MK-2894_product_DataBase

Bioactivity

MK-2894 is a potent, selective, orally active and high affinity (Ki=0.56 nM) full antagonist against E prostanoid receptor 4 (EP4 receptor) (IC50=2.5 nM). MK-2894 possesses potent anti-inflammatory activity in animal models of pain/inflammation and can be used for the research of arthritis[1][2].

Invitro

MK-2894 shows inhibitory effects on PGE2-induced cAMP accumulation, the EP4 functional potency in HEK 293 and HWB cells with IC50 values of 2.5 nM and 11 nM, respectively[1].

In Vivo

MK-2894 (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 (Vdss=7.6 L/kg), good elimination half-lives (T1/2=15 h) and the maximum concentration reached (Cmax=1.4 μM) in mice[1].MK-2894 (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 (Vdss=2.6 L/kg), good elimination half-lives (T1/2=4.5 h) and the maximum concentration reached (Cmax=4.5 μM) in mice[1].MK-2894 (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 (Vdss=0.91 L/kg), good elimination half-lives (T1/2=8.8 h) and the maximum concentration reached (Cmax=3.3 μM) in mice[1].MK-2894 (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[1].MK-2894 (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 ED50 value is 0.02 mg/kg/day. The complete inhibition of the secondary paw swelling is at an ED100 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[1].

Name

MK-2894

CAS

1006036-87-8

Formula

C25H22F3NO3S

Molar Mass

473.51

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Blouin M, Han Y, Burch J, Farand J, Mellon C, Gaudreault M, Wrona M, Lévesque JF, Denis D, Mathieu MC, Stocco R, Vigneault E, Therien A, Clark P, Rowland S, Xu D, O'Neill G, Ducharme Y, Friesen R. The discovery of 4-{1-[({2,5-dimethyl-4-[4-(trifluorometh [2]. Tijana Markovič, et al. Structural features of subtype-selective EP receptor modulators. Drug Discov Today. 2017 Jan;22(1):57-71.

PeptideDB

MK-2894

CAS: 1006036-87-8 F: C25H22F3NO3S W: 473.51