Ramatroban is a selective thromboxane A₂ (TxA₂, IC₅₀=14 nM) antagonist, which also antagonizes CRTH2 (IC₅₀=113 nM) by inhibiting PGD₂ binding.

Ramatroban is a potent human thromboxane receptor (hTP) antagonist with an IC₅₀ of 18 nM in a human TP binding assay. Ramatroban inhibits prostaglandin D₂ receptor DP2 (CRTH2) with an IC₅₀ of 113 nM in a human DP2 binding assay. Ramatroban also inhibits human CYP isoform CYP2C9 with an IC₅₀ of 15 μM^[1]. Ramatroban is a selective thromboxane-type prostanoid (TP) receptor antagonist. PGD₂-stimulated human eosinophil migration is shown to be mediated exclusively through activation of CRTH2, and surprisingly, these effects are completely inhibited by Ramatroban. Ramatroban is an antagonist for CRTH2, and inhibits PGD₂-induced migration of eosinophils via CRTH2 blockade. ³H-labeled PGD₂ binds to a single site on CRTH2 transfectants with high affinity (K_D=6.3 nM, B_max=450 pM). Nonlabeled PGD₂ inhibits the binding of ³H-labeled PGD₂ to CRTH2 transfectants in a concentration-dependent manner with an EC₅₀ value of 2.7 nM. Ramatroban shows significant inhibitory effects on the binding of ³H-labeled PGD₂ to CRTH2, albeit with much lower potency (IC₅₀=100 nM). Ramatroban also inhibits PGD₂-induced Ca²⁺ mobilization in CRTH2 transfectants to almost the same extent with an IC₅₀ value of 30 nM. Ramatroban completely inhibits the PGD₂-induced migration of eosinophils in a concentration-dependent manner with an IC₅₀ value of 170 nM^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Ramatroban is an orally bioavailable small molecule antagonist of CRTH2. Systemic administration of Ramatroban (30 mg/kg) in CRTH2^+/+ mice produces the same effects as seen in CRTH2 deficiency. Ramatroban completely blocks LPS-induced decreases in social and object exploratory behavior (p<0.01). In addition, tumor-impaired social interaction and object exploratory behavior in CRTH2^+/+ mice are completely reversed by a single injection of Ramatroban, even when the tumor is enlarged^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

416.47

C₂₁H₂₁FN₂O₄S

116649-85-5

雷马曲班

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (300.14 mM; Need ultrasonic)

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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: ≥ 2.08 mg/mL (4.99 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.99 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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-CD in saline)

  Solubility: ≥ 2.08 mg/mL (4.99 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.99 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 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: ≥ 2.08 mg/mL (4.99 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.99 mM，饱和度未知) 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Stearns BA, et al. Novel tricyclic antagonists of the prostaglandin D₂ receptor DP2 with efficacy in a murine modelof allergic rhinitis. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4647-51.

  [2]. Sugimoto H, et al. An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D₂-induced eosinophil migration in vitro. J Pharmacol Exp Ther. 2003 Apr;305(1):347-52.

  [3]. Haba R, et al. Central CRTH2, a second prostaglandin D₂ receptor, mediates emotional impairment in the lipopolysaccharide and tumor-induced sickness behavior model. J Neurosci. 2014 Feb 12;34(7):2514-23.

CRTH2 transfectants are resuspended in binding buffer (50 mM Tris-HCl, pH 7.4, 40 mM MgCl₂, 0.1% BSA, 0.1% NaN₃). Cell suspension (2×10⁵ cells), ³H-labeled PGD₂, and various concentrations of Ramatroban (0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM and 10 μM) are then mixed in a 96-well U-bottomed polypropylene plate and incubated in a final volume of 100 μL for 60 min at room temperature. After incubation, the cell suspension is transferred to a filtration plate and washed three times with binding buffer. Scintillant is added to the filtration plate, and radioactivity remaining on the filter is measured by a scintillation counter. Nonspecific binding is determined by incubating the cell suspension and ³H-labeled PGD₂ in the presence of 1 μM unlabeled PGD₂^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Human eosinophils are purified and resuspended in migration buffer (20 mM HEPES, pH 7.6, 0.1% BSA, Hanks’ solution) at a density of 6 ×10⁶ cells/mL. Fifty microliters of the cell suspension (3×10⁵ cells/well) is then dispensed into the upper chamber of a 96-well type chemotaxis chamber (pore diameter=5 μm), and 30 μL of ligand solution is added to the lower chamber. Cells are preincubated with various concentrations of Ramatroban (0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM and 10 μM) or BWA868C at 37°C for 10 min. The migration assays are performed in a humidified incubator at 37°C, 5% CO₂ for 2 h. The number of cells migrating into the lower chamber is counted^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[3]
Five micrograms of LPS (closed columns) or saline (open columns) are intraperitoneally injected into CRTH2^+/+ mice. CRTH2^+/+ mice are pretreated intraperitoneally for 1 h with 30 mg/kg Ramatroban.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Stearns BA, et al. Novel tricyclic antagonists of the prostaglandin D₂ receptor DP2 with efficacy in a murine modelof allergic rhinitis. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4647-51.

  [2]. Sugimoto H, et al. An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D₂-induced eosinophil migration in vitro. J Pharmacol Exp Ther. 2003 Apr;305(1):347-52.

  [3]. Haba R, et al. Central CRTH2, a second prostaglandin D₂ receptor, mediates emotional impairment in the lipopolysaccharide and tumor-induced sickness behavior model. J Neurosci. 2014 Feb 12;34(7):2514-23.