RORγt inverse agonist 29 is a novel and oral RORγt inverse agonist (IC50: 21 nM) with the potential to be used in skin inflammation and autoimmune diseases like psoriasis.
Physicochemical Properties
| Molecular Formula | C25H24N2O5S |
| Molecular Weight | 464.53 |
| Appearance | Typically exists as solid at room temperature |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | In human Jurkat cells, RORγt inverse agonist 29 (compound b12) exhibits strong RORγt transcriptional inhibitory action (IC50: 28 nM)[1]. In vitro human liver microsomes, RORγt inverse agonist 29 (10 μM) exhibits good metabolic stabilities, with comparable half-lives (T1/2: 4.46 h) and HLM (CLint(liver): 4.8 mL/min/kg)[1]. |
| ln Vivo | In a mouse model of Imiquimod-induced skin inflammation, RORγt inverse agonist 29 (po, 100 mg/kg) decreases the development of clinical symptoms and the total Psoriasis Area[1]. In rats, RORγt inverse agonist 29 (iv, po, 0.3 or 1 mg/kg) has a half-life and a satisfactory bioavailability[1]. |
| Animal Protocol |
Animal/Disease Models: Mouse Imiquimod-induced skin inflammation model[1] Doses: 15 mg/kg, 50 mg/kg, 100 mg/kg Route of Administration: Oral administration, twice a day for 13 days. Experimental Results: Inhibited IL-6 and IL-17A protein in the serum, with inhibition rate of 58.06% (IL-6) and 84.07% (IL-17A) at 100 mg/kg. decreased the histopathological symptoms on the back skin at dose of 100 mg/kg. Alleviated symptoms including mononuclear and inflammatory cell infiltration, skin layer thickening, and dermal telangiectasia. Animal/Disease Models: Rats (pharmacokinetic/PK assay)[1] Doses: 0.3 mg/kg (iv) , 1 mg/kg (po) Route of Administration: intravenous (iv) injection, oral administration Experimental Results: pharmacokinetic/PK profile of RORγt inverse agonist 29 (compound b12). administration route T1/2 (h) Tmax (h) Cmax (ng/mL) AUC0-t (ng·h/mL) AUC0-∞ (ng·h/mL) F (%) iv (0.3 mg/kg) 5.8 2.4 88 156 162 po (1 mg/kg) 6.5 3.1 105 340 352 65 |
| References |
[1]. Discovery of N-(2-benzyl-4-oxochroman-7-yl)-2-(5-(ethylsulfonyl) pyridin-2-yl) acetamide (b12) as a potent, selective, and orally available novel retinoic acid receptor-related orphan receptor γt inverse agonist. Bioorg Chem. 2022 Feb;119. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1527 mL | 10.7636 mL | 21.5271 mL | |
| 5 mM | 0.4305 mL | 2.1527 mL | 4.3054 mL | |
| 10 mM | 0.2153 mL | 1.0764 mL | 2.1527 mL |