| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
MF-766 targets the prostaglandin E2 receptor subtype 4 (EP4), a G protein-coupled receptor that mediates the effects of prostaglandin E2 (PGE2). The compound binds to EP4 with a Ki of 0.23 nM. In functional assays, MF-766 behaves as a full antagonist with an IC₅₀ of 1.4 nM (shifted to 1.8 nM in the presence of 10% human serum). MF-766 displays >7,000-fold selectivity for EP4 over all other prostanoid receptor subtypes (EP1, EP2, EP3, DP1, CRTH2/DP2, IP, TP, FP) with Ki values >6,000 nM. By blocking EP4, MF-766 reverses PGE2-induced immunosuppression and inflammation. The EP4 receptor is involved in various physiological and pathological processes, including inflammation, pain, cancer, and immune regulation. MF-766's high potency and selectivity make it a valuable tool for studying the role of EP4 signaling in health and disease.
|
|---|---|
| ln Vitro |
In human NK cells, MF-766 (0.01-10 μM; 1 hour off, stimulated with 50 ng/mL IL-2; with and 0.33 μM PGE2; 18 hours) recovers PGE2 and then IFN-γ without inhibition. MF-766 does not influence the activity of NK cells [2].
In vitro, MF-766 demonstrates potent antagonism of EP4-mediated responses. The compound binds to EP4 with a Ki of 0.23 nM and behaves as a full antagonist with an IC₅₀ of 1.4 nM (shifted to 1.8 nM in the presence of 10% human serum) in functional assays. MF-766 displays >7,000-fold selectivity for EP4 over all other prostanoid receptor subtypes. In cellular assays, MF-766 (0.01-10 μM) reverses PGE2-induced suppression of IFN-γ secretion in human NK cells without affecting cell viability. The compound's ability to reverse PGE2-induced immunosuppression suggests potential applications in cancer immunotherapy. MF-766's high potency and selectivity make it a valuable tool for studying the role of EP4 in various cellular and physiological processes. The compound's effects on cell viability, proliferation, and immune function can be assessed in various cell types. |
| ln Vivo |
In the CT26 model, MF-766 (medial gavage; 30 mg/kg; once daily; tumor day 21) showed 49% tumor inhibition. EMT6 and 4T1 tumor models, on the other hand, did not exhibit any appreciable differences [2 MF-766 (oral gavage; 30 mg/kg coupled with anti-PD-1 mDX400; once daily; 21 days; q4dx8) in several preclinical models Shows strong anti-tumor efficacy. Tumor inhibition rates were 89%, 66%, and 40%, respectively, in 4T1 tumor models, EMT6 tumors, and CT26 tumors [2].
In vivo, MF-766 demonstrates efficacy in various animal models of cancer and inflammation. The compound is orally active and has good pharmacokinetic properties. MF-766 exhibits unprecedented in vivo potency in the rat AIA (adjuvant-induced arthritis) model. In the CT26 tumor model, MF-766 (oral gavage; 30 mg/kg; once daily; 21 days) exhibits 49% tumor growth inhibition. In combination with anti-PD-1 antibody, the tumor growth inhibition rate reaches 89%, 66%, and 40% in CT26, EMT6, and 4T1 models, respectively. These results suggest that EP4 antagonism can enhance the efficacy of immune checkpoint blockade. The compound's oral bioavailability and in vivo efficacy make it a valuable tool for studying the role of EP4 signaling in cancer and inflammation and for validating EP4 as a therapeutic target. |
| Enzyme Assay |
In vitro receptor binding assays for MF-766 employ radioligand displacement techniques using membrane preparations from cells expressing the EP4 receptor or other prostanoid receptors. The assay involves incubating MF-766 at varying concentrations with the membrane preparation and a fixed concentration of a radiolabeled prostanoid receptor ligand, such as [³H]-PGE2. Following incubation, bound and free radioligand are separated by rapid filtration through glass fiber filters, and the radioactivity retained on the filters is measured by scintillation counting. Non-specific binding is determined in the presence of a high concentration of unlabeled PGE2 or a prostanoid receptor antagonist. Binding affinity (Ki) values are calculated from competition curves using nonlinear regression analysis. For selectivity profiling, MF-766 is tested against EP1, EP2, EP3, DP1, CRTH2/DP2, IP, TP, and FP receptors using similar methodologies. For functional assays, cells expressing EP4 are stimulated with PGE2 in the presence or absence of MF-766, and downstream signaling such as cAMP accumulation is measured.
|
| Cell Assay |
In vitro cellular assays for MF-766 typically employ cell lines expressing the EP4 receptor or primary cells that respond to PGE2. For studies investigating immune modulation, human NK cells are cultured in appropriate media and treated with MF-766 (0.01-10 μM) in the presence or absence of PGE2. IFN-γ secretion is measured by ELISA or flow cytometry. Cell viability is assessed using standard assays such as MTT or resazurin reduction. For studies investigating the role of EP4 in cancer, cancer cell lines are treated with MF-766 alone or in combination with other agents, and cell proliferation, apoptosis, and signaling pathways are assessed. The compound's effects on cAMP accumulation can be measured using ELISA or FRET-based assays. The compound's selectivity for EP4 over other prostanoid receptors can be confirmed using cells expressing each receptor subtype.
|
| Animal Protocol |
Animal/Disease Models: Female C57BL/6 J strain mice were subcutaneously (sc) (sc) injected with CT26, EMT6 or 4T1 cells [2]
Doses: 30 mg/kg combined with anti-PD-1 mDX400: po (oral gavage); 10 mg/kg or 30 mg/kg kg in combination with anti-PD-1 mDX400; one time/day; day 21; q4dx8 Experimental Results: Antitumor activity was improved with PD-1 blockade in multiple syngeneic models. In vivo animal experiments for MF-766 employ various models of cancer and inflammation. For cancer studies, immunocompetent mice bearing syngeneic tumors (CT26, EMT6, 4T1) are treated with MF-766 (oral gavage; 30 mg/kg; once daily) alone or in combination with anti-PD-1 antibody. Tumor growth is measured using calipers, and tumor growth inhibition is calculated. For inflammation studies, the rat AIA (adjuvant-induced arthritis) model is used. Paw swelling and inflammatory markers are assessed. For pharmacokinetic studies, animals are administered MF-766 orally, and plasma concentrations are measured over time. Dosing regimens vary depending on the experimental objectives, with once-daily oral administration being common. The compound's oral bioavailability and in vivo efficacy have been demonstrated in these models. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of MF-766 are characteristic of an orally active small molecule. The compound is orally bioavailable and has good pharmacokinetic properties. MF-766 has a molecular weight of 478.46 and is soluble in DMSO. It exhibits unprecedented in vivo potency in the rat AIA model. The compound's pharmacokinetic profile in terms of absorption, distribution, metabolism, and excretion is consistent with its use as an oral research tool. MF-766 has been shown to be orally active in animal models, with efficacy observed at doses of 30 mg/kg. The compound's half-life and bioavailability have been characterized in preclinical studies. The compound is a second-generation EP4 antagonist engineered to have improved stability compared to first-generation compounds.
|
| Toxicity/Toxicokinetics |
The toxicity profile of MF-766 has not been extensively characterized in the literature, as the compound is primarily used as a research tool. In cellular assays, MF-766 (0.01-10 μM) reverses PGE2-induced suppression of IFN-γ secretion in human NK cells without affecting cell viability. In animal studies, MF-766 has been administered at doses of 30 mg/kg orally without reports of significant toxicity. The compound's safety in humans has not been established, as it has not been developed for clinical use. As with any research compound, appropriate safety precautions should be taken when handling MF-766. The compound's potential for off-target effects or drug-drug interactions has not been extensively studied. The compound is intended for research use only and is not approved for human therapeutic use.
|
| References |
|
| Additional Infomation |
MF-766 is a highly potent, selective, and orally active EP4 antagonist with a Ki of 0.23 nM. It behaves as a full antagonist with an IC₅₀ of 1.4 nM (shifted to 1.8 nM in the presence of 10% human serum) in functional assays. MF-766 displays >7,000-fold selectivity for EP4 over all other prostanoid receptor subtypes. It has a molecular weight of 478.46 and is soluble in DMSO. In vivo, MF-766 (30 mg/kg; oral; once daily; 21 days) exhibits 49% tumor growth inhibition in the CT26 tumor model; in combination with anti-PD-1 antibody, TGI% reaches 89%, 66%, and 40% in CT26, EMT6, and 4T1 models, respectively. MF-766 is a second-generation EP4 antagonist engineered to replace the hydrolytically unstable acylsulfonamide moiety present in first-generation compounds. It is a research compound for cancer and inflammation studies without regulatory approval.
|
| Molecular Formula |
C27H21F3N2O3
|
|---|---|
| Molecular Weight |
478.4712
|
| Exact Mass |
478.15
|
| CAS # |
1050656-06-8
|
| PubChem CID |
25003075
|
| Appearance |
Off-white to gray solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
711.4±60.0 °C at 760 mmHg
|
| Flash Point |
384.1±32.9 °C
|
| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
| Index of Refraction |
1.628
|
| LogP |
5.12
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
35
|
| Complexity |
783
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
BWXAZFCPGFKANL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H21F3N2O3/c28-27(29,30)21-8-4-17(5-9-21)16-32-15-12-18-2-1-3-22(23(18)32)24(33)31-26(13-14-26)20-10-6-19(7-11-20)25(34)35/h1-12,15H,13-14,16H2,(H,31,33)(H,34,35)
|
| Chemical Name |
4-[1-[[1-[[4-(trifluoromethyl)phenyl]methyl]indole-7-carbonyl]amino]cyclopropyl]benzoic acid
|
| Synonyms |
MF766; MF 766; MF-766
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~104.50 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.23 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 | 2.0900 mL | 10.4500 mL | 20.9000 mL | |
| 5 mM | 0.4180 mL | 2.0900 mL | 4.1800 mL | |
| 10 mM | 0.2090 mL | 1.0450 mL | 2.0900 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
