1221971-47-6

Basic information

• Product Name: PF-9184
• Synonyms: PF-9184
• CAS NO: 1221971-47-6
• Molecular Formula: C₂₁H₁₄Cl₂N₂O₄S
• Molecular Weight: 461.31786
• Mol File: 1221971-47-6.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• Solubility: ≤15mg/ml in DMSO;20mg/ml in dimethyl formamide
• CAS DataBase Reference: PF-9184(CAS DataBase Reference)
• NIST Chemistry Reference: PF-9184(1221971-47-6)
• EPA Substance Registry System: PF-9184(1221971-47-6)

Safety Data

• Hazardous Substances Data: 1221971-47-6(Hazardous Substances Data)

Usage

Description

PF-9184 is a potent inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1), an enzyme that plays a crucial role in the inflammatory response by converting prostaglandin H2 (PGH2) into the biologically active prostaglandin E2 (PGE2). The expression of mPGES-1 is induced by pro-inflammatory mediators such as lipopolysaccharide (LPS), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). PF-9184 exhibits high selectivity for mPGES-1, with at least 6,500-fold selectivity over COX-1 and COX-2.

Uses

Used in Pharmaceutical Industry:
PF-9184 is used as an anti-inflammatory agent for its ability to inhibit mPGES-1, thereby blocking the synthesis of PGE2 in LPS-treated human whole blood and in IL-1β-stimulated fibroblasts. This makes it a promising candidate for the development of anti-inflammatory drugs, particularly in conditions where the inflammatory response is mediated by mPGES-1.
Used in Research Applications:
PF-9184 is used as a research tool for studying the role of mPGES-1 in various inflammatory processes and for understanding the underlying mechanisms of PGE2 synthesis. Its high selectivity for mPGES-1 makes it a valuable compound for investigating the enzyme's function and potential therapeutic targets in inflammation-related diseases.

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 0.5–5 μm in serum-free cell and human whole blood cultures, while sparing the synthesis of 6-keto-pgf1α (pgf1α) and pgf2α[1]. pf-9184 showed no apparent cytotoxic effects up to 100 μm [1].

Enzyme inhibitor

This potent mPGES-1 inhibitor (FW = 461.32 g/mol; CAS 1221971-47-6; Solubility: 100 mM in DMSO), also named N-[3',4'-dichloro(1,1'- biphenyl)yl]-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), targets human and rat microsomal prostaglandin E synthase 1, with respective IC50 values of 16.5 nM and 1.08 μM, exhibiting >6500x selectivity toward mPGES-1 versus COX1 and COX2. PF-9184 inhibits IL- 1β-induced PGE2 synthesis in vitro. In inflammation and clinically relevant biological systems, mPGES-1 expression, like COX-2 expression is induced in cell context- and time-dependent manner, a behavior that is fully consistent with the kinetics of PGE2 synthesis

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, thorén 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.

Upstream product

• 926223-12-3 3',4'-dichloro-1,1'-biphenyl-4-amine 
• 35511-14-9 methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 

Relevant articles and documents

Selective inducible microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors derived from an oxicam template

Here we describe the SAR of a series of potent and selective mPGES-1 inhibitors based on an oxicam template. Compound 13j demonstrated low nanomolar mPGES-1 inhibition in an enzyme assay. In addition, it displayed PGE2 inhibition in a cell-based assay (0.42 μM) and had over 238-fold selectivity for mPGES-1 over COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF1α.