Target Information
| Target General Information | Top | |||||
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| Target ID |
T33489
(Former ID: TTDC00149)
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| Target Name |
Steryl-sulfatase (STS)
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| Synonyms |
Steryl-sulfate sulfohydrolase; Steroid sulfatase; STS; Estrone sulfatase; Arylsulfatase C; ASC
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| Gene Name |
STS
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Allergic/hypersensitivity disorder [ICD-11: 4A80-4A8Z] | |||||
| Function |
Conversion of sulfated steroid precursors to estrogens during pregnancy.
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| BioChemical Class |
Sulfuric ester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.6.2
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| Sequence |
MPLRKMKIPFLLLFFLWEAESHAASRPNIILVMADDLGIGDPGCYGNKTIRTPNIDRLAS
GGVKLTQHLAASPLCTPSRAAFMTGRYPVRSGMASWSRTGVFLFTASSGGLPTDEITFAK LLKDQGYSTALIGKWHLGMSCHSKTDFCHHPLHHGFNYFYGISLTNLRDCKPGEGSVFTT GFKRLVFLPLQIVGVTLLTLAALNCLGLLHVPLGVFFSLLFLAALILTLFLGFLHYFRPL NCFMMRNYEIIQQPMSYDNLTQRLTVEAAQFIQRNTETPFLLVLSYLHVHTALFSSKDFA GKSQHGVYGDAVEEMDWSVGQILNLLDELRLANDTLIYFTSDQGAHVEEVSSKGEIHGGS NGIYKGGKANNWEGGIRVPGILRWPRVIQAGQKIDEPTSNMDIFPTVAKLAGAPLPEDRI IDGRDLMPLLEGKSQRSDHEFLFHYCNAYLNAVRWHPQNSTSIWKAFFFTPNFNPVGSNG CFATHVCFCFGSYVTHHDPPLLFDISKDPRERNPLTPASEPRFYEILKVMQEAADRHTQT LPEVPDQFSWNNFLWKPWLQLCCPSTGLSCQCDREKQDKRLSR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Tranilast | Drug Info | Approved | Ocular allergy | [2], [3] | |
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | Coumate | Drug Info | Phase 2 | Breast cancer | [4] | |
| 2 | PGL-2 | Drug Info | Phase 2 | Endometriosis | [5] | |
| 3 | PGL-2001 | Drug Info | Phase 2 | Endometriosis | [6] | |
| 4 | STX-140 | Drug Info | Phase 2 | Osteoporosis | [7] | |
| 5 | STX 64 | Drug Info | Phase 1 | Prostate cancer | [8] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 46 Inhibitor drugs | + | ||||
| 1 | Tranilast | Drug Info | [1] | |||
| 2 | Coumate | Drug Info | [9] | |||
| 3 | PGL-2 | Drug Info | [10] | |||
| 4 | PGL-2001 | Drug Info | [10] | |||
| 5 | STX-140 | Drug Info | [11] | |||
| 6 | STX 64 | Drug Info | [12] | |||
| 7 | 2',4'-dicyanobiphenyl-4-yl sulfamate | Drug Info | [9] | |||
| 8 | 2-(4-cyclohexylthiosemicarbazono)methyl-phenol | Drug Info | [13] | |||
| 9 | 2-Adamantan-2-ylidenemethyl-benzooxazol-6-ol | Drug Info | [14] | |||
| 10 | 2-Amino-3-Oxo-4-Sulfo-Butyric Acid | Drug Info | [15] | |||
| 11 | 2-ethylestradiol 3,17-O,O-bis-sulfamate | Drug Info | [11] | |||
| 12 | 2-methylsulfanylestradiol 3,17-O,O-bis-sulfamate | Drug Info | [11] | |||
| 13 | 3-(4-cyclohexylthiosemicarbazono)methyl-phenol | Drug Info | [13] | |||
| 14 | 3-(4-hexylthiosemicarbazono)methyl-benzoic acid | Drug Info | [13] | |||
| 15 | 3-{3-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate | Drug Info | [16] | |||
| 16 | 3-{4-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate | Drug Info | [16] | |||
| 17 | 4-(4-cyclohexylthiosemicarbazono)methyl-phenol | Drug Info | [13] | |||
| 18 | 4-Sulfamoyloxy-benzoic acid butyl ester | Drug Info | [17] | |||
| 19 | 4-Sulfamoyloxy-benzoic acid cycloheptyl ester | Drug Info | [17] | |||
| 20 | 4-Sulfamoyloxy-benzoic acid cyclohexyl ester | Drug Info | [17] | |||
| 21 | 4-Sulfamoyloxy-benzoic acid cyclooctyl ester | Drug Info | [17] | |||
| 22 | 4-Sulfamoyloxy-benzoic acid cyclopentyl ester | Drug Info | [17] | |||
| 23 | 4-Sulfamoyloxy-benzoic acid heptyl ester | Drug Info | [17] | |||
| 24 | 4-Sulfamoyloxy-benzoic acid hexyl ester | Drug Info | [17] | |||
| 25 | 4-Sulfamoyloxy-benzoic acid nonyl ester | Drug Info | [17] | |||
| 26 | 4-Sulfamoyloxy-benzoic acid octyl ester | Drug Info | [17] | |||
| 27 | 4-Sulfamoyloxy-benzoic acid pentyl ester | Drug Info | [17] | |||
| 28 | 4-Sulfamoyloxy-benzoic acid propyl ester | Drug Info | [17] | |||
| 29 | 4-{4-[(aminosulfonyl)oxy]benzoyl}phenyl sulfamate | Drug Info | [18] | |||
| 30 | B-Octylglucoside | Drug Info | [15] | |||
| 31 | Benzomate | Drug Info | [19] | |||
| 32 | EMATE | Drug Info | [13] | |||
| 33 | Estradiol 17-O-sulfamate | Drug Info | [11] | |||
| 34 | Estradiol 3,17-O,O-bis-sulfamate | Drug Info | [11] | |||
| 35 | MHL cyclohexylthiosemicarbazone | Drug Info | [13] | |||
| 36 | Nortropinyl-arylsulfonylurea 3 | Drug Info | [20] | |||
| 37 | Sulfamic acid 2-nonyl-4-oxo-4H-chromen-6-yl ester | Drug Info | [21] | |||
| 38 | Sulfamic acid 3-(3-hydroxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 39 | Sulfamic acid 3-(3-methoxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 40 | Sulfamic acid 3-(4-hydroxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 41 | Sulfamic acid 3-(4-methoxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 42 | Sulfamic acid 3-benzoyl-phenyl ester | Drug Info | [16] | |||
| 43 | Sulfamic acid 4-(2-hydroxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 44 | Sulfamic acid 4-(2-methoxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 45 | Sulfamic acid 4-(3-methoxy-benzoyl)-phenyl ester | Drug Info | [16] | |||
| 46 | Sulfamic acid 4-benzoyl-phenyl ester | Drug Info | [16] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: B-Octylglucoside | Ligand Info | |||||
| Structure Description | Structure of Human Placental Estrone/DHEA Sulfatase | PDB:1P49 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [22] |
| PDB Sequence |
AASRPNIILV
32 MADDLGIGDP42 GCYGNKTIRT52 PNIDRLASGG62 VKLTQHLAAS72 PLTPSRAAFM 83 TGRYPVRSGM93 ASWSRTGVFL103 FTASSGGLPT113 DEITFAKLLK123 DQGYSTALIG 133 KWHLGMSCHS143 KTDFCHHPLH153 HGFNYFYGIS163 LTNLRDCKPG173 EGSVFTTGFK 183 RLVFLPLQIV193 GVTLLTLAAL203 NCLGLLHVPL213 GVFFSLLFLA223 ALILTLFLGF 233 LHYFRPLNCF243 MMRNYEIIQQ253 PMSYDNLTQR263 LTVEAAQFIQ273 RNTETPFLLV 283 LSYLHVHTAL293 FSSKDFAGKS303 QHGVYGDAVE313 EMDWSVGQIL323 NLLDELRLAN 333 DTLIYFTSDQ343 GAHVEEVSSK353 GEIHGGSNGI363 YKGGKANNWE373 GGIRVPGILR 383 WPRVIQAGQK393 IDEPTSNMDI403 FPTVAKLAGA413 PLPEDRIIDG423 RDLMPLLEGK 433 SQRSDHEFLF443 HYCNAYLNAV453 RWHPQNSTSI463 WKAFFFTPNF473 NPVCFATHVC 487 FCFGSYVTHH497 DPPLLFDISK507 DPRERNPLTP517 ASEPRFYEIL527 KVMQEAADRH 537 TQTLPEVPDQ547 FSWNNFLWKP557 WLQLCCPSTG567 LSCQCDRE
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| Ligand Name: (3S)-3-(sulfooxy)-L-serine | Ligand Info | |||||
| Structure Description | Structure of Human Placental Estrone/DHEA Sulfatase | PDB:1P49 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [22] |
| PDB Sequence |
AASRPNIILV
32 MADDLGIGDP42 GCYGNKTIRT52 PNIDRLASGG62 VKLTQHLAAS72 PLTPSRAAFM 83 TGRYPVRSGM93 ASWSRTGVFL103 FTASSGGLPT113 DEITFAKLLK123 DQGYSTALIG 133 KWHLGMSCHS143 KTDFCHHPLH153 HGFNYFYGIS163 LTNLRDCKPG173 EGSVFTTGFK 183 RLVFLPLQIV193 GVTLLTLAAL203 NCLGLLHVPL213 GVFFSLLFLA223 ALILTLFLGF 233 LHYFRPLNCF243 MMRNYEIIQQ253 PMSYDNLTQR263 LTVEAAQFIQ273 RNTETPFLLV 283 LSYLHVHTAL293 FSSKDFAGKS303 QHGVYGDAVE313 EMDWSVGQIL323 NLLDELRLAN 333 DTLIYFTSDQ343 GAHVEEVSSK353 GEIHGGSNGI363 YKGGKANNWE373 GGIRVPGILR 383 WPRVIQAGQK393 IDEPTSNMDI403 FPTVAKLAGA413 PLPEDRIIDG423 RDLMPLLEGK 433 SQRSDHEFLF443 HYCNAYLNAV453 RWHPQNSTSI463 WKAFFFTPNF473 NPVCFATHVC 487 FCFGSYVTHH497 DPPLLFDISK507 DPRERNPLTP517 ASEPRFYEIL527 KVMQEAADRH 537 TQTLPEVPDQ547 FSWNNFLWKP557 WLQLCCPSTG567 LSCQCDRE
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Steroid hormone biosynthesis | hsa00140 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 2.62E-03 |
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| Closeness centrality | 1.44E-01 | Radiality | 1.18E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.27E+01 | Topological coefficient | 4.49E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Steroid hormone biosynthesis | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Androgen and Estrogen Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Glycosphingolipid metabolism | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Estrogen metabolism | |||||
| 2 | Vitamin D Receptor Pathway | |||||
| 3 | Sphingolipid metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6326). | |||||
| REF 3 | Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20. | |||||
| REF 4 | Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer. Expert Rev Anticancer Ther. 2011 Feb;11(2):179-83. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026648) | |||||
| REF 6 | ClinicalTrials.gov (NCT01631981) PGL2001 Proof of Concept Study in Symptomatic Endometriosis. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT00592579) A Phase 2 Study With Panzem in Patients With Relapsed or Plateau Phase Multiple Myeloma. U.S. National Institutes of Health. | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020388) | |||||
| REF 9 | 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. | |||||
| REF 10 | 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. | |||||
| REF 11 | 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. | |||||
| REF 12 | 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. | |||||
| REF 13 | Thiosemicarbazones of formyl benzoic acids as novel potent inhibitors of estrone sulfatase. J Med Chem. 2007 Jul 26;50(15):3661-6. | |||||
| REF 14 | Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase. Bioorg Med Chem Lett. 2004 Oct 4;14(19):4999-5002. | |||||
| REF 15 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 16 | 4,4'-Benzophenone-O,O'-disulfamate: a potent inhibitor of steroid sulfatase. Bioorg Med Chem Lett. 2002 Aug 19;12(16):2093-5. | |||||
| REF 17 | 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. | |||||
| REF 18 | 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. | |||||
| REF 19 | Synthesis, in vitro and in vivo activity of benzophenone-based inhibitors of steroid sulfatase. Bioorg Med Chem. 2004 May 15;12(10):2759-72. | |||||
| REF 20 | Nortropinyl-arylsulfonylureas as novel, reversible inhibitors of human steroid sulfatase. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3673-7. | |||||
| REF 21 | 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. | |||||
| REF 22 | Structure of human estrone sulfatase suggests functional roles of membrane association. J Biol Chem. 2003 Jun 20;278(25):22989-97. | |||||
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