Target Information
| Target General Information | Top | |||||
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| Target ID |
T44011
(Former ID: TTDR00587)
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| Target Name |
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)
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| Synonyms |
Short chain dehydrogenase/reductase family 28C member 1; SDR28C1; Placental 17-beta-hydroxysteroid dehydrogenase; Estradiol 17-beta-dehydrogenase 1; EDHB17; EDH17B2; EDH17B1; E2DH; E17KSR; 20-alpha-HSD; 20 alpha-hydroxysteroid dehydrogenase; 17-beta-Hydroxysteroid dehydrogenase type 1; 17-beta-HSD 1
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| Gene Name |
HSD17B1
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| Target Type |
Clinical trial target
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| Function |
Has 20-alpha-HSD activity. Uses preferentially NADH. Favors the reduction of estrogens and androgens.
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| BioChemical Class |
CH-OH donor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.1.1.62
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| Sequence |
MARTVVLITGCSSGIGLHLAVRLASDPSQSFKVYATLRDLKTQGRLWEAARALACPPGSL
ETLQLDVRDSKSVAAARERVTEGRVDVLVCNAGLGLLGPLEALGEDAVASVLDVNVVGTV RMLQAFLPDMKRRGSGRVLVTGSVGGLMGLPFNDVYCASKFALEGLCESLAVLLLPFGVH LSLIECGPVHTAFMEKVLGSPEEVLDRTDIHTFHRFYQYLAHSKQVFREAAQNPEEVAEV FLTALRAPKPTLRYFTTERFLPLLRMRLDDPSGSNYVTAMHREVFGDVPAKAEAGAEAGG GAGPGAEDEAGRGAVGDPELGDPPAAPQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Estrone | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF HUMAN 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 COMPLEXED WITH ESTRONE AND NADP+ | PDB:6MNE | ||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | No | [11] |
| PDB Sequence |
ARTVVLITGC
10 SSGIGLHLAV20 RLASDPSQSF30 KVYATLRDLK40 TQGRLWEAAR50 ALACPPGSLE 60 TLQLDVRDSK70 SVAAARERVT80 EGRVDVLVCN90 AGLGLLGPLE100 ALGEDAVASV 110 LDVNVVGTVR120 MLQAFLPDMK130 RRGSGRVLVT140 GSVGGLMGLP150 FNDVYCASKF 160 ALEGLCESLA170 VLLLPFGVHL180 SLIECGPVHT190 GSPEEVLDRT207 DIHTFHRFYQ 217 YLAHSKQVFR227 EAAQNPEEVA237 EVFLTALRAP247 KPTLRYFTTE257 RFLPLLRMRL 267 DDPSGSNYVT277 AMHREVFG
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| Ligand Name: Testosterone | Ligand Info | |||||
| Structure Description | Crystal structure of 17beta-Hydroxysteroid Dehydrogenase Type 1 complexed with Testosterone | PDB:1JTV | ||||
| Method | X-ray diffraction | Resolution | 1.54 Å | Mutation | No | [12] |
| PDB Sequence |
ARTVVLITGC
10 SSGIGLHLAV20 RLASDPSQSF30 KVYATLRDLK40 TQGRLWEAAR50 ALACPPGSLE 60 TLQLDVRDSK70 SVAAARERVT80 EGRVDVLVCN90 AGLGLLGPLE100 ALGEDAVASV 110 LDVNVVGTVR120 MLQAFLPDMK130 RRGSGRVLVT140 GSVGGLMGLP150 FNDVYCASKF 160 ALEGLCESLA170 VLLLPFGVHL180 SLIECGPVHT190 GSPEEVLDRT207 DIHTFHRFYQ 217 YLAHSKQVFR227 EAAQNPEEVA237 EVFLTALRAP247 KPTLRYFTTE257 RFLPLLRMRL 267 DDPSGSNYVT277 AMHREVFG
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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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| 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 | ||
| Ovarian steroidogenesis | hsa04913 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 5.86E-04 |
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| Closeness centrality | 1.76E-01 | Radiality | 1.29E+01 | Clustering coefficient | 2.38E-01 |
| Neighborhood connectivity | 7.43E+00 | Topological coefficient | 2.23E-01 | Eccentricity | 11 |
| 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 | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 2 BioCyc Pathways | + | ||||
| 1 | Superpathway of steroid hormone biosynthesis | |||||
| 2 | Estradiol biosynthesis I | |||||
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Steroid hormone biosynthesis | |||||
| 2 | Metabolic pathways | |||||
| 3 | Ovarian steroidogenesis | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | FSH Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Androgen/estrogene/progesterone biosynthesis | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Androgen and Estrogen Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | The canonical retinoid cycle in rods (twilight vision) | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Steroid Biosynthesis | |||||
| 2 | Metabolism of steroid hormones and vitamin D | |||||
| 3 | Prostate Cancer | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99. | |||||
| REF 2 | New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxyst... J Med Chem. 2009 Nov 12;52(21):6724-43. | |||||
| REF 3 | Substituted 6-phenyl-2-naphthols. Potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1): design,... J Med Chem. 2008 Aug 14;51(15):4685-98. | |||||
| REF 4 | Modification of estrone at the 6, 16, and 17 positions: novel potent inhibitors of 17beta-hydroxysteroid dehydrogenase type 1. J Med Chem. 2006 Feb 23;49(4):1325-45. | |||||
| REF 5 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 6 | Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors... J Med Chem. 2008 Apr 10;51(7):2158-69. | |||||
| REF 7 | Novel estrone mimetics with high 17beta-HSD1 inhibitory activity. Bioorg Med Chem. 2010 May 15;18(10):3494-505. | |||||
| REF 8 | Design, synthesis, biological evaluation and pharmacokinetics of bis(hydroxyphenyl) substituted azoles, thiophenes, benzenes, and aza-benzenes as p... J Med Chem. 2008 Nov 13;51(21):6725-39. | |||||
| REF 9 | Design, synthesis and biological evaluation of bis(hydroxyphenyl) azoles as potent and selective non-steroidal inhibitors of 17beta-hydroxysteroid ... Bioorg Med Chem. 2008 Jun 15;16(12):6423-35. | |||||
| REF 10 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 11 | Crystal structures of human 17beta-hydroxysteroid dehydrogenase type 1 complexed with estrone and NADP(+) reveal the mechanism of substrate inhibition. FEBS J. 2019 Jun;286(11):2155-2166. | |||||
| REF 12 | Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase. FASEB J. 2003 Feb;17(2):274-6. | |||||
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