Open AccessEP2 Antagonists (2011–2021): A Decade’s Journey from Discovery to Therapeutics
Author(s) -
Madison N. Sluter,
Hou R,
Lexiao Li,
Nelufar Yasmen,
Ying Yu,
Jiawang Liu,
Jianxiong Jiang
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c00816
Subject(s) - prostaglandin e2 receptor , prostanoid , drug discovery , inflammation , receptor , chemistry , cyclooxygenase , prostaglandin e2 , drug development , pharmacology , drug , neuroscience , immunology , medicine , biology , biochemistry , enzyme , agonist
In the wake of health disasters associated with the chronic use of cyclooxygenase-2 (COX-2) inhibitor drugs, it has been widely proposed that modulation of downstream prostanoid synthases or receptors might provide more specificity than simply shutting down the entire COX cascade for anti-inflammatory benefits. The pathogenic actions of COX-2 have long been thought attributable to the prostaglandin E2 (PGE 2 ) signaling through its Gα s -coupled EP2 receptor subtype; however, the truly selective EP2 antagonists did not emerge until 2011. These small molecules provide game-changing tools to better understand the EP2 receptor in inflammation-associated conditions. Their applications in preclinical models also reshape our knowledge of PGE 2 /EP2 signaling as a node of inflammation in health and disease. As we celebrate the 10-year anniversary of this breakthrough, the exploration of their potential as drug candidates for next-generation anti-inflammatory therapies has just begun. The first decade of EP2 antagonists passes, while their future looks brighter than ever.