Target Information
| Target General Information | Top | |||||
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| Target ID |
T02562
(Former ID: TTDR00630)
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| Target Name |
Prostaglandin E synthase (PTGES)
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| Synonyms |
p53-induced gene 12 protein; PIG12; PGES; PGE synthase; P53-induced apoptosis protein 12; Microsomal prostaglandin E synthase 1; Microsomal glutathione S-transferase 1-like 1; MPGES1; MPGES-1; MGST1L1; MGST1-L1
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| Gene Name |
PTGES
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| Function |
Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).
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| BioChemical Class |
Intramolecular oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 5.3.99.3
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| Sequence |
MPAHSLVMSSPALPAFLLCSTLLVIKMYVVAIITGQVRLRKKAFANPEDALRHGGPQYCR
SDPDVERCLRAHRNDMETIYPFLFLGFVYSFLGPNPFVAWMHFLVFLVGRVAHTVAYLGK LRAPIRSVTYTLAQLPCASMALQILWEAARHL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T47HTN | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | AAD-2004 | Drug Info | Phase 1 | Alzheimer disease | [1] | |
| Patented Agent(s) | [+] 3 Patented Agents | + | ||||
| 1 | Carboxylic acid derivative 1 | Drug Info | Patented | Neoplasm | [2], [3] | |
| 2 | Imidazole benzamide derivative 1 | Drug Info | Patented | Knee pain | [3] | |
| 3 | Methyl-piperidine compound 1 | Drug Info | Patented | Neoplasm | [2], [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 33 Inhibitor drugs | + | ||||
| 1 | AAD-2004 | Drug Info | [1] | |||
| 2 | Alpha-substituted pirinixic acid and pirinixic acid ester derivative 1 | Drug Info | [3] | |||
| 3 | Benzamide derivative 14 | Drug Info | [3] | |||
| 4 | Benzamide derivative 15 | Drug Info | [3] | |||
| 5 | Benzamide derivative 16 | Drug Info | [3] | |||
| 6 | Benzamide derivative 18 | Drug Info | [3] | |||
| 7 | Benzimidazole derivative 11 | Drug Info | [3] | |||
| 8 | Benzimidazole derivative 12 | Drug Info | [3] | |||
| 9 | Benzimidazole derivative 13 | Drug Info | [3] | |||
| 10 | Benzimidazole derivative 14 | Drug Info | [3] | |||
| 11 | Benzimidazole derivative 15 | Drug Info | [3] | |||
| 12 | Benzimidazole derivative 16 | Drug Info | [3] | |||
| 13 | Benzimidazole derivative 17 | Drug Info | [3] | |||
| 14 | Betais-sulfonylamino derivative 1 | Drug Info | [3] | |||
| 15 | Boswellia acid derivative 1 | Drug Info | [3] | |||
| 16 | Carboxylic acid derivative 1 | Drug Info | [3] | |||
| 17 | Imidazole benzamide derivative 1 | Drug Info | [3] | |||
| 18 | Imidazopyridine derivative 5 | Drug Info | [3] | |||
| 19 | Imidazopyridine derivative 6 | Drug Info | [3] | |||
| 20 | Imidazopyridine derivative 7 | Drug Info | [3] | |||
| 21 | Methyl-piperidine compound 1 | Drug Info | [3] | |||
| 22 | Phthalazinone derivative 1 | Drug Info | [3] | |||
| 23 | Piperidine carboxamide derivative 1 | Drug Info | [3] | |||
| 24 | PMID28627961-Compound-22 | Drug Info | [3] | |||
| 25 | PMID28627961-Compound-30 | Drug Info | [3] | |||
| 26 | PMID28627961-Compound-31 | Drug Info | [3] | |||
| 27 | PMID28627961-Compound-32 | Drug Info | [3] | |||
| 28 | PMID28627961-Compound-33 | Drug Info | [3] | |||
| 29 | PMID28627961-Compound-41 | Drug Info | [3] | |||
| 30 | PMID28627961-Compound-44 | Drug Info | [3] | |||
| 31 | Polycyclic compound 1 | Drug Info | [3] | |||
| 32 | Pyrimidine derivative 2 | Drug Info | [3] | |||
| 33 | L-655240 | Drug Info | [4] | |||
| 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: Glutathione | Ligand Info | |||||
| Structure Description | Crystal structure of Human PS-1 | PDB:4AL0 | ||||
| Method | X-ray diffraction | Resolution | 1.16 Å | Mutation | No | [5] |
| PDB Sequence |
VMSSPALPAF
16 LLCSTLLVIK26 MYVVAIITGQ36 VRLRKKAFAN46 PEDALRHGGP56 QYCRSDPDVE 66 RCLRAHRNDM76 ETIYPFLFLG86 FVYSFLGPNP96 FVAWMHFLVF106 LVGRVAHTVA 116 YLGKLRAPIR126 SVTYTLAQLP136 CASMALQILW146 EAARHL
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: B-Octylglucoside | Ligand Info | |||||
| Structure Description | Crystal structure of Human PS-1 | PDB:4AL0 | ||||
| Method | X-ray diffraction | Resolution | 1.16 Å | Mutation | No | [5] |
| PDB Sequence |
VMSSPALPAF
16 LLCSTLLVIK26 MYVVAIITGQ36 VRLRKKAFAN46 PEDALRHGGP56 QYCRSDPDVE 66 RCLRAHRNDM76 ETIYPFLFLG86 FVYSFLGPNP96 FVAWMHFLVF106 LVGRVAHTVA 116 YLGKLRAPIR126 SVTYTLAQLP136 CASMALQILW146 EAARHL
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
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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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Arachidonic acid metabolism | hsa00590 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 1.03E-04 |
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| Closeness centrality | 1.99E-01 | Radiality | 1.34E+01 | Clustering coefficient | 6.67E-01 |
| Neighborhood connectivity | 9.67E+00 | Topological coefficient | 2.84E-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 | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | C20 prostanoid biosynthesis | |||||
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Arachidonic acid metabolism | |||||
| 2 | Metabolic pathways | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | IL1 Signaling Pathway | |||||
| 2 | TCR Signaling Pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Arachidonic Acid Metabolism | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Arachidonic acid metabolism | |||||
| 2 | Eicosanoid Synthesis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Concurrent blockade of free radical and microsomal prostaglandin E synthase-1-mediated PGE2 production improves safety and efficacy in a mouse model of amyotrophic lateral sclerosis. J Neurochem. 2012 Sep;122(5):952-61. | |||||
| REF 2 | VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016).Expert Opin Ther Pat. 2017 Sep;27(9):987-1004. | |||||
| REF 3 | Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Sep;27(9):1047-1059. | |||||
| REF 4 | Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886. Bioorg Med Chem Lett. 2005 Jul 15;15(14):3352-5. | |||||
| REF 5 | Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3806-11. | |||||
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