mPGES1 | Prostaglandin synthases | IUPHAR Guide to IMMUNOPHARMACOLOGY

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mPGES1

  Target has curated data in GtoImmuPdb

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

Contents:

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 5.3.99.3
CATH/Gene3D 1.20.120.550
ChEMBL Target CHEMBL5658 (Hs), CHEMBL2046261 (Mm)
Ensembl Gene ENSG00000148344 (Hs), ENSMUSG00000050737 (Mm), ENSRNOG00000006320 (Rn)
Entrez Gene 9536 (Hs), 64292 (Mm), 59103 (Rn)
Human Protein Atlas ENSG00000148344 (Hs)
KEGG Enzyme 5.3.99.3
KEGG Gene hsa:9536 (Hs), mmu:64292 (Mm), rno:59103 (Rn)
OMIM 605172 (Hs)
SynPHARM 82842 (in complex with compound 30 [PMID: 15953724])
UniProtKB O14684 (Hs), Q9JM51 (Mm)
Wikipedia PTGES (Hs)
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 Value Parameter 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.

Contributors

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How to cite this page

Angelo A. Izzo.
Prostaglandin synthases: mPGES1. Last modified on 23/11/2017. Accessed on 17/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1377.