| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
RORγt 51 nM (IC50)
RORγt Inverse agonist 10 targets the retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt). As an inverse agonist, it binds to RORγt and suppresses its transcriptional activity. RORγt is a major transcription factor for genes such as IL-17A, IL-22, and IL-23R, which are involved in the pathogenesis of psoriasis. By inhibiting RORγt, the compound has potential applications in treating psoriasis and other Th17-driven autoimmune diseases. |
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| ln Vitro |
The liver microsome stability of RORγt Inverse Antagonist 10 is good (human CLint=0.010 mL/min/mg, mouse CLint=0.030 mL/min/mg)[1]. In a test using human whole blood, RORγt Inverse Antagonist 10 inhibits the synthesis of IL-17A in a dose-dependent manner, with an IC50 of 130 nM[1].
In vitro, RORγt Inverse agonist 10 demonstrates potent activity with an IC₅₀ of 51 nM. This value indicates its high potency in inhibiting RORγt-mediated transcriptional activity. The compound is used in cell-based assays to investigate its effects on RORγt signaling and Th17 cell differentiation. Its potency makes it suitable for studying psoriasis pathogenesis and other Th17-driven autoimmune diseases. The compound is supplied for research purposes only. |
| ln Vivo |
In the mouse IL-18/23-induced cytokine expression paradigm, RORγt Inverse Antagonist 10 (3-100 mg/kg; po) exhibits a strong and dose-dependent inhibitory effect on the production of IL-17A[1]. The inverse agonist RORγt 10 (1.145 mg/kg; po) has a 3.6-hour t1/2 and a high AUC of 15000 nM*h[1].
In vivo, RORγt Inverse agonist 10 is orally bioavailable, indicating that it can be administered orally and maintain its biological activity. It is used in preclinical studies to investigate its effects on Th17-driven inflammatory responses. Dosing ranges of 3-100 mg/kg are reported. Its oral bioavailability and potency make it suitable for in vivo efficacy studies in animal models of psoriasis. Specific efficacy data are not detailed in the available sources. |
| Enzyme Assay |
Non-cell-based enzyme/receptor binding assays for RORγt Inverse agonist 10 typically involve competitive binding studies using purified RORγt protein. Standard protocols include incubating varying concentrations of the test compound with the RORγt ligand-binding domain and a radiolabeled or fluorescent probe in appropriate buffer systems, followed by separation of bound from free ligand via filtration or fluorescence polarization. Binding affinity (IC₅₀ values) is calculated using nonlinear regression analysis. The compound shows an IC₅₀ of 51 nM. Surface plasmon resonance (SPR) may also be employed.
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| Cell Assay |
Cell-based assays for RORγt Inverse agonist 10 typically utilize reporter gene assays with cells expressing RORγt and a luciferase reporter, or Th17 cell differentiation assays. Standard protocols involve culturing cells in appropriate media at 37°C in 5% CO₂, followed by treatment with varying concentrations of the compound (typically 0.01-10 μM) for 18-24 hours. Reporter gene activity is quantified by luminescence. IL-17 production is measured by ELISA. IC₅₀ values are calculated from dose-response curves. The compound shows an IC₅₀ of 51 nM.
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| Animal Protocol |
Animal/Disease Models: C57/BL6 male mice, mouse IL-18/23-induced cytokine expression model[1]
Doses: 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg Route of Administration: Oral administration Experimental Results: Dramatically inhibited the IL-17A production in a dose-dependent manner. Animal/Disease Models: Mice[1] Doses: 1.145 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Oral administration Experimental Results: AUC=15000 nM*h, t1/2=3.6 hrs (hours). In vivo animal studies for RORγt Inverse agonist 10 typically involve oral administration in rodent models (mice or rats) of psoriasis or other Th17-driven autoimmune diseases. Standard protocols include dosing at ranges of 3-100 mg/kg body weight, with observations over 7-14 days depending on the study objectives. Efficacy is assessed by measuring skin inflammation scores, cytokine levels, and histological analysis. Pharmacodynamic assessments may include blood sampling for compound exposure analysis and cytokine profiling. All animal studies must comply with institutional ethical guidelines. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties for RORγt Inverse agonist 10 are characterized by oral bioavailability. The compound has a molecular weight of 572.50 g/mol. For in vivo administration, formulations using suitable co-solvent systems may be employed. The compound should be stored at 4°C, away from moisture and light. Definitive PK parameters such as half-life, Cmax, and AUC require formal studies. The compound is supplied for research purposes only.
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| References | |
| Additional Infomation |
RORγt Inverse agonist 10 is a potent and orally bioavailable RORγt inverse agonist with an IC₅₀ of 51 nM. RORγt is a major transcription factor for genes related to psoriasis pathogenesis such as IL-17A, IL-22, and IL-23R. The compound is used in research to study psoriasis and other Th17-driven autoimmune diseases. It is not an approved drug and has not undergone clinical trials; it is strictly for research purposes.
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| Molecular Formula |
C25H26F6N6O3
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|---|---|
| Molecular Weight |
572.50
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| Exact Mass |
572.197
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| CAS # |
2413986-35-1
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| PubChem CID |
146673074
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
40
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| Complexity |
893
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C(F)(F)(C(CC(N1[C@@H](C)C[C@@H](OC2C3=NC=NN3C=C(NC(=O)C3C=CC(C)=NC=3)C=2C)CC1)=O)C(F)(F)F)F
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| InChi Key |
FUKNWBDJYWPXRK-YOEHRIQHSA-N
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| InChi Code |
InChI=1S/C25H26F6N6O3/c1-13-4-5-16(10-32-13)23(39)35-18-11-37-22(33-12-34-37)21(15(18)3)40-17-6-7-36(14(2)8-17)20(38)9-19(24(26,27)28)25(29,30)31/h4-5,10-12,14,17,19H,6-9H2,1-3H3,(H,35,39)/t14-,17-/m0/s1
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| Chemical Name |
6-methyl-N-[7-methyl-8-[(2S,4S)-2-methyl-1-[4,4,4-trifluoro-3-(trifluoromethyl)butanoyl]piperidin-4-yl]oxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl]pyridine-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (174.67 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 10 mg/mL (17.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 100.0 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: ≥ 10 mg/mL (17.47 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 100.0 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: ≥ 10 mg/mL (17.47 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 | 1.7467 mL | 8.7336 mL | 17.4672 mL | |
| 5 mM | 0.3493 mL | 1.7467 mL | 3.4934 mL | |
| 10 mM | 0.1747 mL | 0.8734 mL | 1.7467 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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