Setipiprant
(Synonyms: 司替匹仑,ACT-129968; KYTH-105) 目录号 : GC19327
Setipiprant是一种选择性、口服可用的前列腺素 D2 受体 2（DP2，也称为 CRTH2）拮抗剂，是γ-咔啉衍生物，其IC₅₀为6nM。
Cas No.:866460-33-5
Sample solution is provided at 25 µL, 10mM.
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Setipiprant is a selective and orally available prostaglandin D2 receptor 2 (DP2, also known as CRTH2) antagonist, which is a γ-carboline derivative with an IC₅₀ of 6nM[1]. As a G protein-coupled receptor, the DP2 receptor is mainly expressed on the surface of immune cells such as eosinophils and Th2 cells, and is involved in regulating allergic inflammatory responses, immune cell migration, and cytokine release[2]. By specifically blocking the DP2 receptor, Setipiprant has shown significant anti-inflammatory effects in models of inflammatory diseases such as allergic asthma and atopic dermatitis[3].
In vitro, when hESC cells are treated with Setipiprant (1-10μM) for 10 minutes, the compound inhibits PGD₂-induced eosinophil activation and shape change by blocking the CRTH2 receptor[1].
In vivo, after intravenous injection of Setipiprant (2mg/kg) in rats and dogs, relevant bioavailability data indicate that the compound exhibits good oral bioavailability and excellent pharmacokinetic properties in both animal species[1]. In addition, Setipiprant (1%) can effectively inhibit the activities of rat lens aldose reductase and kidney aldose reductase[4].
References:
[1] Fretz H, Valdenaire A, Pothier J, et al. Identification of 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968), a Potent, Selective, and Orally Bioavailable Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) Antagonist. Journal of Medicinal Chemistry 2013, 56(12):4899-4911.
[2] Kupczyk M, Kuna P Targeting the PGD2/CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives. Drugs 2017, 77(12):1281-1294.
[3] Strasser DS, Farine H, Holdener M, et al. Development of a decision-making biomarker for CRTH2 antagonism in clinical studies. New Horizons in Translational Medicine 2015, 2(4):118-125.
[4] Ballekova J, Soltesova-Prnova M, Majekova M, et al. Does inhibition of aldose reductase contribute to the anti-inflammatory action of setipiprant? Physiol Res 2017, 66(4):687-693.
Setipiprant是一种选择性、口服可用的前列腺素D2受体2（DP2，也称为CRTH2）拮抗剂，是γ-咔啉衍生物，其IC₅₀为6nM[1]。DP2受体作为一种G蛋白偶联受体，主要表达于嗜酸性粒细胞、Th2细胞等免疫细胞表面，参与调控过敏性炎症反应、免疫细胞迁移及细胞因子释放等过程[2]。Setipiprant通过特异性阻断DP2受体，在过敏性哮喘、特应性皮炎等炎症性疾病模型中显示出显著的抗炎功效[3]。
在体外，使用Setipiprant（1-10μM）处理hESC细胞10分钟，该化合物通过阻断CRTh2 受体，抑制PGD₂诱导的嗜酸性粒细胞活化及形状改变[1]。
在体内，使用Setipiprant（2mg/kg）对大鼠和犬进行静脉注射后，相关生物利用度数据表明，该化合物在这两种动物中均展现出良好的口服生物利用度及优异的药代动力学特性[1]。此外，Setipiprant（1%）能有效抑制大鼠晶状体醛糖还原酶和肾脏醛糖还原酶活性[4]。
| Cell experiment [1]: | |
Cell lines | hESC |
Preparation Method | Whole blood was collected from healthy volunteers. Polymorphonuclear leukocytes (PMNs) were isolated by Polymorphprep density gradient centrifugation (500g, 30min). After hypotonic lysis to remove red blood cells, a cell suspension containing eosinophils was obtained. Resuspend PMNs in PBS buffer containing Ca²⁺/Mg²⁺ (supplemented with 0.1%BSA, 10mM Hepes, 10mM glucose, pH7.4), adjust the concentration to 1×10⁶ cells/mL, and tag eosinophils with CD49d-APC antibody Incubation at room temperature for 1hour. Mix 45μL of human plasma, 10μL of detection buffer with 30μL of PMNs (1.3×10⁷cells/mL), add different concentrations of Setipiprant and pre-incubate for 10 minutes, then add 15nMPGD₂ to activate the cells and incubate at 37°C for 5 minutes. The FACSAria flow cytometer was used to gate eosinophils by CD49d-APC fluorescence signal and lateral scattering (SSC), and to detect the changes in forward scattering (FSC)-an increase in FSC reflects changes in cell shape (such as degranulation, polarization). |
Reaction Conditions | 1-10μM; 10 min |
Applications | Setipiprant inhibits eosinophil activation and shape changes induced by PGD₂. |
| Animal experiment [1]: | |
Animal models | Male Wistar rats |
Preparation Method | Plasma samples of rats were collected at different time points after administration. The efficacy was evaluated by measuring the pharmacokinetic parameters in plasma, including AUC0-last (area under the drug-time curve), CL (plasma clearance rate), T₁/₂ (half-life), and F (oral bioavailability), etc. These parameters were obtained by analyzing plasma samples collected at different time points after administration in rats, and ultimately the pharmacokinetic characteristics of Setipiprant in rats were determined. Among them, the oral bioavailability was 44%, and the plasma exposure (AUC0-last) was 58,500ng·h/mL. The plasma clearance rate was 1.3mL·min⁻¹·kg⁻¹, and the half-life was 6 hours. |
Dosage form | 2mg/kg |
Applications | Setipiprant can effectively inhibit aldose reductase in the lens and kidneys of rats. |
References: | |
| Cas No. | 866460-33-5 | SDF | |
| 别名 | 司替匹仑,ACT-129968; KYTH-105 | ||
| Canonical SMILES | O=C(O)CN1C2=C(CN(C(C3=C4C=CC=CC4=CC=C3)=O)CC2)C5=C1C=CC(F)=C5 | ||
| 分子式 | C24H19FN2O3 | 分子量 | 402.42 |
| 溶解度 | DMSO : ≥ 36 mg/mL (89.46 mM) | 储存条件 | Store at RT |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.485 mL | 12.4248 mL | 24.8497 mL |
| 5 mM | 0.497 mL | 2.485 mL | 4.9699 mL |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.485 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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