Top ▲

mPGES1

Click here for help

Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1377

Nomenclature: mPGES1

Family: Prostaglandin synthases

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
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
SynPHARM
UniProtKB
Wikipedia
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:  10
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:  5
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 3
pIC50 9.0 (IC50 1x10-9 M) [3]
vipoglanstat Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 8
pIC50 8.7 (IC50 2x10-9 M) [8]
AGU654 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 2
pIC50 8.5 (IC50 2.9x10-9 M) [2]
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 9
pIC50 8.5 (IC50 3x10-9 M) [9]
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 12
pIC50 8.4 (IC50 4.1x10-9 M) [12]
friluglanstat Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.9 – 8.2 pIC50 6
pIC50 8.2 (IC50 6.6x10-9 M) [6]
Description: Inhibition of mPGES1 in microsomes isolated from CHO-K1 cells transiently expressing human mPGES1
pIC50 7.9 (IC50 1.29x10-8 M) [6]
Description: Inhibition of PGE2 production in A549 epithelial cells
zaloglanstat Small molecule or natural product Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 13
pIC50 >7.3 (IC50 <5x10-8 M) [13]
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 4,14
pIC50 7.1 (IC50 9x10-8 M) [4]
Description: Vs. recombinant human mPGES-1.
pIC50 6.7 (IC50 1.8x10-7 M) [14]
Description: Vs. recombinant human mPGES-1.
crisdesalazine Small molecule or natural product Hs Inhibition 6.6 pIC50 11
pIC50 6.6 (IC50 2.49x10-7 M) [11]
Description: Inhibition of recombinant human mPGES-1 enzymatic activity.
compound III [PMID: 24045148] Small molecule or natural product Immunopharmacology Ligand Rn Inhibition 6.0 – 6.1 pIC50 4,14
pIC50 6.1 (IC50 9x10-7 M) [4]
Description: Vs. recombinant rat mPGES-1.
pIC50 6.0 (IC50 9.2x10-7 M) [14]
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 [7]. Inhibition of mPGES-1 in A549 cells and mouse macrophages by compound III [PMID: 24045148] reduces PGE2 production [4].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling

References

Show »

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. Ergül AG, Jordan PM, Dahlke P, Bal NB, Olğaç A, Uludağ O, Werz O, Çalışkan B, Banoglu E. (2024) Novel Benzimidazole Derivatives as Potent Inhibitors of Microsomal Prostaglandin E2 Synthase 1 for the Potential Treatment of Inflammation, Pain, and Fever. J Med Chem, [Epub ahead of print]. [PMID:39622054]

3. 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]

4. 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]

5. 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]

6. Otsu H. (2015) Heterocyclic derivative and pharmaceutical drug. Patent number: US9216968B2. Assignee: Nippon Shinyaku Co Ltd. Priority date: 17/08/2012. Publication date: 22/12/2015.

7. 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]

8. 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.

9. 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]

10. 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]

11. Shin JH, Lee YA, Lee JK, Lee YB, Cho W, Im DS, Lee JH, Yun BS, Springer JE, Gwag BJ. (2012) 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, 122 (5): 952-61. [PMID:22537108]

12. 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]

13. 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.

14. 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

Show »

How to cite this page