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mPGES1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1377

Nomenclature: mPGES1

Family: Prostaglandin synthases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 152 9q34.11 PTGES prostaglandin E synthase
Mouse 4 153 2 21.75 cM Ptges prostaglandin E synthase
Rat - - Ptges prostaglandin E synthase
Previous and Unofficial Names Click here for help
MGST1-L1 | PIG12 | Prostaglandin E synthase | MGST-IV | MGST1-like 1 | microsomal prostaglandin E synthase-1 | Pges
Database Links Click here for help
Alphafold O14684 (Hs), Q9JM51 (Mm)
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)
Pharos O14684 (Hs)
SynPHARM 82842 (in complex with compound 30 [PMID: 15953724])
UniProtKB O14684 (Hs), Q9JM51 (Mm)
Wikipedia PTGES (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Discovery of a Potent and Selective mPGES-1 Inhibitor for the Treatment of Pain; LY3023703 bound to human mPGES-1
PDB Id:  5BQI
Ligand:  LY3023703
Resolution:  1.88Å
Species:  Human
References:  8
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:  4
Enzyme Reaction Click here for help
EC Number: 5.3.99.3 PGH2 = PGE2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LY3023703 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 1
⤷ pIC50 9.0 (IC50 9.4x10-10 M) [1]
Description: Potency for inhibition of human mPGES-1 expressed in 293E cell microsomes
compound 44 [PMID: 19748780] Small molecule or natural product Primary target of this compound Hs Inhibition 9.0 pIC50 2
⤷ pIC50 9.0 (IC50 1x10-9 M) [2]
vipoglanstat Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 6
⤷ pIC50 8.7 (IC50 2x10-9 M) [6]
compound 30 [PMID: 15953724] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 7
⤷ pIC50 8.5 (IC50 3x10-9 M) [7]
compound 39 [PMID: 23623673] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 4.1x10-9 M) [9]
zaloglanstat Small molecule or natural product Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 10
⤷ pIC50 >7.3 (IC50 <5x10-8 M) [10]
Description: The IC50 is a binned value from patent WO2019058295A1
compound III [PMID: 24045148] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.7 – 7.1 pIC50 3,11
⤷ pIC50 7.1 (IC50 9x10-8 M) [3]
Description: Vs. recombinant human mPGES-1.
pIC50 6.7 (IC50 1.8x10-7 M) [11]
Description: Vs. recombinant human mPGES-1.
compound III [PMID: 24045148] Small molecule or natural product Immunopharmacology Ligand Rn Inhibition 6.0 – 6.1 pIC50 3,11
⤷ pIC50 6.1 (IC50 9x10-7 M) [3]
Description: Vs. recombinant rat mPGES-1.
pIC50 6.0 (IC50 9.2x10-7 M) [11]
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 [5]. Inhibition of mPGES-1 in A549 cells and mouse macrophages by compound III [PMID: 24045148] reduces PGE2 production [3].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes, IEA only
GO:0031620 regulation of fever generation ISS
GO:0050727 regulation of inflammatory response ISS
Immuno Process:  Cytokine production & signalling

References

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1. Banerjee A, Pawar MY, Patil S, Yadav PS, Kadam PA, Kattige VG, Deshpande DS, Pednekar PV, Pisat MK, Gharat LA. (2014) Development of 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as microsomal prostaglandin E(2) synthase-1 inhibitors. Bioorg Med Chem Lett, 24 (20): 4838-44. [PMID:25260492]

2. 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]

3. 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]

4. 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]

5. 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]

6. Priepke H, Doods H, Kuelzer R, Pfau R, Stenkamp D, Pelcman B, Roenn R. (2012) New compounds. Patent number: WO2012022793A1. Assignee: Boehringer Ingelheim International Gmbh. Priority date: 20/08/2010. Publication date: 23/02/2012.

7. 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]

8. Schiffler MA, Antonysamy S, Bhattachar SN, Campanale KM, Chandrasekhar S, Condon B, Desai PV, Fisher MJ, Groshong C, Harvey A et al.. (2016) Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin E Synthase-1 Inhibitors. J Med Chem, 59 (1): 194-205. [PMID:26653180]

9. 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]

10. Tandon M, Sant S, Khairatkar-Joshi N, Gudi G, Menon VCA, Talluri R. (2019) Mpges-1 inhibitor for the treatment of osteoarthritis pain. Patent number: WO2013186692A1. Assignee: Glenmark Pharmaceuticals. Priority date: 20/09/2017. Publication date: 28/02/2019.

11. 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.

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