|show drug details|
|5-Heptenoic acid, 7-[3-hydroxy-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl]-|
|Prosta-5,13-dien-1-oic acid, (5Z,11.alpha.,13E,15S)-11,15-dihydroxy-9-oxo-|
|Prosta-5,13-dien-1-oic acid, 11,15-dihydroxy-9-oxo-,|
|Prosta-5,13-dien-1-oic acid, 11,15-dihydroxy-9-oxo-, (5Z,11.alpha.,13E,15S)-|
|Prosta-5,13-dien-1-oic acid, 11,5-dihydroxy-9-oxo-, (5Z,11.alpha.,13E,15S)-|
|nocturnal leg cramps||0|
|Ki: ||Kd:||Ic 50:||Ec50/Ic50:|
Prostaglandin E synthase: a novel drug target for inflammation and cancer.. Makoto Murakami; Ichiro Kudo (2006) Current pharmaceutical design display abstract
Prostaglandin E synthase (PGES), which converts cyclooxygenase (COX)-derived prostaglandin (PG) H(2) to PGE(2), occurs in multiple forms with distinct enzymatic properties, modes of expression, cellular and subcellular localizations and intracellular functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein belonging to the MAPEG (for membrane-associated proteins involved in eicosanoid and GSH metabolism) family. This enzyme is markedly induced by proinflammatory stimuli, is down-regulated by anti-inflammatory glucocorticoids, and is functionally coupled with cyclooxygenase (COX)-2 in marked preference to COX-1. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate PGE(2) production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes. In particular, recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs.
Membrane prostaglandin E synthase-1: a novel therapeutic target.. Bengt Samuelsson; Ralf Morgenstern; Per-Johan Jakobsson (2007) Pharmacological reviews display abstract
Prostaglandin E(2) (PGE(2)) is the most abundant prostaglandin in the human body. It has a large number of biological actions that it exerts via four types of receptors, EP1-4. PGE(2) is formed from arachidonic acid by cyclooxygenase (COX-1 and COX-2)-catalyzed formation of prostaglandin H(2) (PGH(2)) and further transformation by PGE synthases. The isomerization of the endoperoxide PGH(2) to PGE(2) is catalyzed by three different PGE synthases, viz. cytosolic PGE synthase (cPGES) and two membrane-bound PGE synthases, mPGES-1 and mPGES-2. Of these isomerases, cPGES and mPGES-2 are constitutive enzymes, whereas mPGES-1 is mainly an induced isomerase. cPGES uses PGH(2) produced by COX-1 whereas mPGES-1 uses COX-2-derived endoperoxide. mPGES-2 can use both sources of PGH(2). mPGES-1 is a member of the membrane associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily. It requires glutathione as an essential cofactor for its activity. mPGES-1 is up-regulated in response to various proinflammatory stimuli with a concomitant increased expression of COX-2. The coordinate increased expression of COX-2 and mPGES-1 is reversed by glucocorticoids. Differences in the kinetics of the expression of the two enzymes suggest distinct regulatory mechanisms for their expression. Studies, mainly from disruption of the mPGES-1 gene in mice, indicate key roles of mPGES-1-generated PGE(2) in female reproduction and in pathological conditions such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis. These findings indicate that mPGES-1 is a potential target for the development of therapeutic agents for treatment of several diseases.