PF-9184

Short Summary : microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor

Category : Neuroscience|mPEGS-1

Purity : 0.98

CAS Number : 1221971-47-6

Formula : C21H14Cl2N2O4S

Molecular Weight :

Molecular Weight : 461.3

SMILE : OC1=C(C(NC2=CC=C(C3=CC=C(Cl)C(Cl)=C3)C=C2)=O)NS(C4=CC=CC=C41)(=O)=O

Solubility : Soluble in DMSO

Storage : Store at -20°C

Description : PF-9184 is a novel mPGES-1 inhibitor [1]. Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. mPGES-1 functions as the central switch during immune-induced pyresis and as a target for treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain [2]. mPGES-1 has been incolved in the formation of PGE2 essential for pain hypersensitivity and inflammation. Microsomal prostaglandin E synthase-1 (mPGES-1) has been involved in converting the COX product prostaglandin H2 (PGH2) into the biologically active PGE2[3]. In vitro: PF-9184 potently inhibited recombinant human mPGES-1 with an IC50 value of 16.5 3.8 nM. PF-9184 showed no effect on rhCOX-1 and rhCOX-2 with >6500-fold selectivity. In rationally designed cell systems, PF-9184 inhibited PGE2 synthesis with IC50 in the range of 0.5C5 M in serum-free cell and human whole blood cultures, while sparing the synthesis of 6-keto-PGF1 (PGF1) and PGF2[1]. PF-9184 showed no apparent cytotoxic effects up to 100 M [1].References:[1] Mbalaviele G, Pauley A M, Shaffer A F, et al. Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor[J]. Biochemical pharmacology, 2010, 79(10): 1445-1454.[2] Engblom D, Saha S, Engstrm L, et al. Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis[J]. Nature neuroscience, 2003, 6(11): 1137-1138.[3] Jakobsson P J, Thorn S, Morgenstern R, et al. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target[J]. Proceedings of the National Academy of Sciences, 1999, 96(13): 7220-7225.

Download datasheet