| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ROR-γ 63.8 nM (IC50)
RORγt inverse agonist 13 targets the retinoic acid receptor-related orphan receptor gamma t (RORγt), a nuclear receptor transcription factor critical for Th17 cell differentiation. 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 and other autoimmune diseases. The compound exhibits improved drug-like properties. |
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| ln Vitro |
In the Th17 cell differentiation experiment, RORγt inverse agonist 13 (Compound 3i) shows action with an inhibition of 76% at 0.3 µM[1].
In vitro, RORγt inverse agonist 13 demonstrates potent activity with an IC₅₀ of 63.8 nM. It shows 76% inhibition at 0.3 μM in Th17 cell differentiation assays. These data indicate its potency in inhibiting RORγt-mediated Th17 cell differentiation. The compound is selective for RORγt. Its improved drug-like properties make it suitable for cell-based assays investigating Th17-driven autoimmune diseases. The compound is used for studying RORγt inverse agonism. |
| ln Vivo |
In an IMQ-induced psoriasis mouse model, RORγt inverse agonist 13 (Compound 3i, 25 mg/kg, Orally, twice daily) has good in vivo effectiveness and an outstanding in vivo PK profile[1].
In vivo, RORγt inverse agonist 13 (25 mg/kg, orally, twice daily) demonstrates an excellent PK profile and good efficacy in an IMQ-induced psoriasis mouse model. These data demonstrate its in vivo efficacy in modulating Th17-driven inflammatory responses in a disease-relevant model. The compound's oral activity and good efficacy support its potential for treating psoriasis and other Th17-driven autoimmune diseases. Its excellent PK profile indicates favorable drug-like properties. |
| Enzyme Assay |
Non-cell-based enzyme/receptor binding assays for RORγt inverse agonist 13 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 63.8 nM. Surface plasmon resonance (SPR) may also be employed.
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| Cell Assay |
Cell-based assays for RORγt inverse agonist 13 typically utilize Th17 cell differentiation assays or reporter gene assays with cells expressing RORγt and a luciferase reporter. 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 3-5 days. Th17 cell differentiation is assessed by measuring IL-17 production via ELISA. Reporter gene activity is quantified by luminescence. The compound shows 76% inhibition at 0.3 μM in Th17 cell differentiation assays.
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| Animal Protocol |
Animal/Disease Models: Imiquimod (IMQ) -induced psoriasis mice model[1].
Doses: 25 mg/kg. Route of Administration: Orally, twice (two times) daily. Experimental Results: Brought in a significant reduction in clinical severity of psoriasis as measured through the ear erythema, back skin erythema and scaliness scales. Animal/Disease Models: Male CD-1 Mice[1]. Doses: 1 mg/kg (iv) and 5 mg/kg (po)(pharmacokinetic/PK Analysis). Route of Administration: IV or PO, single dose. Experimental Results: Cmax: 609.67 ng/mL (PO), 1550 ng/mL (IV). T1/2: 3.63 h (PO), 3.04 h (IV). In vivo animal studies for RORγt inverse agonist 13 typically involve the IMQ-induced psoriasis mouse model. Standard protocols include oral administration at 25 mg/kg twice daily. Efficacy is assessed by measuring skin inflammation scores, epidermal thickness, and IL-17A levels. Pharmacodynamic assessments may include blood sampling for compound exposure analysis and cytokine profiling. The compound demonstrates good efficacy in this model. All animal studies must comply with institutional ethical guidelines. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties for RORγt inverse agonist 13 are characterized by oral bioavailability and an excellent PK profile. The compound has a molecular weight of 513.29 g/mol and shows solubility in DMSO (10 mg/mL). For in vivo administration, formulations using 10% DMSO + 90% Corn Oil (1 mg/mL) are recommended. The compound should be stored as powder at -20°C for up to 3 years or in solvent at -80°C for 1 year. Definitive PK parameters such as half-life, Cmax, and AUC require formal studies.
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| References | |
| Additional Infomation |
RORγt inverse agonist 13 (Compound 3i) is a potent, orally active, and selective inverse agonist for RORγt with an IC₅₀ of 63.8 nM. It demonstrates good efficacy in an IMQ-induced psoriasis mouse model and exhibits improved drug-like properties. The compound is used for studying 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 |
C23H17CL2F3N2O4
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|---|---|
| Molecular Weight |
513.2933
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| Exact Mass |
512.051
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| CAS # |
2170477-75-3
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| PubChem CID |
138583953
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| Appearance |
White to off-white solid powder
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| LogP |
5.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
680
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C(C([H])=C(C=1C1=C([H])C([H])=C([H])C([H])=C1OC(F)(F)F)Cl)N([H])C(N([H])C([H])([H])C1C([H])=C([H])C(C([H])([H])C(=O)O[H])=C([H])C=1[H])=O
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| InChi Key |
ZBAVYJYWRYFFEJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H17Cl2F3N2O4/c24-17-10-15(30-22(33)29-12-14-7-5-13(6-8-14)9-20(31)32)11-18(25)21(17)16-3-1-2-4-19(16)34-23(26,27)28/h1-8,10-11H,9,12H2,(H,31,32)(H2,29,30,33)
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| Chemical Name |
2-[4-[[[3,5-dichloro-4-[2-(trifluoromethoxy)phenyl]phenyl]carbamoylamino]methyl]phenyl]acetic acid
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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 |
| 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 (194.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9482 mL | 9.7411 mL | 19.4822 mL | |
| 5 mM | 0.3896 mL | 1.9482 mL | 3.8964 mL | |
| 10 mM | 0.1948 mL | 0.9741 mL | 1.9482 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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