892549-43-8

Basic information

• Product Name: MF-63
• Synonyms: MF-63;2-(9-Chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-1,3-benzenedicarbonitrile;2-(6-chloro-1H-phenanthro-[9,10-d]iMidazol-2-yl)isophthalonitrile;2-(9-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-1,3-Benzenedic
• CAS NO: 892549-43-8
• Molecular Formula: C23H11ClN4
• Molecular Weight: 378.81324
• EINECS: -0
• Mol File: 892549-43-8.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 709.7 °C at 760 mmHg
• Flash Point: 383 °C
• Appearance: /
• Density: 1.49
• Solubility: Soluble in DMSO
• PKA: 11.34±0.30(Predicted)
• CAS DataBase Reference: MF-63(CAS DataBase Reference)
• NIST Chemistry Reference: MF-63(892549-43-8)
• EPA Substance Registry System: MF-63(892549-43-8)

Safety Data

• Hazardous Substances Data: 892549-43-8(Hazardous Substances Data)

Usage

Description

Microsomal prostaglandin E2 synthase-1 (mPGES-1) is the terminal enzyme in the biosynthesis of PGE2. MF63 is a potent, selective, and orally active inhibitor of human mPGES-1 (IC50 = 1.3 nM). It displays greater than 1,000-fold selectivity over other prostanoid synthases. MF63 also potently inhibits guinea pig mPGES-1 (IC50 = 0.9 nM) but not mouse or rat mPGES-1. In guinea pigs or in mice expressing human mPGES-1, MF63 prevents LPS-induced pyresis, hyperalgesia, and iodoacetate-induced osteoarthritic pain. It does not produce the gastrointestinal toxicity that is caused by non-selective COX inhibitors, although it markedly suppresses PGE2 synthesis in the stomach.

Uses

MF 63 is a microsomal prostaglandin E2 synthase-1 (mPGES-1) the final enzyme in the synthesis of PGE2. Prevents LPS-induced hyperglasia. Anti-inflammatory, analgesic, anti-cancer agent.

in vitro

mf63 was found to be significantly more potent than those previously reported mpges-1 inhibitors with an intrinsic inhibitory potency on the recombinant human mpges-1 enzyme. furthermore, mf63 showed a pge2 whole cell inhibition in a549 cells and a human whole blood activity [1].

in vivo

in rodent species, mf63 inhibited guinea pig mpges-1 strongly but not the mouse or rat enzyme. when tested in the guinea pig and a knock-in (ki) mouse expressing human mpges-1, mf63 suppressed the synthesis of pge2 selectively, but not other prostaglandins that were inhibitable by nonsteroidal anti-inflammatory drugs (nsaid), yet remaided nsaid-like efficacy at inhibiting lipopolysaccharide-induced hyperalgesia, pyresis, and iodoacetate-induced osteoarthritic pain. additionally, mf63 did not cause nsaid-like gastrointestinal toxic effects, such as mucosal erosions or leakage in the ki mice or nonhuman primates, although mf63 markedly inhibited pge2 synthesis in the ki mouse stomach [1].

IC 50

0.9 and 1.3 nm for pig mpges-1 and human mpges-1

references

[1] xu d,rowland se,clark p,giroux a,cté b,guiral s,salem m,ducharme y,friesen rw,méthot n,mancini j,audoly l,riendeau d. mf63 [2-(6-chloro-1h-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a selective microsomal prostaglandin e synthase-1 inhibitor, relieves pyresis and pain in preclinical models of inflammation. j pharmacol exp ther.2008 sep;326(3):754-63.