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Purity: ≥98%
| Targets |
MF-63 targets microsomal prostaglandin E2 synthase-1 (mPGES-1), an enzyme that catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2). PGE2 is a key mediator of inflammation, pain, and fever. By inhibiting mPGES-1, MF-63 reduces PGE2 production. It shows high selectivity for mPGES-1 over other prostanoid synthases.
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| 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].
In vitro, MF-63 potently inhibits human mPGES-1 with an IC50 of 1.3 nM and pig mPGES-1 with an IC50 of 0.9 nM. It shows >1000-fold selectivity over other prostanoid synthases. It does not inhibit mouse or rat mPGES-1. These activities confirm its potency and selectivity as an mPGES-1 inhibitor. |
| 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
In vivo, MF-63 reduces the accumulation of PGE2. It relieves pyresis (fever), hyperalgesia (pain hypersensitivity), and inflammatory pain by inhibiting mPGES-1. It is orally active. MF-63 does not cause NSAID-like gastrointestinal toxicity. These findings support its potential as a selective anti-inflammatory agent. |
| Enzyme Assay |
In vitro enzyme assays for MF-63 measure mPGES-1 inhibition using recombinant human or pig mPGES-1 enzyme. Enzyme activity is assessed by measuring the conversion of PGH2 to PGE2 using ELISA or mass spectrometry. Various concentrations of MF-63 are added. IC50 values are calculated from dose-response curves. Selectivity against other prostanoid synthases is assessed.
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| Cell Assay |
Cellular assays for MF-63 use cells that express mPGES-1, such as macrophages or fibroblasts. Cells are stimulated with inflammatory stimuli (e.g., LPS, IL-1β) to induce PGE2 production. Various concentrations of MF-63 are added. PGE2 levels in culture media are measured by ELISA. Cytotoxicity is assessed using MTT assays.
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| 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. In vivo animal studies for MF-63 utilize models of inflammation, pain, and fever. The compound is administered orally. Inflammatory pain is assessed by measuring paw withdrawal thresholds. Fever is assessed by measuring body temperature. PGE2 levels are measured in tissues or plasma. Efficacy is compared to vehicle and reference NSAIDs. Gastrointestinal toxicity is assessed. |
| ADME/Pharmacokinetics |
MF-63 has molecular weight of 378.8 g/mol and molecular formula C23H11ClN4. It is also known as 2-(9-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)benzene-1,3-dicarbonitrile. Purity is typically ≥98%. It is typically stored at -20°C. It is soluble in DMSO. It is orally active. Pharmacokinetic properties support once-daily oral dosing.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of MF-63 has been evaluated in standard toxicology studies. Unlike NSAIDs, MF-63 does not cause gastrointestinal toxicity, as it selectively inhibits mPGES-1 without affecting COX-1 or COX-2. Potential adverse effects may include effects on the immune system. No significant toxicity has been reported.
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| References |
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| Additional Infomation |
MF-63 is a selective and orally active mPGES-1 inhibitor. It inhibits human mPGES-1 with an IC50 of 1.3 nM. It shows >1000-fold selectivity over other prostanoid synthases. It relieves inflammatory pain and fever. It is available for research purposes only.
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| Molecular Formula |
C23H11CLN4
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| Molecular Weight |
378.82
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| Exact Mass |
378.067
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| CAS # |
892549-43-8
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| Related CAS # |
892549-43-8;
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| PubChem CID |
16070041
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.933
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
28
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| Complexity |
667
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BVFLHOOKHPFDCT-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile
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| Synonyms |
MF-63 MF63 MF 63
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~75 mg/mL (~197.99 mM)
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| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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