| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
DP ( Ki = 2.5 nM ); TP ( Ki = 3804 nM )
MK-7246 targets CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), also known as DP2 or GPR44. CRTH2 is a G protein-coupled receptor that is expressed on Th2 cells, eosinophils, and basophils, and is activated by prostaglandin D2 (PGD2). PGD2 is a lipid mediator produced during allergic inflammation. By antagonizing CRTH2, MK-7246 blocks PGD2-induced chemotaxis and activation of Th2 cells and other inflammatory cells, thereby reducing allergic inflammation. |
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| ln Vitro |
Equilibrium competition analysis, employing pertinent radioligands and cell membranes expressing the different receptors, is used to determine the affinity and selectivity of MK-7246 for human CRTH2 and recombinant human prostanoid receptors. High-affinity [3H]PGD2 specific binding is competitively bound (Ki, 2.5 nM) by MK-7246 to cell membranes expressing recombinant human CRTH2. MK-7246 exhibits a relatively high selectivity for CRTH2 with an affinity 149-fold lower for the DP receptor (Ki, 373±96 nM) and ≥1500-fold lower for the other prostanoid receptors (Ki, 7668±2169 nM for EP2, 3804±1290 nM for TP). Additionally, MK-7246 is examined in a panel of 157 enzyme and receptor tests at concentrations up to 100 μM; only phosphodiesterase 1 (PDE1, IC50=33.2 μM) and MAPK3 (ERK1, IC50=49.4 μM) exhibit slight but noteworthy activity[1].
In vitro, MK-7246 demonstrates potent and selective antagonistic activity against CRTH2. Specific IC50 values for receptor binding or functional inhibition are not detailed in the available sources. The compound was discovered as a selective CRTH2 antagonist for the treatment of respiratory diseases. Its activity has been characterized in receptor binding and functional assays. Specific cellular assay data, such as IC50 values for inhibition of PGD2-induced chemotaxis, are not detailed in the available sources. |
| ln Vivo |
The purpose of this study is to determine whether reducing inflammatory responses in A. alternata-challenged Brown Norway rats (n = 8 per group) results from blocKing a clinically-relevant mechanism of allergic lung inflammation, such as CRTH2. One major theory for the cause of allergic inflammation is the production of prostaglandin D2 (PGD2) by mast cells. 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. Oral CRTH2 inhibitor MK-7246 is given one hour prior to and twenty-three hours following the A. alternata's intratracheal instillation. The number of eosinophils is reduced in a dose-dependent manner by MK-7246, with a maximum inhibition of 74±5% in the 100 mg/kg group (P<0.05), and a dose-dependent decrease in IL-5 (80±12%) and IL-13 (76±14%) cytoKine levels (P<0.05) [2].
Specific in vivo activity data for MK-7246 are not detailed in the available sources. As a CRTH2 antagonist, the compound was developed for the treatment of respiratory diseases, suggesting that it has shown efficacy in preclinical models of allergic inflammation and asthma. However, specific animal model studies have not been described in the available literature. The compound is intended for research use only. |
| Enzyme Assay |
Recombinant HEK293E cell membranes are used to characterize the binding Kinetics of [3H]MK-7246 (specific activity, 41 Ci/mmol) at human CRTH2. The incubation mixture contains 10 mM MgCl2 instead of MnCl2, 10 nM [3H]MK-7246, and 1.25 μg of membrane protein. These are the radioligand binding experimental conditions for CRTH2. Specific binding at equilibrium correlated with 85–95% of total binding, while total binding accounts for 10% of the radioligand additions to the incubation media. The membranes are first incubated with 10 μM MK-7246 for 120 min, either in the presence (nonspecific binding) or absence (total binding) of [3H]MK-7246. To start the dissociation of the radioligand from the receptor, add 10 μM MK-7246 or 100 μM PGD2 to one series of total binding incubation tubes. Allow the reaction to continue for up to 300 minutes. After that, the samples are collected and handled as previously mentioned. The observed on rate (Kobs) and dissociation rate (Koff) constants, as well as the t1/2 of on and off rates, are found by nonlinear regression curve-fitting with Prism software for the analysis of the association and dissociation Kinetic data[1].
The CRTH2 binding assay for MK-7246 involves incubating the compound with membrane preparations from cells expressing the human CRTH2 receptor and a radiolabeled PGD2 ligand (such as [³H]-PGD2 or a related compound). After incubation at room temperature for an appropriate period, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 or Ki for displacement of the radioligand is calculated from the competition curve. Functional antagonism can be assessed using calcium mobilization or chemotaxis assays. |
| Cell Assay |
To evaluate the cellular activity of MK-7246, cells expressing the human CRTH2 receptor (such as CHO or HEK293 cells, or primary human Th2 cells or eosinophils) are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye. Cells are pre-incubated with varying concentrations of MK-7246 and then stimulated with PGD2 or a selective CRTH2 agonist. The intracellular calcium flux is measured using a fluorescence plate reader. The IC50 for inhibition of PGD2-induced calcium flux is calculated. Chemotaxis assays can also be performed using Transwell chambers to assess the compound's ability to inhibit PGD2-induced cell migration.
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| Animal Protocol |
Rats: Oral Budesonide (3 mg/kg) is given 2 hours before and 22 hours after the A. alternata extract instillation, while intratracheal Budesonide is dosed 1 hour before and 23 hours after the A. alternate intratracheal dose. Budesonide administered intratracheally is prepared. To investigate the impact of the CRTH2 antagonist on A. alternata elicited pulmonary inflammatory responses, MK-7246 (3, 10, 30, and 100 mg/kg) is given orally 1 hour prior to and 23 hours following an A. alternata extract instillation. In both experiments, an oral dose of budesonide is used as a positive control. The animals are given a 3% isoflurane mild anesthesia (supplemented with 100% oxygen) either two hours after an oral dose or one hour after an intratracheal dose. In order to make it easier to locate the tracheal and larynx apertures, the animals are additionally fastened to a rodent work stand. A microsprayer is used to deliver 0.1 mL of 10,000 μg/mL (1000 μg total) A. alternata extract after inserting the needle into the trachea. After being kept under observation while they recover from anesthesia, the animals are placed back in their cages where they are given unlimited access to food and water.
Specific in vivo animal experiment protocols for MK-7246 are not detailed in the available sources. As a CRTH2 antagonist, the compound would typically be evaluated in animal models of allergic inflammation and asthma, such as ovalbumin-induced airway inflammation models in mice or rats. Animals would be sensitized and challenged with ovalbumin, and MK-7246 would be administered orally or intraperitoneally. Airway inflammation would be assessed by measuring inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF), airway hyperresponsiveness, and Th2 cytokine levels. However, specific protocols are not described in the available literature. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for MK-7246 are not provided in the available sources. The compound is a small molecule with a molecular weight of 416.47 and a molecular formula of C21H21FN2O4S. It is soluble in DMSO. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma concentrations over time using LC-MS/MS to determine key PK parameters, such as half-life, bioavailability, and clearance.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK-7246 are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is available with a purity of ≥97%. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment.
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| References |
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| Additional Infomation |
MK-7246 is a highly potent, selective antagonist of the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2, also known as DP2 or GPR44). It was discovered for the treatment of respiratory diseases. The compound has a molecular formula of C21H21FN2O4S and a molecular weight of 416.47. Its chemical name is (R)-2-(7-(4-Fluoro-N-methylphenylsulfonamido)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetic acid.
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| Molecular Formula |
C21H21FN2O4S
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|---|---|
| Molecular Weight |
416.4658
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| Exact Mass |
416.121
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| Elemental Analysis |
C, 60.56; H, 5.08; F, 4.56; N, 6.73; O, 15.37; S, 7.70
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| CAS # |
1218918-62-7
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| Related CAS # |
MK-7246 S enantiomer; 2310135-53-4
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| PubChem CID |
45268455
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| Appearance |
White to off-white solid powder
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| LogP |
4.123
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
704
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S(C1C([H])=C([H])C(=C([H])C=1[H])F)(N(C([H])([H])[H])[C@]1([H])C([H])([H])C([H])([H])C2=C(C([H])([H])C(=O)O[H])C3=C([H])C([H])=C([H])C([H])=C3N2C1([H])[H])(=O)=O
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| InChi Key |
JTCAGRAKUAAYDY-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C21H21FN2O4S/c1-23(29(27,28)16-9-6-14(22)7-10-16)15-8-11-20-18(12-21(25)26)17-4-2-3-5-19(17)24(20)13-15/h2-7,9-10,15H,8,11-13H2,1H3,(H,25,26)/t15-/m1/s1
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| Chemical Name |
2-[(7R)-7-[(4-fluorophenyl)sulfonyl-methylamino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetic acid
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| Synonyms |
MK7246; MK 7246; MK-7246
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~300 mg/mL (~720.3 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.75 mg/mL (9.00 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 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: 3.75 mg/mL (9.00 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 37.5 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. View More
Solubility in Formulation 3: 3.75 mg/mL (9.00 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 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 |
*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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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