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CAS No.: 1218918-62-7

MK-7246 Catalog No. CSN24302

MK-7246 is a potent and selective CRTH2 antagonist with Ki value of 2.5nM.

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生物活性

实验方案

技术信息

生物活性

描述The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is a G protein-coupled receptor that has been reported to modulate inflammatory responses in various rodent models of asthma, allergic rhinitis and atopic dermatitis^[3]. MK-7246 is a potent and selective CRTH2 antagonist with a K_i of 2.5 ± 0.5 nM^[3]. 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 EP₂, 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, IC₅₀ = 33.2 μM) and MAPK3 (ERK1, IC₅₀ = 49.4 μM)^[3]. MK-7246 yields ex vivo blockade of CRTH2 on eosinophils in monkeys and sheep, and it significantly blocks antigen-induced late-phase bronchoconstriction and airway hyper-responsiveness in sheep^[3]. In a dose-dependent manner, MK-7246 decreased eosinophil influx and Th2 cytokine production following the alternaria alternata challenge^[4].

动物研究

剂量

Rat: 1 mg/kg^[1] (i.v.) Pig: 1 mg/kg^[2] (i.v.)

给药途径

i.v.

动物药代数据

Animal	Rats^[1]	Dogs^[1]	Monkeys^[1]
Dose	10 mg/kg (p.o.) 5 mg/kg (i.v.)	1 mg/kg (p.o.) 0.5 mg/kg (i.v.)	1 mg/kg (p.o., rhesus) 0.5 mg/kg (i.v., rhesus)
Administration	p.o. i.v.	p.o. i.v.	p.o. i.v.
F	1.07	0.67	0.57
T_1/2	5.6 h	8.4 h	8.1 h
CL	2.2 ml/min/kg	15 ml/min/kg	6.9 ml/min/kg
Vd_ss	0.98 L/kg	2.3 L/kg	2.6 L/kg

参考文献

[1] Gallant M, Beaulieu C, et al. 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.
[2] Eriksson J, Roy T, et al. 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.
[3] 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.
[4] 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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.4012 mL
- 12.0058 mL
- 24.0116 mL
- 5 mM
- 0.4802 mL
- 2.4012 mL
- 4.8023 mL
- 10 mM
- 0.2401 mL
- 1.2006 mL
- 2.4012 mL

技术信息

CAS号

1218918-62-7

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C21H21FN2O4S

运输

蓝冰

分子量

416.47

别名

溶解度

DMSO	250.0 mg/mL (600.3 mM)

动物实验配方

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