| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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S18-000003 is a novel, potent and orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitor with the potential to be used for psoriasis with low risk of thymic aberrations. It inhibits RORγt with an IC50 of 29 nM, also inhibits IL-17 production.
| ln Vitro |
In a cell-based GAL4 promoter reporter gene experiment, S18-000003 suppresses RORγt-dependent transactivation in both humans and mice, with IC50 values of 0.029 and 0.34 μM, respectively [1]. With an IC50 of 0.024 μM, S18-000003 (0.003-0.3 μM; 7 d) dose-dependently prevents human naive CD4+ T cell development into Th17 cells[2]. With an IC50 of 0.20 μM, S18-000003 (0.1-3 μM; 4 d) prevents mouse Th17 cells from differentiating from spleen naive CD4+ T cells [2]. S18-000003 (0.03-1 μM; 3 d) did not affect cell proliferation or other cytokines (IL-2, IL-4, IL-10, and IFN-g) but does decrease IL-17 production in human PBMC in a dose-dependent manner[2]. In PBMC of psoriatic mice, S18-000003 (0.1-3 μM; 3d) decreases IL-17 and IL-22 production in a dose-dependent manner [2].
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| ln Vivo |
S18-000003 (30-100 mg/kg; oral) dose-dependently suppresses the production of IL-17 in the skin of mice treated with IL-23 [1]. In K14.Stat3C transgenic mice, TPA-induced psoriasis-like lesions are improved by S18-000003 (0.1-8%; 100mL; topically applied once daily for 14 days) with little effect on the thymus [2]. Rats were used to test the half-life (3.2 h), AUC (1930 ng·h/mL), CLtot (4.33 mL/min/kg), and Vdss of S18-000003 (0.5 mg/kg; iv) [1]. In rats, oral bioavailability (54.5%), Cmax (185 ng/mL), AUC (2110 ng·h/mL), and Tmax (4 h) were demonstrated by S18-000003 (1 mg/kg; po) [ 1].
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| References |
[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.
[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. |
| Molecular Formula |
C26H25F3N2O4S
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|---|---|
| Molecular Weight |
518.5512
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| Exact Mass |
518.1487
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| CAS # |
2068119-11-7
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| Related CAS # |
2068119-11-7;
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| SMILES |
S(CC)(C1C=CC(=CC=1)CC(NC1C=CC(=C(C=1)F)C(C(NC1C=CC(=CC=1F)F)=O)(C)C)=O)(=O)=O
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| Synonyms |
S-18-000003 S 18-000003 S18-000003
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~192.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.82 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9285 mL | 9.6423 mL | 19.2845 mL | |
| 5 mM | 0.3857 mL | 1.9285 mL | 3.8569 mL | |
| 10 mM | 0.1928 mL | 0.9642 mL | 1.9285 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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