Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance. (January 2022)

• Record Type: Journal Article
• Authors: Zhang, Yan-Yu; Yao, Yun-Da; Luo, Jin-Fang; Liu, Zhong-Qiu; Huang, Yu-Ming; Wu, Fei-Chi; Sun, Qin-Hua; Liu, Jian-Xin; Zhou, Hua
• Is Part Of: Pharmacological research. Volume 175(2022)
• Publication Date: 2022-01
• Subjects: CIA collagen-II-induced arthritis -- COX cyclooxygenases -- DILI drug-induced liver injury -- dog WB dog whole blood assay -- Gpig WB guinea pig whole blood assay -- HWB human whole blood assay -- KI knock-in -- KO knockout -- mPGES microsomal prostaglandin E2 synthase -- NF-κB nuclear factor κB -- NSAIDs non-steroidal anti-inflammatory drugs -- OA osteoarthritis -- PGD2 prostaglandin D2 -- PGE2 prostaglandin E2 -- PGES prostaglandin E2 synthases -- PGF2α prostaglandin F2α -- PGG2 prostaglandin G2 -- PGI2 prostaglandin I2 -- PGs prostaglandins -- PLA2 phospholipase A2 -- RA rheumatic arthritis -- RM reactive metabolite -- Tmax time of maximal plasma concentration, TXA2, thromboxane A2 -- TXB2 thromboxane B2 -- WT wild-type; Compound Ⅲ (PubChem CID: 67033699) -- Curcumin (PubChem CID: 969516) -- Dexamethasone (PubChem CID: 5743) -- EGCG (PubChem CID: 65064) -- Hyperforin (PubChem CID: 441298) -- ISC 27864 (PubChem CID: 136246033) -- LY3031207 (PubChem CID: 57382526) -- MF-63 (PubChem CID: 16070041) -- MK886 (PubChem CID: 3651377) -- Sinomenine (PubChem CID: 5459308); MPGES-1 -- Phospholipid metabolism -- MPGES-1 inhibitor -- PGE2 -- COX-2 -- Inflammatory disease; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105977
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Inflammation is closely linked to the abnormal phospholipid metabolism chain of cyclooxygenase-2/microsomal prostaglandin E2 synthase-1/prostaglandin E2 (COX-2/mPGES-1/PGE2 ). In clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) as upstream COX-2 enzyme activity inhibitors are widely used to block COX-2 cascade to relieve inflammatory response. However, NSAIDs could also cause cardiovascular and gastrointestinal side effects due to its inhibition on other prostaglandins generation. To avoid this, targeting downstream mPGES-1 instead of upstream COX is preferable to selectively block overexpressed PGE2 in inflammatory diseases. Some mPGES-1 inhibitor candidates including synthetic compounds, natural products and existing anti-inflammatory drugs have been proved to be effective in in vitro experiments. After 20 years of in-depth research on mPGES-1 and its inhibitors, ISC 27864 have completed phase II clinical trial. In this review, we intend to summarize mPGES-1 inhibitors focused on their inhibitory specificity with perspectives for future drug development. Graphical Abstract: ga1