Identification and development of mPGES-1 inhibitors: where we are at?

• Published in: Future medicinal chemistry Vol. 3; no. 15; p. 1909
• Main Authors: Chang, Hui-Hua, Meuillet, Emmanuelle J
• Format: Journal Article
• Language: English
• Published: England 01.11.2011
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Intramolecular Oxidoreductases - antagonists & inhibitors; Intramolecular Oxidoreductases - chemistry; Intramolecular Oxidoreductases - metabolism; Microsomes - enzymology; Models, Molecular; Neoplasms - drug therapy; Neoplasms - enzymology; Prostaglandin-E Synthases; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology
• DOI: 10.4155/FMC.11.136

Microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal synthase responsible for the synthesis of the pro-tumorigenic prostaglandin E(2) (PGE(2)). mPGES-1 is overexpressed in a wide variety of cancers. Since its discovery in 1997 by Bengt Samuelsson and collaborators, the enzyme has been the object of over 200 peer-reviewed articles. Although today mPGES-1 is considered a validated and promising therapeutic target for anticancer drug discovery, challenges in inhibitor design and selectivity are such that up to this date there are only a few published records of small-molecule inhibitors targeting the enzyme and exhibiting some in vivo anticancer activity. This review summarizes the structures, and the in vitro and in vivo activities of these novel mPGES-1 inhibitors. Challenges that have been encountered are also discussed.