[CAS NO. 1218918-62-7] MK-7246
PRODUCTS SPECIFICATIONS [1218918-62-7]
DESCRIPTION [1218918-62-7]
Overview
| MDL | MFCD22741619 |
|---|---|
| Molecular Weight | 416.47 |
| Molecular Formula | C21H21FN2O4S |
| SMILES | O=C(O)CC1=C(CC[C@@H](N(S(=O)(C2=CC=C(F)C=C2)=O)C)C3)N3C4=C1C=CC=C4 |
Summary
MK-7246 is a potent and selective CRTH2 antagonist with a K i of 2.5±0.5 nM.
IC50 & Target
|
DP 2.5 nM (Ki) |
TP 3804 nM (Ki) |
In Vitro
The affinity and selectivity of MK-7246 for human CRTH2 and recombinant human prostanoid receptors is determined by equilibrium competition analysis using the relevant radioligands and cell membranes expressing the various receptors. MK-7246 competes for [ 3 H]PGD 2 specific binding to cell membranes expressing recombinant human CRTH2 with high-affinity (K i , 2.5 nM). MK-7246 displays a relatively high selectivity for CRTH2 with an affinity 149-fold lower for the DP receptor (K i , 373±96 nM) and ≥1500-fold lower for the other prostanoid receptors (K i , 7668±2169 nM for EP 2 , 3804±1290 nM for TP). MK-7246 is also tested in a panel of 157 enzyme and receptor assays at concentrations up to 100 μM and small but significant activity is detected only on phosphodiesterase 1 (PDE1, IC 50 =33.2 μM) and MAPK3 (ERK1, IC 50 =49.4 μM) [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Whether the inhibition of a clinically-relevant mechanism of allergic lung inflammation such as CRTH2 will lead to a suppression of inflammatory responses is investigated in A. alternata challenged Brown Norway rats (n=8 per group). Mast cell derived production of Prostaglandin D 2 (PGD 2 ) is believed to be a prime mediator of allergic inflammation. Since CRTH2 plays an important role in the early aspects of the allergic inflammation cascade, the effect of the CRTH2 antagonist is examined on A. alternate elicited pulmonary inflammatory responses. CRTH2 inhibitor MK-7246 is orally administered 1 h before and 23 h post-intratracheal instillation of the A. alternata . MK-7246 produces a dose dependent decrease in the number of eosinophils with a maximal inhibition of 74±5% in the 100 mg/kg group (P<0.05), IL-5 (80±12%) and IL-13 (76±14%) cytokines levels (P<0.05) [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
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 |
Solvent & Solubility
DMSO : 300 mg/mL ( 720.34 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4011 mL | 12.0057 mL | 24.0113 mL |
| 5 mM | 0.4802 mL | 2.4011 mL | 4.8023 mL |
| 10 mM | 0.2401 mL | 1.2006 mL | 2.4011 mL |
References
- [1] Gervais FG, et al. Pharmacological characterization of MK-7246, a potent and selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells) antagonist. Mol Pharmacol. 2011 Jan;79(1):69-76.
- [2] Gil MA, et al. Anti-inflammatory actions of Chemoattractant Receptor-homologous molecule expressed on Th2 by the antagonist MK-7246 in a novel rat model of Alternaria alternata elicited pulmonary inflammation. Eur J Pharmacol. 2014 Nov 15;743:106-16.
