MF-766 is a potent, selective and orally bioactive EP4 antagonist (inhibitor) with Ki of 0.23 nM. MF-766 behaves as a full antagonist in functional assays with IC50 of 1.4 nM (changes to 1.8 nM in the presence of 10% HS). MF-766 may be utilized in cancer and inflammatory disease study.

Physicochemical Properties

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)

Biological Activity

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].
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].
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.
References	[1]. Discovery of 4-[1-[([1-[4-(trifluoromethyl)benzyl]-1H-indol-7-yl]carbonyl)amino]cyclopropyl]benzoic acid (MF-766), a highly potent and selective EP4 antagonist for treating inflammatory pain. Bioorg Med Chem Lett. [2]. Combination of EP 4 antagonist MF-766 and anti-PD-1 promotes anti-tumor efficacy by modulating both.

Solubility Data

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.