MF-63 is a novel and selective mPGES-1 inhibitor. MF63 potently inhibited the human mPGES-1 enzyme (IC(50) = 1.3 nM), with a high degree (>1000-fold) of selectivity over other prostanoid synthases. In rodent species, MF63 strongly inhibited guinea pig mPGES-1 (IC(50) = 0.9 nM) but not the mouse or rat enzyme. MF63 did not cause NSAID-like gastrointestinal toxic effects, such as mucosal erosions or leakage in the KI mice or nonhuman primates, although it markedly inhibited PGE(2) synthesis in the KI mouse stomach.

Physicochemical Properties

Molecular Formula	C23H11CLN4
Molecular Weight	378.82
Exact Mass	378.067
CAS #	892549-43-8
Related CAS #	892549-43-8;
PubChem CID	16070041
Appearance	Light yellow to yellow solid powder
LogP	5.933
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	1
Heavy Atom Count	28
Complexity	667
Defined Atom Stereocenter Count	0
InChi Key	BVFLHOOKHPFDCT-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H11ClN4/c24-15-8-9-18-19(10-15)16-6-1-2-7-17(16)21-22(18)28-23(27-21)20-13(11-25)4-3-5-14(20)12-26/h1-10H,(H,27,28)
Chemical Name	2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile
Synonyms	MF-63 MF63 MF 63
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	MF63 (0.01-100 µM; 24 h) promotes PGF2α creation in a dose-dependent manner and inhibits 10 ng/mL IL-1β-induced PGE2 synthesis in A549 cells [1]. possesses anti-inflammatory properties and increases the production of various metalloprotein 1 (MT1) isoforms and endogenous antagonists of IL-1 and IL-36 [2].
ln Vivo	MF63 (100 mg/kg; mouse brain; single dosage) suppresses PEG2 production in a dose-dependent manner and decreases the accumulation of PEG2 in the head and brain of KI (mPGES-1 knock-in) mice [1]. A single dose of MF63 (0-150 mg/kg; lateral wall) reduces the dose-dependent hyperalgesia caused by LPS in KI mice [1]. MF63 (0-150 mg/kg; side wall; single dosage) reduces chronic osteoarthritis-like pain, causes hyperalgesia, fever, and PEG2 production [1]. MF63 (0–100 mg/kg; bucally; twice daily for four days) in non-human primates and KI mimics
Animal Protocol	Animal/Disease Models: 10 to 12 weeks of KI and wild-type mice injected with LPS [1]. Animals with gastrointestinal tolerance. Doses: 10 mg/kg and 100 mg/kg. Route of Administration: po (oral gavage); single dose. Experimental Results: Inhibited the accumulation of PGE2 in the air sac and brain of KI mice in a dose-dependent manner and selectively in the brain. Hyperalgesia was diminished by 50% at the 10 mg/kg dose and 80% at the 100 mg/kg dose in KI mice, but had no effect in wild-type mice. Animal/Disease Models: Young male Hartley guinea pig (~250 g) with osteoarthritis pain [1]. Doses: 0, 3, 10, 15, 30, 50, 100 or 150mg/kg. Route of Administration: po (oral gavage); single dose. Experimental Results: Inhibited PGE2 formation, alleviated chronic osteoarthritis-like pain and suppressed fever in a dose-dependent manner. Animal/Disease Models: 10 to 12 weeks old KI mice and non-human primates [1]. Doses: 0, 3, 10, 30 or 100mg/kg. Route of Administration: po (oral gavage); twice (two times) daily for 4 days. Experimental Results: There was no gastrointestinal toxicity in KI mice and non-human primates.
References	[1]. 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. [2]. Regulation of gene expression by MF63, a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes. Br J Pharmacol. 2020 Sep;177(18):4134-4146.

Solubility Data

Solubility (In Vitro)

DMSO : ~75 mg/mL (~197.99 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6398 mL	13.1989 mL	26.3978 mL
	5 mM	0.5280 mL	2.6398 mL	5.2796 mL
	10 mM	0.2640 mL	1.3199 mL	2.6398 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.