2. Academic Validation
  3. Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance

Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance

  • Pharmacol Res. 2022 Jan;175:105977. doi: 10.1016/j.phrs.2021.105977.
Yan-Yu Zhang 1,  Yun-Da Yao 1,  Jin-Fang Luo 2,  Zhong-Qiu Liu 3,  Yu-Ming Huang 4,  Fei-Chi Wu 4,  Qin-Hua Sun 5,  Jian-Xin Liu 6,  Hua Zhou 7
Affiliations

Affiliations

  • 1 Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Taipa, Macao, PR China.
  • 2 Guizhou University of Traditional Chinese Medicine, Huaxi District, Guiyang City, Guizhou Province 550025, PR China.
  • 3 Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangzhou University of Chinese Medicine, Guangzhou City, Guangdong Province 510006, PR China.
  • 4 Hunan Zhengqing Pharmaceutical Company Group Ltd, Huaihua City, Hunan Province, PR China.
  • 5 School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua City, Hunan Province 418000, PR China. Electronic address: [email protected].
  • 6 School of Public Health, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province 310053, PR China. Electronic address: [email protected].
  • 7 Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Taipa, Macao, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangzhou University of Chinese Medicine, Guangzhou City, Guangdong Province 510006, PR China; Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai City, Guangdong Province 519000, PR China. Electronic address: [email protected].
PMID: 34798265 DOI: 10.1016/j.phrs.2021.105977
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.

Keywords

COX-2; 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); Inflammatory disease; LY3031207 (PubChem CID: 57382526); MF-63 (PubChem CID: 16070041); MK886 (PubChem CID: 3651377); MPGES-1; MPGES-1 inhibitor; PGE(2); Phospholipid metabolism; Sinomenine (PubChem CID: 5459308).

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