MK-7246 is a potent and selectiveCRTH2antagonist with aK_iof 2.5±0.5 nM.

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 [³H]PGD₂specific 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 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)^[1].

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 inA. alternatachallenged Brown Norway rats (n=8 per group). Mast cell derived production of Prostaglandin D₂(PGD₂) 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 onA. alternateelicited pulmonary inflammatory responses. CRTH2 inhibitor MK-7246 is orally administered 1 h before and 23 h post-intratracheal instillation of theA. 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].

416.47

Solid

C₂₁H₂₁FN₂O₄S

1218918-62-7

Room temperature in continental US; may vary elsewhere.

DMSO : 300 mg/mL(720.34 mM;ultrasonic and warming and heat to 60℃)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: 3.75 mg/mL (9.00 mM); Suspended solution; Need ultrasonic

  此方案可获得 3.75 mg/mL (9.00 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 37.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: 3.75 mg/mL (9.00 mM); Suspended solution; Need ultrasonic

  此方案可获得 3.75 mg/mL (9.00 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 37.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: 3.75 mg/mL (9.00 mM); Clear solution; Need ultrasonic

  此方案可获得 3.75 mg/mL (9.00 mM) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 37.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。