mPGES1

Target id: 1377

Nomenclature: mPGES1

Family: Prostaglandin synthases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     mPGES1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - PTGES prostaglandin E synthase
Mouse - - Ptges prostaglandin E synthase
Rat - - Ptges prostaglandin E synthase
Previous and Unofficial Names
MGST1-L1 | PIG12 | Prostaglandin E synthase | MGST-IV | MGST1-like 1 | microsomal prostaglandin E synthase-1 | Pges
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structures of mPGES-1 inhibitor complexes.
PDB Id:  4YK5
Ligand:  compound 30 [PMID: 15953724]
Resolution:  1.45Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 5.3.99.3 PGH2 = PGE2

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 44 [PMID: 19748780] Hs Inhibition 9.0 pIC50 1
pIC50 9.0 (IC50 1x10-9 M) [1]
compound 30 [PMID: 15953724] Hs Inhibition 8.5 pIC50 5
pIC50 8.5 (IC50 3x10-9 M) [5]
compound 39 [PMID: 23623673] Hs Inhibition 8.4 pIC50 6
pIC50 8.4 (IC50 4.1x10-9 M) [6]
compound III [PMID: 24045148] Hs Inhibition 6.7 – 7.1 pIC50 2,7
pIC50 7.1 (IC50 9x10-8 M) [2]
Description: Vs. recombinant human mPGES-1.
pIC50 6.7 (IC50 1.8x10-7 M) [7]
Description: Vs. recombinant human mPGES-1.
compound III [PMID: 24045148] Rn Inhibition 6.0 – 6.1 pIC50 2,7
pIC50 6.1 (IC50 9x10-7 M) [2]
Description: Vs. recombinant rat mPGES-1.
pIC50 6.0 (IC50 9.2x10-7 M) [7]
Description: Vs. recombinant rat mPGES-1.
View species-specific inhibitor tables
Immunopharmacology Comments
Inhibition of mPGES-1 is proposed as a potentially safer alternative to COX-2 inhibition for the treatment of pain and inflammation, with a reduced risk of cardiovascular side effects [4]. Inhibition of mPGES-1 in A549 cells and mouse macrophages by compound III [PMID: 24045148] reduces PGE2 production [2].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  acute inflammatory response (GO:0002526) IEA
chronic inflammatory response (GO:0002544) IEA
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  response to cytokine (GO:0034097) IEA
References: 

References

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1. Giroux A, Boulet L, Brideau C, Chau A, Claveau D, Côté B, Ethier D, Frenette R, Gagnon M, Guay J et al.. (2009) Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors. Bioorg. Med. Chem. Lett.19 (20): 5837-41. [PMID:19748780]

2. Leclerc P, Idborg H, Spahiu L, Larsson C, Nekhotiaeva N, Wannberg J, Stenberg P, Korotkova M, Jakobsson PJ. (2013) Characterization of a human and murine mPGES-1 inhibitor and comparison to mPGES-1 genetic deletion in mouse models of inflammation. Prostaglandins Other Lipid Mediat.107: 26-34. [PMID:24045148]

3. Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A et al.. (2015) Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J. Med. Chem.58 (11): 4727-37. [PMID:25961169]

4. Ozen G, Gomez I, Daci A, Deschildre C, Boubaya L, Teskin O, Uydeş-Doğan BS, Jakobsson PJ, Longrois D, Topal G et al.. (2017) Inhibition of microsomal PGE synthase-1 reduces human vascular tone by increasing PGI2 : a safer alternative to COX-2 inhibition. Br. J. Pharmacol.174 (22): 4087-4098. [PMID:28675448]

5. Riendeau D, Aspiotis R, Ethier D, Gareau Y, Grimm EL, Guay J, Guiral S, Juteau H, Mancini JA, Méthot N et al.. (2005) Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886. Bioorg. Med. Chem. Lett.15 (14): 3352-5. [PMID:15953724]

6. Shiro T, Kakiguchi K, Takahashi H, Nagata H, Tobe M. (2013) 7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors. Bioorg. Med. Chem.21 (11): 2868-78. [PMID:23623673]

7. Wannberg J, Alterman M, Malm J, Stenberg P, Westman J, Wallberg H. (2011) Microsomal prostaglandin e synthase-1 (mpges1) inhibitors. Patent number: WO2011023812. Assignee: Novasaid Ab. Priority date: 27/08/2009. Publication date: 03/03/2011.

How to cite this page

Prostaglandin synthases: mPGES1. Last modified on 23/11/2017. Accessed on 12/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1377.