MK-7246
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 525701

CAS#: 1218918-62-7

Description: MK-7246 is a potent and selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells) antagonist. MK-7246 has high affinity for the human, monkey, dog, rat, and mouse CRTH2. MK-7246 interacts with CRTH2 in a reversible manner, MK-7246 exhibits high selectivity over all prostanoid receptors as well as 157 other receptors and enzymes, MK-7246 acts as a full antagonist on recombinant and endogenously expressed CRTH2, MK-7246 demonstrates good oral bioavailability and metabolic stability in various animal species, MK-7246 yields ex vivo blockade of CRTH2 on eosinophils in monkeys and sheep. MK-7246 significantly blocks antigen-induced late-phase bronchoconstriction and airway hyper-responsiveness in sheep.

Chemical Structure

img
MK-7246
CAS# 1218918-62-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 525701
Name: MK-7246
CAS#: 1218918-62-7
Chemical Formula: C21H21FN2O4S
Exact Mass: 416.12
Molecular Weight: 416.467
Elemental Analysis: C, 60.56; H, 5.08; F, 4.56; N, 6.73; O, 15.37; S, 7.70

Price and Availability

Size Price Availability Quantity
2mg USD 160 Ready to ship
5mg USD 350 Ready to ship
10mg USD 650 Ready to ship
25mg USD 1150 Ready to ship
50mg USD 1850 Ready to ship
100mg USD 2450 Ready to ship
200mg USD 3250 Ready to ship
500mg USD 6450 Ready to ship
Bulk inquiry

Synonym: MK7246; MK 7246; MK-7246

IUPAC/Chemical Name: (R)-2-(7-((4-fluoro-N-methylphenyl)sulfonamido)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetic acid

InChi Key: JTCAGRAKUAAYDY-OAHLLOKOSA-N

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

SMILES Code: O=C(O)CC1=C(CC[C@@H](N(S(=O)(C2=CC=C(F)C=C2)=O)C)C3)N3C4=C1C=CC=C4

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: MK-7246 is a potent and selective CRTH2 antagonist with a Ki of 2.5±0.5 nM.
In vitro activity: The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [11C]MK-7246 was evaluated in in vitro cell lines. GPR44-overexpressing CHO-K1 frozen sections showed a significantly higher binding of [11C]MK-7246 (uptake signal = 43.91 ± 14.67 Bq/MBqinj, n = 12) compared with the nontransfected CHO-K1 negative control (uptake signal = 8.74 ± 1.83 Bq/MBqinj, n = 8) (p < 0.05). As expected, the binding could be blocked in the CHO-K1 sections overexpressing GPR44 by coincubation of the nonradioactive MK-7246 compound (p < 0.05) (Figure 2). More importantly, specificity of the binding was repeatedly demonstrated through a decrease in binding after coincubation with excess nonradioactive MK-7246, after which the radiolabeled [11C]MK-7246 displayed the same binding properties as the unlabeled nonradioactive MK7246. Reference: Biomedicines. 2021 Apr; 9(4): 434. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073488/
In vivo activity: Since CRTH2 plays an important role in the early aspects of the allergic inflammation cascade (Kostenis and Ulven, 2006), the effect of the CRTH2 antagonist on A. alternata elicited pulmonary inflammatory responses was examined. The CRTH2 inhibitor MK-7246 was orally adminstered, 1 h before and 23 h post-intratracheal instillation of the A. alternata. The MK-7246 produced a dose dependent decrease in the number of eosinophils with a maximal inhibition of 74±5% in the 100 mg kg−1 group (P<0.05) (Fig. 8 a), IL-5 (80±12%) and IL-13 (76±14%) cytokines levels (P<0.05) (Fig. 8 B and C). The results reported show BAL fluid recovered from BN rats 48 h following the intratracheal. challenge with A. alternata. Moreover, it has been demonstrated for the first time that the CRTH2 antagonist can reduce eosinophilia, most likely through inhibiting ILC2 mediated responses in the A. alternata model. Reference: Eur J Pharmacol. 2014 Nov 15;743:106-16. https://pubmed.ncbi.nlm.nih.gov/25261040/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 250.0 600.28

Preparing Stock Solutions

The following data is based on the product molecular weight 416.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Cheung P, Zhang B, Puuvuori E, Estrada S, Amin MA, Ye S, Korsgren O, Odell LR, Eriksson J, Eriksson O. PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs. Biomedicines. 2021 Apr 16;9(4):434. doi: 10.3390/biomedicines9040434. PMID: 33923731; PMCID: PMC8073488. 2. Eriksson O. GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass. Curr Diab Rep. 2019 Jun 27;19(8):49. doi: 10.1007/s11892019-1164-z. PMID: 31250117; PMCID: PMC6597591. 3. Gil MA, Caniga M, Woodhouse JD, Eckman J, Lee HH, Salmon M, Naber J, Hamilton VT, Sevilla RS, Bettano K, Klappenbach J, Moy L, Correll CC, Gervais FG, Siliphaivanh P, Zhang W, Zhang-Hoover J, McLeod RL, Cicmil M. 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. doi: 10.1016/j.ejphar.2014.09.021. Epub 2014 Sep 23. PMID: 25261040.
In vitro protocol: 1. Cheung P, Zhang B, Puuvuori E, Estrada S, Amin MA, Ye S, Korsgren O, Odell LR, Eriksson J, Eriksson O. PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs. Biomedicines. 2021 Apr 16;9(4):434. doi: 10.3390/biomedicines9040434. PMID: 33923731; PMCID: PMC8073488. 2. Eriksson O. GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass. Curr Diab Rep. 2019 Jun 27;19(8):49. doi: 10.1007/s11892019-1164-z. PMID: 31250117; PMCID: PMC6597591.
In vivo protocol: 1. Gil MA, Caniga M, Woodhouse JD, Eckman J, Lee HH, Salmon M, Naber J, Hamilton VT, Sevilla RS, Bettano K, Klappenbach J, Moy L, Correll CC, Gervais FG, Siliphaivanh P, Zhang W, Zhang-Hoover J, McLeod RL, Cicmil M. 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. doi: 10.1016/j.ejphar.2014.09.021. Epub 2014 Sep 23. PMID: 25261040. 2. Cheung P, Zhang B, Puuvuori E, Estrada S, Amin MA, Ye S, Korsgren O, Odell LR, Eriksson J, Eriksson O. PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs. Biomedicines. 2021 Apr 16;9(4):434. doi: 10.3390/biomedicines9040434. PMID: 33923731; PMCID: PMC8073488.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Cheung P, Amin MA, Zhang B, Lechi F, Korsgren O, Eriksson J, Odell LR, Eriksson O. [18F]MK-7246 for Positron Emission Tomography Imaging of the Beta-Cell Surface Marker GPR44. Pharmaceutics. 2023 Feb 2;15(2):499. doi: 10.3390/pharmaceutics15020499. PMID: 36839820; PMCID: PMC9962486.


2: Cheung P, Zhang B, Puuvuori E, Estrada S, Amin MA, Ye S, Korsgren O, Odell LR, Eriksson J, Eriksson O. PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs. Biomedicines. 2021 Apr 16;9(4):434. doi: 10.3390/biomedicines9040434. PMID: 33923731; PMCID: PMC8073488.


3: Harish B , Yadav S , Suresh S . Design and application of intramolecular vinylogous Michael reaction for the construction of 2-alkenyl indoles. Chem Commun (Camb). 2021 Jan 7;57(2):231-234. doi: 10.1039/d0cc06564a. Epub 2020 Dec 10. PMID: 33300907.


4: Richards D, Gever JR, Ford AP, Fountain SJ. Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation. Br J Pharmacol. 2019 Jul;176(13):2279-2291. doi: 10.1111/bph.14677. Epub 2019 May 11. PMID: 30927255; PMCID: PMC6555852.


5: Eriksson O. GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass. Curr Diab Rep. 2019 Jun 27;19(8):49. doi: 10.1007/s11892-019-1164-z. PMID: 31250117; PMCID: PMC6597591.


6: Eriksson J, Roy T, Sawadjoon S, Bachmann K, Sköld C, Larhed M, Weis J, Selvaraju RK, Korsgren O, Eriksson O, Odell LR. Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass. Nucl Med Biol. 2019 Apr;71:1-10. doi: 10.1016/j.nucmedbio.2019.04.002. Epub 2019 Apr 13. PMID: 31082767.


7: Gil MA, Caniga M, Woodhouse JD, Eckman J, Lee HH, Salmon M, Naber J, Hamilton VT, Sevilla RS, Bettano K, Klappenbach J, Moy L, Correll CC, Gervais FG, Siliphaivanh P, Zhang W, Zhang-Hoover J, McLeod RL, Cicmil M. 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. doi: 10.1016/j.ejphar.2014.09.021. Epub 2014 Sep 23. PMID: 25261040.


8: Mauser PJ, House A, Jones H, Correll C, Boyce C, Chapman RW. Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats. Pulm Pharmacol Ther. 2013 Dec;26(6):677-84. doi: 10.1016/j.pupt.2013.03.005. Epub 2013 Mar 19. PMID: 23523662.


9: Wang YH, Trucksis M, McElwee JJ, Wong PH, Maciolek C, Thompson CD, Prueksaritanont T, Garrett GC, Declercq R, Vets E, Willson KJ, Smith RC, Klappenbach JA, Opiteck GJ, Tsou JA, Gibson C, Laethem T, Panorchan P, Iwamoto M, Shaw PM, Wagner JA, Harrelson JC. UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study. Clin Pharmacol Ther. 2012 Jul;92(1):96-102. doi: 10.1038/clpt.2012.20. Epub 2012 Jun 6. PMID: 22669291; PMCID: PMC3380185.


10: Molinaro C, Bulger PG, Lee EE, Kosjek B, Lau S, Gauvreau D, Howard ME, Wallace DJ, O'Shea PD. CRTH2 antagonist MK-7246: a synthetic evolution from discovery through development. J Org Chem. 2012 Mar 2;77(5):2299-309. doi: 10.1021/jo202620r. Epub 2012 Feb 15. PMID: 22335767.


11: Simard D, Leblanc Y, Berthelette C, Zaghdane MH, Molinaro C, Wang Z, Gallant M, Lau S, Thao T, Hamel M, Stocco R, Sawyer N, Sillaots S, Gervais F, Houle R, Lévesque JF. Azaindoles as potent CRTH2 receptor antagonists. Bioorg Med Chem Lett. 2011 Jan 15;21(2):841-5. doi: 10.1016/j.bmcl.2010.11.084. Epub 2010 Nov 21. PMID: 21185722.


12: Gallant M, Beaulieu C, Berthelette C, Colucci J, Crackower MA, Dalton C, Denis D, Ducharme Y, Friesen RW, Guay D, Gervais FG, Hamel M, Houle R, Krawczyk CM, Kosjek B, Lau S, Leblanc Y, Lee EE, Levesque JF, Mellon C, Molinaro C, Mullet W, O'Neill GP, O'Shea P, Sawyer N, Sillaots S, Simard D, Slipetz D, Stocco R, Sørensen D, Truong VL, Wong E, Wu J, Zaghdane H, Wang Z. Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases. Bioorg Med Chem Lett. 2011 Jan 1;21(1):288-93. doi: 10.1016/j.bmcl.2010.11.015. Epub 2010 Nov 5. PMID: 21106375.


13: Gervais FG, Sawyer N, Stocco R, Hamel M, Krawczyk C, Sillaots S, Denis D, Wong E, Wang Z, Gallant M, Abraham WM, Slipetz D, Crackower MA, O'Neill GP. 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. doi: 10.1124/mol.110.068585. Epub 2010 Oct 13. PMID: 20943773.