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
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
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002526 acute inflammatory response IEA
GO:0002544 chronic inflammatory response IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0034097 response to cytokine IEA

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 18/06/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1377.