S18-000003
Based on 1 Customer Validation
S18-000003 is a potent, selective and orally active inhibitor of retinoic acid receptor-related orphan receptor-gamma-t (RORγt), with an IC50 of <30 nM towards human RORγt in competitive binding assays. S18-000003 shows selectivity for RORγt over other ROR family members (IC50>10 μM). S18-000003 can be used for the research of psoriasis with low risk of thymic aberrations.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.42%
- No. CAS: 2068119-11-7
- Fòrmula: C26H25F3N2O4S
- Peso molecular:518.55
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Almacenamiento:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
RORγt <30 nM (IC50) |
In Vitro
S18-000003 inhibits human and mouse RORγt-dependent transactivation, with IC50s of 0.029 and 0.34 μM respectively in cell-based GAL4 promoter reporter assays[1].
S18-000003 (0.003-0.3 μM; 7 d) dose-dependently inhibits Th17 cell differentiation from human naive CD4+T cells, with an IC50 of 0.024 μM[2].
S18-000003 (0.1-3 μM; 4 d) inhibits the differentiation of mouse Th17 cells from splenic naive CD4+T cells, with an IC50 of 0.20 μM[2].
S18-000003 (0.03-1 μM; 3 d) reduces the IL-17 production in human PBMCs in a dose-dependent manner, and does not inhibit either the production of other cytokines (IL-2, IL-4, IL-10 and IFN-g) or cell proliferation[2].
S18-000003 (0.1-3 μM; 3 d) reduces IL-17 and IL-22 production in PBMCs from psoriatic mice in a dose-dependent manner[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
S18-000003 (0.1-8%; 100mL; topically administration once daily for 14 days) ameliorates psoriasis-like lesions in TPA-induced K14.Stat3C transgenic mice, and has little impact on the thymus[2].
S18-000003 (0.5 mg/kg; i.v.) exhibits the half-life (3.2 h), AUC (1930 ng h/mL), CLtot (4.33 mL/min/kg) and Vdss in rats[1].
S18-000003 (1 mg/kg; p.o.) exhibits the oral bioavailability (54.5%), Cmax (185 ng/mL), AUC (2110 ng h/mL) and Tmax (4 h) in rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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No. CAS 2068119-11-7
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Appearance Solid
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Peso molecular 518.55
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Fòrmula C26H25F3N2O4S
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Color White to yellow
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SMILES
FC1=C(NC(C(C)(C)C2=CC=C(NC(CC3=CC=C(S(CC)(=O)=O)C=C3)=O)C=C2F)=O)C=CC(F)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (192.85 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (4.82 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.82 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (273 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Sasaki Y, et, al. Discovery of a potent orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitor, S18-000003. Bioorg Med Chem Lett. 2018 Dec 1;28(22):3549-3553. [Content Brief]
[2]. Imura C, et, al. A novel RORγt inhibitor is a potential therapeutic agent for the topical treatment of psoriasis with low risk of thymic aberrations. J Dermatol Sci. 2019 Mar;93(3):176-185. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9285 mL | 9.6423 mL | 19.2845 mL | 48.2114 mL |
| 5 mM | 0.3857 mL | 1.9285 mL | 3.8569 mL | 9.6423 mL | |
| 10 mM | 0.1928 mL | 0.9642 mL | 1.9285 mL | 4.8211 mL | |
| 15 mM | 0.1286 mL | 0.6428 mL | 1.2856 mL | 3.2141 mL | |
| 20 mM | 0.0964 mL | 0.4821 mL | 0.9642 mL | 2.4106 mL | |
| 25 mM | 0.0771 mL | 0.3857 mL | 0.7714 mL | 1.9285 mL | |
| 30 mM | 0.0643 mL | 0.3214 mL | 0.6428 mL | 1.6070 mL | |
| 40 mM | 0.0482 mL | 0.2411 mL | 0.4821 mL | 1.2053 mL | |
| 50 mM | 0.0386 mL | 0.1928 mL | 0.3857 mL | 0.9642 mL | |
| 60 mM | 0.0321 mL | 0.1607 mL | 0.3214 mL | 0.8035 mL | |
| 80 mM | 0.0241 mL | 0.1205 mL | 0.2411 mL | 0.6026 mL | |
| 100 mM | 0.0193 mL | 0.0964 mL | 0.1928 mL | 0.4821 mL |
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