MK-2894 sodium 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 | C₂₅H₂₁F₃NNAO₃S |
| Molecular Weight | 495.48914 |
| Exact Mass | 495.109 |
| CAS # | 1006036-88-9 |
| Related CAS # | MK-2894; 1006036-87-8 |
| PubChem CID | 24953972 |
| Appearance | White to off-white solid powder |
| LogP | 5.148 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 34 |
| Complexity | 731 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | RQRUUNKVGDVBFV-UHFFFAOYSA-M |
| InChi Code | InChI=1S/C25H22F3NO3S.Na/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);/q;+1/p-1 |
| Chemical Name | sodium;4-[1-[[2,5-dimethyl-4-[[4-(trifluoromethyl)phenyl]methyl]thiophene-3-carbonyl]amino]cyclopropyl]benzoate |
| Synonyms | MK-2894 sodium; MK 2894; MK2894 sodium |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 Vivo | MK-2894 sodium salt (oral, 20 mg/kg; intravenous, 5 mg/kg) exhibits good pharmacokinetic characteristics in mice, with moderate bioavailability F = 21% and slow to moderate clearance ( CL=23 mL/min/kg), volume of distribution (Vdss=7.6 L/kg), good elimination half-life (T1/2=15 h) and the maximum concentration reached in mice (Cmax=1.4 μM) [1] . MK-2894 sodium salt (oral, 20 mg/kg; intravenous, 5 mg/kg) exhibits good pharmacokinetic profiles in SD rats, with moderate bioavailability F = 29%, and slow to moderate clearance. rate (CL=9.2 mL/min/kg), volume of distribution (Vdss=2.6 L/kg), good elimination half-life (T1/2=4.5 h) and the maximum concentration reached in mice (Cmax=4.5 μM) [1]. MK-2894 sodium salt (oral, 5 mg/kg; intravenous, 1 mg/kg) exhibits good pharmacokinetic profiles in dogs, with moderate bioavailability F = 32% and slow to moderate clearance (CL =23 mL/min/kg), volume of distribution (Vdss=0.91 L/kg), good elimination half-life (T1/2=8.8 h) and the maximum concentration reached in mice (Cmax=3.3 μM) [1]. MK-2894 sodium salt (oral; 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, demonstrating a response to pain when measured Inhibition of plantar injection of carrageenan 3 hours later [1]. MK-2894 sodium salt (oral; 0.1 mg/kg-10 mg/kg; 5 days) demonstrated potent activity in inhibiting chronic paw swelling of the primary and secondary paws in a dose-dependent manner with an ED50 value of 0.02 mg/ kg/day. In a rat model of adjuvant-induced arthritis, an ED100 of 0.1 mg/kg/day and a plasma concentration of 4 nM completely inhibited secondary paw swelling 24 hours after the final dose [1]. |
| References |
[1]. Structural features of subtype-selective EP receptor modulators. Drug Discov Today. 2017 Jan;22(1):57-71. [2]. 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. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0182 mL | 10.0910 mL | 20.1820 mL | |
| 5 mM | 0.4036 mL | 2.0182 mL | 4.0364 mL | |
| 10 mM | 0.2018 mL | 1.0091 mL | 2.0182 mL |