MK-2894 is a novel, potent and selective antagonist of prostaglandin E2 subtype 4 receptor (PGE2). MK-2894 exhibits a good pharmacokinetic profile in several preclinical species and strong anti-inflammatory effects in multiple animal models of inflammation and pain. Comparing MK-2894 to the conventional NSAID indomethacin, rats also exhibit a favorable GI tolerability profile.

Physicochemical Properties

Molecular Formula	C25H22NO3F3S
Molecular Weight	473.50728
Exact Mass	473.127
Elemental Analysis	C, 63.41; H, 4.68; F, 12.04; N, 2.96; O, 10.14; S, 6.77
CAS #	1006036-87-8
Related CAS #	MK-2894 sodium salt; 1006036-88-9; 1006036-87-8 (free acid)
PubChem CID	24952929
Appearance	White to light brown solid powder
LogP	6.666
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	33
Complexity	725
Defined Atom Stereocenter Count	0
SMILES	O=C(O)C1=CC=C(C2(NC(C3=C(C)SC(C)=C3CC4=CC=C(C(F)(F)F)C=C4)=O)CC2)C=C1
InChi Key	QJZQFVRFJCGDKF-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H22F3NO3S/c1-14-20(13-16-3-7-19(8-4-16)25(26,27)28)21(15(2)33-14)22(30)29-24(11-12-24)18-9-5-17(6-10-18)23(31)32/h3-10H,11-13H2,1-2H3,(H,29,30)(H,31,32)
Chemical Name	4-[1-[[2,5-dimethyl-4-[[4-(trifluoromethyl)phenyl]methyl]thiophene-3-carbonyl]amino]cyclopropyl]benzoic acid
Synonyms	MK 2894; MK-2894; MK2894
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 vitro activity: MK-2894 exhibits inhibitory effects on PGE2-induced cAMP accumulation and the EP4 functional potency in HEK 293 and HWB cells with IC50 values of 2.5 nM and 11 nM, respectively[1].
ln Vivo	MK-2894 (oral administration: 20 mg/kg; intravenous injection: 5 mg/kg) has a good pharmacokinetic profile in mice, with a moderate bioavailability of F=21% and a slow to moderate clearance rate of CL=23 mL/min/kg. It also has a good elimination half-life of T1/2=15 h, a volume of distribution of 7.6 L/kg, and a maximum concentration reached in mice of Cmax=1.4 μM. MK-2894, administered orally at a dose of 20 mg/kg or intravenously at a dose of 5 mg/kg, demonstrates a good pharmacokinetic profile in SD-rats, a moderate bioavailability of 29%, and a slow to moderate clearance rate of 9.2 mL/min/kg. It also has a volume of distribution of 2.6 L/kg, good elimination half-lives of T1/2=4.5 h, and a maximum concentration reached in mice of 4.5 μM[1]. MK-2894 (oral administration, 5 mg/kg; intravenous injection, 1 mg/kg) shows a good pharmacokinetic profile in dogs, with a moderate bioavailability of F=32% and a slow to moderate clearance rate of CL=23 mL/min/kg. In mice, the maximum concentration reached is Cmax=3.3 μM, and the volume of distribution is Vdss=0.91 L/kg.[1] MK-2894 (oral administration; 0.1 mg/kg–10 mg/kg; single dose) exhibits a dose-dependent inhibition of the acute carrageenan-induced mechanical hyperalgesia model in SD rats. It also shows an inhibition of pain response when measured three hours after the carrageenan injection subplantarly[1]. MK-2894 (oral administration; 0.1 mg/kg-10 mg/kg; 5 days) demonstrates strong activity in inhibiting chronic paw swelling in both the primary and secondary paws in a dose-dependent manner, the ED50 value is 0.02 mg/kg/day. In an adjuvant-induced arthritis rat model, 24-hours after the last dose, the plasma concentration of 0.1 mg/kg/day is the point at which the secondary paw swelling is completely inhibited[1].
References	[1]. The discovery of 4-{1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic acid (MK-2894), a potent and selective prostaglandin E2 subtype 4 receptor antagonist. J Med Chem. 2010 Mar 11;53(5):2227-38. [2]. Structural features of subtype-selective EP receptor modulators. Drug Discov Today. 2017 Jan;22(1):57-71.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 50 mg/mL (~105.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 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 (5.28 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.28 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	2.1119 mL	10.5594 mL	21.1189 mL
	5 mM	0.4224 mL	2.1119 mL	4.2238 mL
	10 mM	0.2112 mL	1.0559 mL	2.1119 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.