGSYVTHHDPPLLFDISKDPRERNPLTPASEPRFYEILKVMQEAADRHTQT
  LPEVPDQFSWNNFLWKPWLQLCCPSTGLSCQCDREKQDKRLSR
• Function: Conversion of sulfated steroid precursors to estrogens during pregnancy.
• KEGG Pathway: Steroid hormone biosynthesis (hsa00140)
• Reactome Pathway: Glycosphingolipid metabolism (R-HSA-1660662)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tranilast	DME5Y64	Allergic rhinitis	CA08.0	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[2]
PGL-2	DMJTYO4	Endometriosis	GA10	Phase 2	[3]
PGL-2001	DMKA705	Endometriosis	GA10	Phase 2	[3]
STX-140	DMJK5CT	Osteoporosis	FB83.0	Phase 2	[4]
STX 64	DMJAPRK	Prostate cancer	2C82.0	Phase 1	[5]

40 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2',4'-dicyanobiphenyl-4-yl sulfamate	DM4QDZV	Discovery agent	N.A.	Investigative	[2]
2-(4-cyclohexylthiosemicarbazono)methyl-phenol	DMOH46C	Discovery agent	N.A.	Investigative	[6]
2-Adamantan-2-ylidenemethyl-benzooxazol-6-ol	DMXG029	Discovery agent	N.A.	Investigative	[7]
2-Amino-3-Oxo-4-Sulfo-Butyric Acid	DMXLZUA	Discovery agent	N.A.	Investigative	[8]
2-ethylestradiol 3,17-O,O-bis-sulfamate	DMC10DR	Discovery agent	N.A.	Investigative	[4]
2-methylsulfanylestradiol 3,17-O,O-bis-sulfamate	DMM4HXK	Discovery agent	N.A.	Investigative	[4]
3-(4-cyclohexylthiosemicarbazono)methyl-phenol	DMGQE8D	Discovery agent	N.A.	Investigative	[6]
3-(4-hexylthiosemicarbazono)methyl-benzoic acid	DMDYS7Q	Discovery agent	N.A.	Investigative	[6]
3-{3-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate	DMUH9PF	Discovery agent	N.A.	Investigative	[9]
3-{4-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate	DMGS2X7	Discovery agent	N.A.	Investigative	[9]
4-(4-cyclohexylthiosemicarbazono)methyl-phenol	DMSYH8R	Discovery agent	N.A.	Investigative	[6]
4-Sulfamoyloxy-benzoic acid butyl ester	DMWH2NT	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid cycloheptyl ester	DMDNRCU	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid cyclohexyl ester	DMIX0UN	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid cyclooctyl ester	DMG4LD9	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid cyclopentyl ester	DMF3C71	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid heptyl ester	DMTC25W	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid hexyl ester	DMU784M	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid nonyl ester	DM4Z7TU	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid octyl ester	DMQMSW3	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid pentyl ester	DMZIFW7	Discovery agent	N.A.	Investigative	[10]
4-Sulfamoyloxy-benzoic acid propyl ester	DMRILJC	Discovery agent	N.A.	Investigative	[10]
4-{4-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate	DMZUM95	Discovery agent	N.A.	Investigative	[11]
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[8]
Benzomate	DMRE96F	Discovery agent	N.A.	Investigative	[12]
EMATE	DMFQX1U	Discovery agent	N.A.	Investigative	[6]
Estradiol 17-O-sulfamate	DM7K14V	Discovery agent	N.A.	Investigative	[4]
Estradiol 3,17-O,O-bis-sulfamate	DMPM8I5	Discovery agent	N.A.	Investigative	[4]
MHL cyclohexylthiosemicarbazone	DMZ9MCR	Discovery agent	N.A.	Investigative	[6]
Nortropinyl-arylsulfonylurea 3	DMTY43L	Discovery agent	N.A.	Investigative	[13]
Sulfamic acid 2-nonyl-4-oxo-4H-chromen-6-yl ester	DMM70K1	Discovery agent	N.A.	Investigative	[14]
Sulfamic acid 3-(3-hydroxy-benzoyl)-phenyl ester	DMSZ50N	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 3-(3-methoxy-benzoyl)-phenyl ester	DMIQWAH	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 3-(4-hydroxy-benzoyl)-phenyl ester	DMH71N6	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 3-(4-methoxy-benzoyl)-phenyl ester	DMFVE3N	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 3-benzoyl-phenyl ester	DMLXHAI	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 4-(2-hydroxy-benzoyl)-phenyl ester	DMSYXHF	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 4-(2-methoxy-benzoyl)-phenyl ester	DM8LWM3	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 4-(3-methoxy-benzoyl)-phenyl ester	DMK97WC	Discovery agent	N.A.	Investigative	[9]
Sulfamic acid 4-benzoyl-phenyl ester	DMDUW9F	Discovery agent	N.A.	Investigative	[9]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Breast cancer	2C82	Breast tissue	1.80E-38	-0.79	-1.15
Prostate cancer	2C82	Prostate	4.91E-02	-0.28	-0.52
Endometriosis	GA10	Endometrium tissue	3.29E-02	0.29	0.67

References

• [1] Review of estrone sulfatase and its inhibitors--an important new target against hormone dependent breast cancer. Curr Med Chem. 2002 Jan;9(2):263-73.
• [2] Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. J Med Chem. 2010 Mar 11;53(5):2155-70.
• [3] Synergistic effects of E2MATE and norethindrone acetate on steroid sulfatase inhibition: a randomized phase I proof-of-principle clinical study in women of reproductive age. Reprod Sci. 2014 Oct;21(10):1256-65.
• [4] 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity. J Med Chem. 2006 Dec 28;49(26):7683-96.
• [5] Phase I study of STX 64 (667 Coumate) in breast cancer patients: the first study of a steroid sulfatase inhibitor. Clin Cancer Res. 2006 Mar 1;12(5):1585-92.
• [6] Thiosemicarbazones of formyl benzoic acids as novel potent inhibitors of estrone sulfatase. J Med Chem. 2007 Jul 26;50(15):3661-6.
• [7] Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase. Bioorg Med Chem Lett. 2004 Oct 4;14(19):4999-5002.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] 4,4'-Benzophenone-O,O'-disulfamate: a potent inhibitor of steroid sulfatase. Bioorg Med Chem Lett. 2002 Aug 19;12(16):2093-5.
• [10] Inhibition of estrone sulfatase (ES) by alkyl and cycloalkyl ester derivatives of 4-[(aminosulfonyl)oxy] benzoic acid. Bioorg Med Chem Lett. 2004 Feb 9;14(3):605-9.
• [11] Chiral aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole template: synthesis, absolute configuration, and in vitro activ... J Med Chem. 2008 Jul 24;51(14):4226-38.
• [12] Synthesis, in vitro and in vivo activity of benzophenone-based inhibitors of steroid sulfatase. Bioorg Med Chem. 2004 May 15;12(10):2759-72.
• [13] Nortropinyl-arylsulfonylureas as novel, reversible inhibitors of human steroid sulfatase. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3673-7.
• [14] Estrogenic potential of 2-alkyl-4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human steroid sulfatase. J Med Chem. 2003 Nov 6;46(23):5091-4.