MK-2894 sodium salt is a potent, selective, orally active and high affinity ( K i =0.56 nM) full antagonist against E prostanoid receptor 4 (EP4 receptor) ( IC 50 =2.5 nM). MK-2894 sodium salt possesses potent anti-inflammatory activity in animal models of pain/inflammation and can be used for the research of arthritis.
In Vivo
MK-2894 sodium salt (oral administration, 20 mg/kg; intravenous injection, 5 mg/kg) exhibits a favorable pharmacokinetic profile in mice, the moderate bioavailability F=21%, and slow to moderate clearance rate (CL=23 mL/min/kg), the volume of distribution (V dss =7.6 L/kg), good elimination half-lives (T 1/2 =15 h) and the maximum concentration reached (C max =1.4 μM) in mice . MK-2894 sodium salt (oral administration, 20 mg/kg; intravenous injection, 5 mg/kg) exhibits a favorable pharmacokinetic profile in SD-rats, the moderate bioavailability F=29%, and slow to moderate clearance rate (CL=9.2 mL/min/kg), the volume of distribution (V dss =2.6 L/kg), good elimination half-lives (T 1/2 =4.5 h) and the maximum concentration reached (C max =4.5 μM) in mice . MK-2894 sodium salt (oral administration, 5 mg/kg; intravenous injection, 1 mg/kg) exhibits a favorable pharmacokinetic profile in dogs, the moderate bioavailability F=32%, and slow to moderate clearance rate (CL =23 mL/min/kg), the volume of distribution (V dss =0.91 L/kg), good elimination half-lives (T 1/2 =8.8 h) and the maximum concentration reached (C max =3.3 μM) in mice . MK-2894 sodium salt (oral administration; 0.1 mg/kg-10 mg/kg; single dose) inhibits the acute carrageenan-induced mechanical hyperalgesia model in SD rats in a dose-dependent manner, it displays a inhibition of pain response when measured at 3 h post subplantar injection of carrageenan . MK-2894 sodium salt (oral administration; 0.1 mg/kg-10 mg/kg;5 days) exhibits potent activity in inhibiting chronic paw swelling, in both the primary paw and the secondary paw, in a dose-dependent manner, the ED 50 value is 0.02 mg/kg/day. The complete inhibition of the secondary paw swelling is at an ED 100 of 0.1 mg/kg/day with a plasma concentration of 4 nM at 24 h after the final dose in an adjuvant-induced arthritis rat model . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
