Target Information
| Target General Information | Top | |||||
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| Target ID |
T70309
(Former ID: TTDR01182)
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| Target Name |
Steroid 5-alpha-reductase 1 (SRD5A1)
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| Synonyms |
SRD5A1; SR type 1; 5-alpha reductase 1
Click to Show/Hide
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| Gene Name |
SRD5A1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Prostate disease [ICD-11: GA91] | |||||
| Function |
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5- alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
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| BioChemical Class |
CH-CH donor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.3.1.22
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| Sequence |
MATATGVAEERLLAALAYLQCAVGCAVFARNRQTNSVYGRHALPSHRLRVPARAAWVVQE
LPSLALPLYQYASESAPRLRSAPNCILLAMFLVHYGHRCLIYPFLMRGGKPMPLLACTMA IMFCTCNGYLQSRYLSHCAVYADDWVTDPRFLIGFGLWLTGMLINIHSDHILRNLRKPGD TGYKIPRGGLFEYVTAANYFGEIMEWCGYALASWSVQGAAFAFFTFCFLSGRAKEHHEWY LRKFEEYPKFRKIIIPFLF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T01FJS | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | FR-146687 | Drug Info | Phase 2 | Prostate disease | [1] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | MK-386 | Drug Info | Discontinued in Phase 2 | Acne vulgaris | [2] | |
| 2 | AS-601811 | Drug Info | Discontinued in Phase 1 | Acne vulgaris | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 22 Inhibitor drugs | + | ||||
| 1 | FR-146687 | Drug Info | [1] | |||
| 2 | MK-386 | Drug Info | [4] | |||
| 3 | AS-601811 | Drug Info | [1], [5] | |||
| 4 | Bexlosteride | Drug Info | [4] | |||
| 5 | (3-fluoro-4-(4-phenoxybenzoyl)phenyl)acetic acid | Drug Info | [6] | |||
| 6 | (3-methyl-4-(4-phenoxybenzoyl)phenyl)acetic acid | Drug Info | [6] | |||
| 7 | (E)-3-(4-(4-phenoxybenzoyl)phenyl)acrylic acid | Drug Info | [6] | |||
| 8 | 1,2,5,6-tetrahydro pyrido[1,2-a]quinolin-3-one | Drug Info | [7] | |||
| 9 | 1-Methyl-5-(4-phenylazo-phenyl)-piperidin-2-one | Drug Info | [8] | |||
| 10 | 1-Methyl-5-phenyl-piperidin-2-one | Drug Info | [8] | |||
| 11 | 2,3,5,6-Tetrafluoro-4-pentafluorophenylazo-phenol | Drug Info | [9] | |||
| 12 | 3,4,5,6-Tetrahydrobenzo[c]quinolizin-3-(4aH)-one | Drug Info | [7] | |||
| 13 | 4,4'-dihydroxyoctafluoroazobenzene | Drug Info | [9] | |||
| 14 | 4-(4-phenoxybenzoyl)benzoic acid | Drug Info | [6] | |||
| 15 | 4-Methyl-5,6-dihydro-pyrido[1,2-a]quinolin-3-one | Drug Info | [7] | |||
| 16 | 4-[4-(benzhydryloxy)benzoyl]benzoic acid | Drug Info | [6] | |||
| 17 | 4-[4-benzyloxy)benzoyl]benzoic acid | Drug Info | [6] | |||
| 18 | 5-(4-Chloro-phenyl)-1-methyl-piperidin-2-one | Drug Info | [8] | |||
| 19 | 5-(4-Chloro-phenyl)-1-methyl-piperidine-2-thione | Drug Info | [8] | |||
| 20 | GP515 | Drug Info | [10] | |||
| 21 | LY-266111 | Drug Info | [8] | |||
| 22 | {4-[4-(4-bromophenoxy)benzoyl]phenyl}acetic acid | Drug Info | [6] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| 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 | 13 | Degree centrality | 1.40E-03 | Betweenness centrality | 2.98E-04 |
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| Closeness centrality | 1.49E-01 | Radiality | 1.19E+01 | Clustering coefficient | 3.72E-01 |
| Neighborhood connectivity | 9.08E+00 | Topological coefficient | 2.81E-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 Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 3 BioCyc Pathways | + | ||||
| 1 | Superpathway of steroid hormone biosynthesis | |||||
| 2 | Allopregnanolone biosynthesis | |||||
| 3 | Androgen biosynthesis | |||||
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Steroid hormone biosynthesis | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Androgen and Estrogen Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Androgen biosynthesis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5alpha-reductase inhibitor, in normal subjects treated with single or multiple doses. Br J Clin Pharmacol. 2002 Sep;54(3):283-94. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006173) | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013228) | |||||
| REF 4 | Synthesis of 8-chloro-benzo[c]quinolizin-3-ones as potent and selective inhibitors of human steroid 5alpha-reductase 1. Bioorg Med Chem Lett. 2000 Feb 21;10(4):353-6. | |||||
| 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 800013228) | |||||
| REF 6 | 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 7 | Benzo[c]quinolizin-3-ones: a novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1. J Med Chem. 2000 Oct 5;43(20):3718-35. | |||||
| REF 8 | Simple bi- and tricyclic inhibitors of human steroid 5alpha-reductase. Bioorg Med Chem Lett. 2000 Sep 4;10(17):1909-11. | |||||
| REF 9 | Hydroxyperfluoroazobenzenes: novel inhibitors of enzymes of androgen biosynthesis. J Med Chem. 1990 Sep;33(9):2452-5. | |||||
| REF 10 | 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. | |||||
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