Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T71390
(Former ID: TTDR01183)
|
|||||
| Target Name |
Steroid 5-alpha-reductase 2 (SRD5A2)
|
|||||
| Synonyms |
Type 2 steroid 5alpha-reductase (5alpha-R); SRD5A2; SR type 2; 5-alpha reductase 2; 5 alpha-SR2
Click to Show/Hide
|
|||||
| Gene Name |
SRD5A2
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Prostate hyperplasia [ICD-11: GA90] | |||||
| Function |
Converts testosterone (T) into 5-alpha- dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Click to Show/Hide
|
|||||
| BioChemical Class |
CH-CH donor oxidoreductase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 1.3.1.22
|
|||||
| Sequence |
MQVQCQQSPVLAGSATLVALGALALYVAKPSGYGKHTESLKPAATRLPARAAWFLQELPS
FAVPAGILARQPLSLFGPPGTVLLGLFCVHYFHRTFVYSLLNRGRPYPAILILRGTAFCT GNGVLQGYYLIYCAEYPDGWYTDIRFSLGVFLFILGMGINIHSDYILRQLRKPGEISYRI PQGGLFTYVSGANFLGEIIEWIGYALATWSLPALAFAFFSLCFLGLRAFHHHRFYLKMFE DYPKSRKALIPFIF Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T66JU3 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Finasteride | Drug Info | Approved | Benign prostatic hyperplasia | [2], [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 13 Inhibitor drugs | + | ||||
| 1 | Finasteride | Drug Info | [1] | |||
| 2 | (3-fluoro-4-(4-phenoxybenzoyl)phenyl)acetic acid | Drug Info | [4] | |||
| 3 | (3-methyl-4-(4-phenoxybenzoyl)phenyl)acetic acid | Drug Info | [4] | |||
| 4 | (E)-3-(4-(4-phenoxybenzoyl)phenyl)acrylic acid | Drug Info | [4] | |||
| 5 | 2,3,5,6-Tetrafluoro-4-pentafluorophenylazo-phenol | Drug Info | [5] | |||
| 6 | 3-[4-(4-phenoxybenzoyl)phenyl]propanoic acid | Drug Info | [4] | |||
| 7 | 4-(4-phenoxybenzoyl)phenylacetic acid | Drug Info | [4] | |||
| 8 | 4-[4-(benzhydryloxy)benzoyl]benzoic acid | Drug Info | [4] | |||
| 9 | 4-[4-(benzoylamino)benzoyl]benzoic acid | Drug Info | [4] | |||
| 10 | 4-[4-(benzylamino)benzoyl]benzoic acid | Drug Info | [4] | |||
| 11 | 4-[4-benzyloxy)benzoyl]benzoic acid | Drug Info | [4] | |||
| 12 | GP515 | Drug Info | [6] | |||
| 13 | {4-[4-(4-bromophenoxy)benzoyl]phenyl}acetic acid | Drug Info | [4] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: [[(2~{R},3~{S},4~{R},5~{R})-5-[4-[(1~{S},3~{a}~{S},3~{b}~{S},5~{a}~{R},8~{S},9~{a}~{R},9~{b}~{S},11~{a}~{S})-1-(~{tert}-butylcarbamoyl)-9~{a},11~{a}-dimethyl-7-oxidanylidene-1,2,3,3~{a},3~{b},4,5,5~{a},6,8,9,9~{b},10,11-tetradecahydroindeno[5,4-f]quinolin-8-yl]-3-aminocarbonyl-4~{H}-pyridin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{R},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3-oxidanyl-4-phosphonooxy-oxolan-2-yl]methyl hydrogen phosphate | Ligand Info | |||||
| Structure Description | Crystal structure of Steroid 5-alpha-reductase 2 in complex with Finasteride | PDB:7BW1 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [7] |
| PDB Sequence |
CQQSPVLAGS
14 ATLVALGALA24 LYVAKPSGYG34 KHTEATRLPA49 RAAWFLQELP59 SFAVPAGILA 69 RQPLSLFGPP79 GTVLLGLFCV89 HYFHRTFVYS99 LLNRGRPYPA109 ILILRGTAFC 119 TGNGVLQGYY129 LIYCAEYPDG139 WYTDIRFSLG149 VFLFILGMGI159 NIHSDYILRQ 169 LRKPGEISYR179 IPQGGLFTYV189 SGANFLGEII199 EWIGYALATW209 SLPALAFAFF 219 SLCFLGLRAF229 HHHRFYLKMF239 EDYPKSRKAL249 IPFIF
|
|||||
|
|
LEU20
4.076
LEU23
3.946
ALA24
3.663
VAL27
4.792
SER31
3.364
TYR33
2.934
GLY34
3.380
LYS35
2.853
TRP53
3.433
GLN56
3.813
GLU57
2.866
TYR91
4.479
ARG94
2.866
TYR98
3.074
ASN102
2.812
ARG103
3.959
GLY104
3.289
ARG105
3.079
TYR107
3.743
LEU111
3.862
ARG114
3.007
GLY115
3.849
PHE118
3.352
CYS119
4.690
ASN160
2.767
ASP164
2.730
LEU167
3.629
LEU170
3.738
ARG171
3.021
SER177
3.593
TYR178
2.804
ARG179
2.870
PRO181
4.176
ASN193
2.952
PHE194
3.472
GLU197
2.815
TRP201
3.195
PHE216
3.944
PHE219
3.687
SER220
3.126
PHE223
3.389
LEU224
3.795
ARG227
2.520
HIS231
2.768
TYR235
3.122
|
|||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
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
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Steroid hormone biosynthesis | hsa00140 | Affiliated Target |
|
| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 13 | Degree centrality | 1.40E-03 | Betweenness centrality | 1.53E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 1.48E-01 | Radiality | 1.19E+01 | Clustering coefficient | 3.97E-01 |
| Neighborhood connectivity | 9.38E+00 | Topological coefficient | 2.91E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "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 | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| BioCyc | [+] 3 BioCyc Pathways | + | ||||
| 1 | Superpathway of steroid hormone biosynthesis | |||||
| 2 | Allopregnanolone biosynthesis | |||||
| 3 | Androgen biosynthesis | |||||
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Steroid hormone biosynthesis | |||||
| 2 | Prostate cancer | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Androgen biosynthesis | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| 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: 6818). | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | Novel 5alpha-reductase inhibitors: synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids. J Med Chem. 2006 Jan 26;49(2):748-59. | |||||
| REF 5 | Hydroxyperfluoroazobenzenes: novel inhibitors of enzymes of androgen biosynthesis. J Med Chem. 1990 Sep;33(9):2452-5. | |||||
| REF 6 | 19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2. J Med Chem. 1997 Mar 28;40(7):1112-29. | |||||
| REF 7 | Structure of human steroid 5Alpha-reductase 2 with anti-androgen drug finasteride. Res Sq. 2020 Jul 15:rs.3.rs-40159. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.