Setipiprant (Synonyms: ACT-129968) |
Catalog No.GC19327
One-Click Copy Product Info
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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.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Synonyms | ACT-129968 | ||
| Canonical SMILES | O=C(O)CN1C2=C(CN(C(C3=C4C=CC=CC4=CC=C3)=O)CC2)C5=C1C=CC(F)=C5 | ||
| Formula | C24H19FN2O3 | M.Wt | 402.42 |
| Solubility | DMSO : ≥ 36 mg/mL (89.46 mM) | Storage | Store at RT |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.485 mL | 12.4248 mL | 24.8497 mL |
| 5 mM | 497 μL | 2.485 mL | 4.9699 mL |
| 10 mM | 248.5 μL | 1.2425 mL | 2.485 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 27 reference(s) in Google Scholar.)